Scaling Behaviors of Graphene Nanoribbon FETs A Three Dimensional Quantum Simulation Study

BRIEF COMMUNICATIONRheological behaviour of ethylene glycol-titanate nanotube nanofluidsHaisheng Chen ÆYulong Ding ÆAlexei Lapkin ÆXiaolei FanReceived:11July 2008/Accepted:4February 2009/Published online:26February 2009ÓSpringer Science+Business Media B.V.2009Abstract Experimental work has been performed on the rheological behaviour of ethylene glycol based nanofluids containing titanate nanotubes over 20–60°C and a particle mass concentration of 0–8%.It is found that the nanofluids show shear-thinning behaviour particularly at particle concentrations in excess of *2%.Temperature imposes a very strong effect on the rheological behaviour of the nanofluids with higher temperatures giving stronger shear thinning.For a given particle concentration,there exists a certain shear rate below which the viscosity increases with increasing temperature,whereas the reverse occurs above such a shear rate.The normalised high-shear viscosity with respect to the base liquid viscosity,however,is independent of temperature.Further analyses suggest that the temperature effects are due to the shear-dependence of the relative contributions to the viscosity of the Brownian diffusion and convection.The analyses also suggest that a combination of particle aggregation and particle shape effects is the mechanism for the observed high-shear rheological behaviour,which is also supported by the thermal conductivity measure-ments and analyses.Keywords Rheological behaviour ÁEthylene glycol ÁTitanate nanotube ÁNanofluid ÁThermal conductivityNanofluids are dilute suspensions of particles with at least one dimension smaller than about 100nm (Choi 1995).Such a type of materials can be regarded as functionalized colloids with special requirements of a low-particle loading,a high-thermal performance,favourable flow/rheolgocial behaviour,and a great physical and chemical stability over a wide range of process and solution chemistry conditions.Nano-fluids have been shown to be able to enhance heat transfer (Choi 1995;Wang and Mujumdar.2007),mass transfer (Krishnamurthy et al.2006),and wetting and spreading (Wasan and Nikolov 2003),and have been a hot topic of research over the past decade (Wang and Mujumdar 2007;Keblinski et al.2005).Most published studies have focused on the heat transfer behaviour including thermal conduction (Choi 1995;Wang et al.1999;Wang and Mujumdar 2007;Keblinski et al.2005;Eastman et al.2001;He et al.2007;Ding et al.2006),phase change (boiling)heat transfer (Das et al.2003;Pak and Cho 1998),and convective heat transfer (Wang and Mujumdar 2007;Keblinski et al.2005;He et al.2007;Ding et al.2006,Chen et al.2008;Prasher et al.2006a and Yang et al.2005).Only few studies have been devoted to the rheological behaviour ofH.Chen ÁY.Ding (&)Institute of Particle Science and Engineering,University of Leeds,Leeds,UK e-mail:y.ding@pkin ÁX.FanDepartment of Chemical Engineering,University of Bath,Bath,UKJ Nanopart Res (2009)11:1513–1520DOI 10.1007/s11051-009-9599-9nanofluids(He et al.2007;Chen et al.2008;Prasher et al.2006a,b;Kwak and Kim2005;Lee et al.2006), although there is a large body of literature on suspensions rheology;see for example,Russel et al. (1991);Chow(1993);Petrie(1999),Larson(1999); Goodwin et al.(2000)l;Mohraz et al.(2004);Larson (2005);Egres and Wagner(2005);Abdulagatov and Azizov(2006).Particularly,there is little in the literature on the effect of temperature on the rheo-logical behaviour of nanofluids.Clearly,there is a gap in the current rheological literature for this type offluids.Furthermore,recent work has shown that the thermal behaviour of nanofluids correlates well with their rheological behaviour(Prasher et al.2006a, b;Chen et al.2007a;Abdulagatov and Azizov2006). In a recent study,we investigated systemically the rheological behaviour of ethylene glycol(EG)based spherical TiO2nanofluids(Chen et al.2007b).The results show that the nanofluids are Newtonian over a shear rate range of0.5–104s-1and the shear viscosity is a strong function of temperature,particle concentration and aggregation microstructure.This work is concerned about the rheological behaviour of EG based nanofluids containing titanate nanotubes (TNT).The specific objectives of the work are to investigate the effects of particle shape,particle concentration and temperature on nanofluids viscosity, and to understand the relationship between the rheo-logical behaviour and the effective thermal conductivity of nanofluids.It is for thefirst time that the rheological behaviour of a highly viscous EG based TNT nanofluids is investigated in a systematic manner.As will be seen later,the results of this work provide further evidence that the rheological measure-ments could provide information of particle structuring for predicting the effective thermal conductivity of nanofluids.The EG-TNT nanofluids used in this work were formulated by using the so-called two-step method with EG purchased from Alfa Aesar and TNT synthesized in our labs using a method described elsewhere(Bavykin et al.2004).The details of nanofluids formulation can be found elsewhere(Wen and Ding2005;He et al.2007;Chen et al.2007b). The TNT particles have a diameter(b)of*10nm and a length(L)of*100nm,giving an aspect ratio of(r=L/b)of*10.To avoid complications in interpreting the experimental results,no dispersants/ surfactants were used in the formulation.The nanofluids formulated were found stable for over 2months.The rheological behaviour of the nano-fluids was measured by using a Bolin CVO rheometer (Malvern Instruments,UK)over a shear rate range of 0.03–3,000s-1,a nanoparticle mass concentration of w=0–8%,and a temperature range of20–60°C (293–333K).The nanofluids were characterised for their size by using a Malvern Nanosizer(Malvern Instruments,UK)and a scanning electron microscope (SEM).The average effective particle diameter was found to be*260nm for all nanofluids formulated. This size is much larger than the equivalent diameter of the primary nanoparticles due to aggregation;see later for more discussion.Note that the particle size characterisation was performed both before and after the rheological measurements and no detectable changes to particle size were found.Figure1shows the viscosity of pure EG and EG-TNT nanofluids as a function of shear rate at 40°C.The results at other temperatures are similar.It can be seen that the EG-TNT nanofluids exhibit highly shear-thinning behaviour particularly when the TNT concentration exceeds*2%.Such behaviour is different from the observed Newtonian behaviour of EG-TiO2nanofluids containing spherical nanoparti-cles over similar shear rate range(Chen et al.2007b) where the base liquid,EG,is the same as that used in the current wok.The behaviour is similar to the observations of carbon nanotube nanofluids(Ding et al.2006)and CuO nanorod nanofluids(Kwak and Kim2005),although there are important differencesbetween them such as temperature dependence as will be discussed later.The shear-thinning behaviour of well-dispersed suspensions can be interpreted by the structuring of interacting particles(Doi and Edwards1978a,b and Larson1999).In a quiescent state,a rod-like particle has three types of motion due to Brownian diffusion: rotational(end-over-end)motion around the mid-point and translational motion in parallel or perpendicular to the long axis.For dilute suspensions with a number density,c,ranging between0and1/L3or volume fraction,u,ranging between0and1/r2),the average spacing between the particles is larger than the longest dimension of the rod,and zero shear viscosity can be approximated by gð0Þ%g0ð1þAÁcL3Þwith g0the base liquid viscosity and A,a numerical constant(Doi and Edwards1978a).For suspensions with 1/L3\c\1/bL2or1/r2\f/\1/r,the rod-like particles start to interact.The rotational motion is severely restricted,as well as the translational motion perpendicular to the long axis,and the zero shear viscosity can be estimated by gð0Þ%g0ð1þðBcL3Þ3Þ; with B a numerical constant(Doi and Edwards1978b). As a consequence,the zero shear viscosity can be much greater than the base liquid viscosity.The large viscosity is due to the rod-like shape effect and the viscosity is very sensitive to shear,which tends to align particles and hence the shear-thinning behaviour as shown in Fig.1.Note that the above mechanism can give a qualitative explanation for the experimental observations at low-shear rates and the shear-thinning behaviour as shown in Fig.1,it does not explain the high-shear viscosity of the nanofluids,which will be discussed later.It should also be noted that the criteria for classifying nanofluids given above need to be modified due to the presence of aggregates;see later for more discussion.Figure2shows the shear viscosity of4.0%EG-TNT nanofluids as a function of shear rate at different temperatures.The results under other concentrations are similar.It can be seen that the temperature has a very strong effect on the rheological behaviour of nanofluids with higher temperatures giving stronger shear thinning.For shear rates below*10s-1,the shear viscosity increases with increasing temperature, whereas the trend is reversed when the shear rate is above*10s-1.As mentioned above,this behaviour was not observed for carbon nanotube(Ding et al. 2006)and CuO nanorod(Kwak and Kim2005)nanofluids and we have not seen reports on such behaviour for nanofluids in the literature;see later for more discussion on the underlying mechanisms. Figure2also shows that the strongest shear thinning occurs at40–60°C,whereas very weak-shear thinning takes places at20–30°C.It is also noted that the shear viscosity of nanofluids at all temperatures investigated approaches a constant at high-shear rates.If the high-shear viscosity is plotted against temperature,Fig.3is obtained where the shear rate corresponding to the high-shear viscosity is taken as *2,000s-1.An inspection of all the data indicates that theyfit the following equation very well:ln g¼AþBÂ1000=TþCðÞð1Þwhere g is the shear viscosity(mPaÁs),T is the absolute temperature(K),and A,B and C areconstants given in Table1.Equation(1)takes a similar format as that widely used for liquid viscosity (Bird et al.2002)and for EG based nanofluids containing spherical particles(Chen et al.2007b).If the measured high-shear viscosity is normalized with respect to the shear viscosity of the base liquid, the relative increaseðg i¼ðgÀg0Þ=g0Þof the high-shear viscosity is found to be only a function of concentration but independent of temperature over the temperature range investigated in this work.The relative increments in the shear viscosities of nano-fluids containing0.5%,1.0%,2.0%,4.0%and8.0% particles are 3.30%,7.00%,16.22%,26.34%and 70.96%,respectively.Similar temperature indepen-dence of the shear viscosity was also observed for EG-TiO2and water-TiO2nanofluids containing spherical nanoparticles(Chen et al.2007b).The experimentally observed temperature depen-dence can be interpreted as follows.Given the base liquid and nanoparticles,the functional dependence of viscosity on shear rate is determined by the relative importance of the Brownian diffusion and convection effects.At temperatures below*30°C,the contribu-tion from the Brownian diffusion is weak due to high-base liquid viscosity.As a consequence,the shear dependence of the suspension is weak(Fig.2).The contribution from the Brownian diffusion becomes increasingly important with increasing temperature particularly above40°C due to the exponential dependence of the base liquid viscosity on temperature (Fig.3).At very high-shear rates,the Brownian diffusion plays a negligible role in comparison with the convective contribution and hence independent of the high-shear viscosity on the temperature.We now start to examine if the classical theories for the high-shear viscosity predict the experimental measurements(note that there is a lack of adequate theories for predicting the low shear viscosity).Figure4shows the shear viscosity increment as a function of nanoparticle volume concentration together with the predictions by the following Brenner &Condiff Equation for dilute suspensions containing large aspect ratio rod-like particles(Brenner and Condiff1974):g¼g01þg½ uþO u2ÀÁÀÁð2Þwhere the intrinsic viscosity,½g ;for high-shear rates has the following form(Goodwin and Hughes2000):½g ¼0:312rln2rÀ1:5þ2À0:5ln2rÀ1:5À1:872rð3ÞAlso included in Fig.4are the data for EG-TiO2 nanofluids with spherical nanoparticles(Chen et al. 2007b)and predictions by the Einstein Equation (Einstein1906,1911)for dilute non-interacting suspensions of spherical particles,g¼g01þ2:5uðÞ: It can be seen that both the Einstein and Brenner& Condiff equations greatly underpredict the measured data for the EG-TNT nanofluids.The high-shear viscosity of EG-TNT nanofluids is much higher than that of the EG-TiO2nanofluids containing spherical nanoparticles,indicating a strong particle shape effect on the shear viscosity of nanofluids.Although the shear-thinning behaviour of the nanofluids could be partially attributed to the structuring of interacting rod-like particles,the large deviation between the measured high-shear viscosity and the predicted ones by the Brenner&Condiff equation cannot fully be interpreted.In the following,an attempt is made to explain the experimental observations from the viewpoint of aggregation of nanaoparticles,which have been shown to play a key role in thermal behaviour of nanofluids in recent studies(Wang et al. 2003;Xuan et al.2003;Nan et al.1997;Prasher et al. 2006a,b;Keblinski et al.2005).Such an approach is also supported by the SEM and dynamic lightTable1Empirical constants for Eq.(1)a Maximum discrepancies;b Minimum discrepancies Concentration(wt%)A B C MaxD a(%)MinD b(%)0.0-3.21140.86973-154.570.62-1.440.5-3.42790.94425-148.490.93-0.471.0-2.94780.81435-159.14 1.11-0.692.0-2.2930.65293-174.57 1.64-0.694.0-2.63750.7574-165.820.99-0.948.0-2.73140.93156-145.010.88-1.57scattering analyses,which,as mentioned before, show clear evidence of particle aggregation.According to the modified Krieger-Dougherty equation(Goodwin and Hughes2000;Wang et al. 2003;Xuan et al.2003;Nan et al.1997),the relative viscosity of nanofluids,g r,is given as:g r¼1Àu a=u mðÞÀ½g u mð4Þwhere u m is the maximum concentration at which the flow can occur and u a is the effective volume fraction of aggregates given by u a¼u=u ma with u ma the maximum packing fraction of aggregates.As aggre-gates do not have constant packing throughout the structure,the packing density is assumed to change with radial position according to the power law with a constant index(D).As a result,u a is given as u a¼uða a=aÞ3ÀD;with a a and a,the effective radii of aggregates and primary nanoparticles,respectively. The term D is also referred as the fractal index meaning the extent of changes in the packing fraction from the centre to the edge of the aggregates.Typical values of D are given in normal textbook as D= 1.8–2.5for diffusion limited aggregation(DLA)and D=2.0–2.2for reaction limited aggregation(RLA); see for example Goodwin and Hughes(2000).For nanofluids containing spherical nanoparticles,the value of D has been shown experimentally and numerically to be between1.6and1.8(Wang et al. 2003,Xuan et al.2003)and between1.8and2.3, respectively(Waite et al.2001).A typical value of 1.8is suggested for nanofluids made of spherical nanoparticles(Prasher et al.2006a,b).However,little research has been found on the fractal index for nanofluids containing rod-like nanoparticles.The colloid science literature suggests a fractal index of 1.5–2.45for colloidal suspensions depending on the type of aggregation,chemistry environment,particle size and shape and shearflow conditions(Haas et al. 1993;Mohraz et al.2004;Hobbie and Fry2006; Micali et al.2006;Lin et al.2007).In a recent study, Mohraz et al.(2004)investigated the effect of monomer geometry on the fractal structure of colloi-dal rod aggregates.They found that the fractal index is a non-linear function of the monomer aspect ratio with the D increasing from*1.80to*2.3when the aspect ratio of the rod-like nanoparticles increases from1.0to30.6.Based on the above,a value of D=2.1is taken for nanofluids used in this work (Mohraz et al.2004,Lin et al.2007).Although the fractal model may appear to simplify the complexity of microstructures in aggregating systems containing rod-like particles,excellent agreement between the model prediction and experimental measurements exists when a a/a=9.46;see Fig.4.Here the aggregates are assumed to formflow units of an ellipsoidal shape with an effective aspect ratio of r a¼L a=b a;where L a and b a are the effective length and diameter,respectively.In the calculation,a typical value of u m of0.3is taken(Barnes et al.1989),and the intrinsic viscosity[g]is calculated by Eq.(3).It is to be noted that the aggregate size thatfits well to the rheological data(Fig.4)is consistent with the particle size analyses using both the SEM and the Malvern Nanosizer.A comparison between the EG-TNT data (a a/a=9.46,D=2.1,u m=0.30)and the EG-TiO2 data(a a/a=3.34,D=1.8,u m=0.605)(Chen et al. 2007b)in Fig.4suggests that the larger aggregate size in TNT nanofluids be an important factor responsible for the stronger shear-thinning behaviour and higher shear viscosity of TNT nanofluids.An inspection of Eq.(4)indicates that the effec-tive volume fraction u a u a¼u a a=aðÞ3ÀDis much higher than the actual volume fraction(u).This leads to the experimentally observed high-shear viscosity even for very dilute nanofluids,according to the classification discussed before.As a consequence,the demarcations defining the dilute and semi-concen-trated dispersions should be changed by using the effective volume fraction.The model discussed above can also provide a macroscopic explanation for the temperature indepen-dence of the high-shear viscosity.From Eq.(4),one can see that the relative high-shear viscosity depends on three parameters,the maximum volume fraction, u m,the effective volume fraction,u a and the intrinsic viscosity,[g].For a given nanofluid at a temperature not far from the ambient temperature,the three parameters are independent of temperature and hence the little temperature dependence of the relative shear viscosity.Microscopically,as explained before,the temperature-independent behaviour is due to negligi-ble Brownian diffusion compared with convection in high-shearflows.To further illustrate if the proposed aggregation mechanism is adequate,it is used to predict the effective thermal conductivity of the nanofluids by using the following conventional Hamilton–Crosser model(H–C model)(Hamilton and Crosser1962):k=k0¼k pþðnÀ1Þk0ÀðnÀ1Þuðk0Àk pÞk pþðnÀ1Þk0þuðk0Àk pÞð5Þwhere k and k0are,respectively,the thermal conductivities of nanofluids and base liquid,n is the shape factor given by n=3/w with w the surface area based sphericity.For TNT used in this work,the sphericity w is estimated as0.6(Hamilton and Crosser1962).For suspensions of aggregates,the above equation takes the following form:k=k0¼k aþðnÀ1Þk0ÀðnÀ1Þu aðk0Àk aÞa0a0að6Þwhere k a is the thermal conductivity of aggregates.To calculate k a,Eq.(6)is combined with the following Nan’s model(Nan et al.2003)for randomly dispersed nanotube-based composites:k a=k0¼3þu in½2b xð1ÀL xÞþb zð1ÀL zÞ3Àu in½2b x L xþb z L zð7Þwhere/in is the solid volume fraction of aggregates, b x¼ðk xÀk0Þ=½k mþL xðk tÀk mÞ and b z¼ðk zÀk0Þ=½k mþL zðk tÀk mÞ with k x,k m and k t being the thermal conductivities of nanotubes along trans-verse and longitudinal directions and isotropic thermal conductivity of the nanotube,respectively. In this work,k x,k m and k t are taken the same value as k p for afirst order of approximation due to lack of experimental data,and L x and L z are geometrical factors dependent on the nanotube aspect ratio given by L x¼0:5r2=ðr2À1ÞÀ0:5r coshÀ1r=ðr2À1Þ3=2 and L z¼1À2L x:Figure5shows the experimental results together with predictions by the original H–C model(Eq.5) and revised H–C model(Eq.6).Here the experiment data were obtained using a KD2thermal property meter(Labcell,UK)(Murshed et al.2005;Chen et al. 2008).One can see that the measured thermal conductivity is much higher than the prediction by the conventional H–C model(Eq.5),whereas the modified H–C model taking into account the effect of aggregation(Eq.6)agrees very well with the exper-imental data.The above results suggest that nanoparticle aggregates play a key role in the enhancement of thermal conductivity of nanofluids. The results also suggest that one could use the rheology data,which contain information of particle structuring in suspensions,for the effective thermal conductivity prediction.In summary,we have shown that EG-TNT nano-fluids are non-Newtonian exhibiting shear-thinning behaviour over20–60°C and a particle mass concen-tration range of0–8%,in contrast to the Newtonian behaviour for EG-TiO2nanofluids containing spher-ical particles.The non-Newtonian shear-thinning behaviour becomes stronger at higher temperatures or higher concentrations.For a given particle concen-tration,there exists a certain shear rate(e.g.*10s-1 for4wt%)below which the viscosity increases with increasing temperature,whereas the reverse occurs above such a shear rate.The normalised high-shearviscosity with respect to the base liquid viscosity, however,is found to be independent of temperature. These observations have not been reported in the literature for nanofluids.Further analyses suggest that the temperature effects are due to the shear-depen-dence of the relative contributions to the viscosity of the Brownian diffusion and convection.The analyses also suggest that a combination of particle aggregation and particle shape effects is the mechanism for the observed high-shear rheological behaviour,which is supported not only by the particle size measurements but also by the thermal conductivity measurements and analyses using a combination of the H–C and Nan’s models.The results of this work also indicate that one could use the information of aggregation from the rheological experiments for predicting the effec-tive thermal conductivity of nanofluids. Acknowledgement The work was partially supported by UK EPSRC under grants EP/E00041X/1and EP/F015380/1.ReferencesAbdulagatov MI,Azizov ND(2006)Experimental study of the effect of temperature,pressure and concentration on the viscosity of aqueous NaBr solutions.J Solut Chem 35(5):705–738.doi:10.1007/s10953-006-9020-6Barnes HA,Hutton JF,Walters K(1989)An introduction to rheology.Elsevier Science B.V.,NetherlandsBavykin DV,Parmon VN,Lapkin AA,Walsh FC(2004)The effect of hydrothermal conditions on the mesoporous struc-ture of TiO2nanotubes.J Mater Chem14(22):3370–3377 Bird RB,Steward WE and Lightfoot EN(2002)Transport Phenomena,2nd edn.Wiley,New YorkBrenner H,Condiff DW(1974)Transport mechanics in sys-tems of orientable particles,Part IV.Convective Transprort.J Colloid Inter Sci47(1):199–264Chen HS,Ding YL,He YR,Tan CQ(2007a)Rheological behaviour of ethylene glycol based titania nanofluids.Chem Phys Lett444(4–6):333–337Chen HS,Ding YL,Tan CQ(2007b)Rheological behaviour of nanofluids.New J Phys9(367):1–25Chen HS,Yang W,He YR,Ding YL,Zhang LL,Tan CQ,Lapkin AA,Bavykin DV(2008)Heat transfer andflow behaviour of aqueous suspensions of titanate nanotubes under the laminar flow conditions.Powder Technol183:63–72Choi SUS(1995)Enhancing thermal conductivity offluids with nanoparticles In:Siginer DA,Wang HP(eds) Developments applications of non-newtonianflows,FED-vol231/MD-vol66.ASME,New York,pp99–105 Chow TS(1993)Viscosities of concentrated dispersions.Phys Rev E48:1977–1983Das SK,Putra N,Roetzel W(2003)Pool boiling characteristics of nano-fluids.Int J Heat Mass Transfer46:851–862Ding YL,Alias H,Wen DS,Williams RA(2006)Heat transfer of aqueous suspensions of carbon nanotubes(CNT nanofluids).Int J Heat Mass Transf49(1–2):240–250 Doi M,Edwards SF(1978a)Dynamics of rod-like macro-molecules in concentrated solution,Part1.J Colloid Sci 74:560–570Doi M,Edwards SF(1978b)Dynamics of rod-like macro-molecules in concentrated solution,Part2.J Colloid Sci 74:918–932Eastman JA,Choi SUS,Li S,Yu W,Thompson LJ(2001) Anomalously increased effective thermal conductivities of ethylene glycol-based nanofluids containing copper nanoparticles.Appl Phys Lett78:718–720Egres RG,Wagner NJ(2005)The rheology and microstructure of acicular precipitated calcium carbonate colloidal sus-pensions through the shear thickening transition.J Rheol 49:719–746Einstein A(1906)Eine neue Bestimmung der Molekul-dimension(a new determination of the molecular dimensions).Annal der Phys19(2):289–306Einstein A(1911)Berichtigung zu meiner Arbeit:Eine neue Bestimmung der Molekul-dimension(correction of my work:a new determination of the molecular dimensions).Ann der Phys34(3):591–592Goodwin JW,Hughes RW(2000)Rheology for chemists—an introduction.The Royal Society of Chemistry,UK Haas W,Zrinyi M,Kilian HG,Heise B(1993)Structural analysis of anisometric colloidal iron(III)-hydroxide par-ticles and particle-aggregates incorporated in poly(vinyl-acetate)networks.Colloid Polym Sci271:1024–1034 Hamilton RL,Crosser OK(1962)Thermal Conductivity of heterogeneous two-component systems.I&EC Fundam 125(3):187–191He YR,Jin Y,Chen HS,Ding YL,Cang DQ(2007)Heat transfer andflow behaviour of aqueous suspensions of TiO2nanoparticles(nanofluids)flowing upward through a vertical pipe.Int J Heat Mass Transf50(11–12):2272–2281Hobbie EK,Fry DJ(2006)Nonequilibrium phase diagram of sticky nanotube suspensions.Phys Rev Lett97:036101 Keblinski P,Eastman JA and Cahill DG(2005)Nanofluids for thermal transport,Mater Today,June Issue,36–44 Krishnamurthy S,Lhattacharya P,Phelan PE,Prasher RS (2006)Enhanced mass transport of in nanofluids.Nano Lett6(3):419–423Kwak K,Kim C(2005)Viscosity and thermal conductivity of copper oxide nanofluid dispersed in ethylene glycol.Korea-Aust Rheol J17(2):35–40Larson RG(1999)The structure and rheology of complex fluids.Oxford University Press,New YorkLarson RG(2005)The rheology of dilute solutions offlexible polymers:progress and problems.J Rheol49:1–70Lee D,Kim J,Kim B(2006)A new parameter to control heat transport in nanofluids:surface charge state of the particle in suspension.J Phys Chem B110:4323–4328Lin JM,Lin TL,Jeng U,Zhong Y,Yeh C,Chen T(2007) Fractal aggregates of fractal aggregates of the Pt nano-particles synthesized by the polyol process and poly(N-vinyl-2-pyrrolidone)reduction.J Appl Crystallogr40: s540–s543Micali N,Villari V,Castriciano MA,Romeo A,Scolaro LM (2006)From fractal to nanorod porphyrin J-aggregates.Concentration-induced tuning of the aggregate size.J Phys Chem B110:8289–8295Mohraz A,Moler DB,Ziff RM,Solomon MJ(2004)Effect of monomer geometry on the fractal structure of colloidal rod aggregates.Phys Rev Lett92:155503Murshed SMS,Leong KC,Yang C(2005)Enhanced thermal conductivity of TiO2-water based nanofluids.Int J Therm Sci44:367–373Nan CW,Birringer R,Clarke DR,Gleiter H(1997)Effective thermal conductivity of particulate composites with inter-facial thermal resistance.J Appl Phys81(10):6692–6699 Nan CW,Shi Z,Lin Y(2003)A simple model for thermal conductivity of carbon nanotube-based composites.Chem Phys Lett375(5–6):666–669Pak BC,Cho YI(1998)Hydrodynamic and heat transfer study of dispersedfluids with submicron metallic oxide parti-cles.Exp Heat Transf11:150–170Prasher R,Song D,Wang J(2006a)Measurements of nanofluid viscosity and its implications for thermal applications.Appl Phys Lett89:133108-1-3Prasher R,Phelan PE,Bhattacharya P(2006b)Effect of aggregation kinetics on thermal conductivity of nanoscale colloidal solutions(nanofluids).Nano Lett6(7):1529–1534Russel WB,Saville DA,Scholwater WR(1991)Colloidal dispersions.Cambridge University Press,Cambridge Waite TD,Cleaver JK,Beattie JK(2001)Aggregation kinetics and fractal structure of gamma-alumina assemblages.J Colloid Interface Sci241:333–339Wang XQ,Mujumdar AS(2007)Heat transfer characteristics of nanofluids:a review.Int J Therm Sci46:1–19Wang XW,Xu XF,Choi SUS(1999)Thermal conductivity of nanoparticle–fluid mixture.J Thermphys Heat Transf 13:474Wang BX,Zhou LP,Peng XF(2003)A fractal model for predicting the effective thermal conductivity of liquid with suspension of nanoparticles.Int J Heat Mass Transf 46:2665–2672Wasan DT,Nikolov AD(2003)Spreading of nanofluids on solids.Nature423(6936):156–159Wen DS,Ding YL(2005)Formulation of nanofluids for natural convective heat transfer applications.Int J Heat Fluid Flow26:855–864Xuan YM,Li Q,Hu J,WF(2003)Aggregation structure and thermal conductivity of nanofluids.AIChE J49(4):1038–1043Yang Y,Zhong ZG,Grulke EA,Anderson WB,Wu G(2005) Heat transfer properties of nanoparticle-in-fluid dispersion (nanofluids)in laminarflow.Int J Heat Mass Transf 48:1107–1116。

FAPα靶向标记化合物131I-FAPI-03的合成及初步体内外实验研究马　欢1,2, 廖家莉2, 杨远友2, 刘　宁2, 李飞泽2（1. 四川省医学科学院 四川省人民医院（电子科技大学附属医院） 核医学科，成都　610072；2. 四川大学 原子核科学技术研究所，辐射物理及技术教育部重点实验室，成都　610064）摘要：本研究以4-喹啉基-甘氨基-2-氰基吡咯烷为骨架，对连接基团进行碳链延长及羟基修饰成功合成FAPI 衍生物ATE-FAPI-03；通过亲电取代反应实现其131I 标记，并对标记化合物131I-FAPI-03的脂水分配比、体外稳定性等进行分析；开展细胞结合、内吞、流出等实验以评价131I-FAPI-03的体外动力学特征；并考察了131I-FAPI-03在荷胶质瘤小鼠体内的分布情况。

结果表明：131I-FAPI-03为亲脂性小分子，并具有良好的体外稳定性；与FAPα阳性细胞U87MG 孵育10 min 时的结合率为（22.00 ± 0.35）%，且随着孵育时间的延长结合率有明显的上升趋势，而与FAPα阴性细胞MCF-7的结合率始终处于较低水平；通过竞争结合实验测得131I-FAPI-03的IC 50值为45.5 nM ，表明其对FAPα具有较高的亲和力；大部分与U87MG 细胞结合的131I-FAPI-03可被细胞内吞，但其在细胞中的滞留能力偏低。

131I-FAPI-03在荷胶质瘤小鼠体内具有快速的肿瘤靶向能力：经尾静脉注射5 min 后，肿瘤组织对131I-FAPI-03的放射性摄取值为（14.90 ±3.21）% ID/g ，注射2 h 后，肿瘤/肌肉的放射性摄取比值达到（43.7 ± 16.7）。

上述结果为新型FAPα靶向药物的研发提供了重要的参考。

关键词：FAPα；131I ；FAPI ；胶质瘤中图分类号：TL92+3 文献标志码：A 文章编号：1000-7512(2024)02-0097-09doi ：10.7538/tws.2024.37.02.0097Synthesis and Preliminary Evaluation of FAPα Targeted Tracer 131I-FAPI-03MA Huan 1,2, LIAO Jiali 2, YANG Yuanyou 2, LIU Ning 2, LI Feize2（1. Department of Nuclear Medicine , Sichuan Provincial People’s Hospital ,University of Electronic Science and Technology of China , Chengdu 610072, China ;2. Key Laboratory of Radiation Physics and Technology of the Ministry of Education ,Institute of Nuclear Science and Technology , Sichuan University , Chengdu 610064, China ）Abstract: Using N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) as scaffold ，we prolonged the linker with serine to obtain a FAPI derivative ATE-FAPI-03，which was subsequently labeled with131I byelectrophilic substitution. Then the in vitro stability ，Log P value ，binding affinity ，targeting properties and biodistribution behavior of 131I-FAPI-03 was evaluated. Results show that 131I-FAPI-03 was lipophilic and stable in vitro ，capable of specifically binding to FAPα-positive U87MG cells收稿日期：2023-12-04；修回日期：2024-01-18基金项目：中央高校基本科研业务费专项资金资助（2023SCU12132）；四川省医学科学院.四川省人民医院青年人才基金（2022QN32）通信作者：李飞泽第37卷 第2期同 位 素Vol. 37 No. 22024年 4 月Journal of IsotopesApr. 2024fast with a major proportion trapped intracellularly. After 10 min of incubation，131I-FAPI-03 showed a specific binding rate of (22.00 ± 0.35)%，and the binding rate increased with the incubation time，to a peak of (37.5 ± 0.83)% at 180 min. However，the FAPα-negative MCF-7 cells exhibited very low uptake of 131I-FAPI-03 at any time point. The IC50 measured by the competition assay indicated significant binding property of 131I-FAPI-03. Biodistribution studies revealed that 131I-FAPI-03 could rapidly accumulate in tumor sites with an uptake of (14.90 ± 3.21)% ID/g at 5 min post injection. At 2 h post injection，131I-FAPI-03 displayed the highest tumor-to-muscle ratio of 43.7 ± 16.7. All above results provided important reference for the development of novel FAPα-targeting tracers.Key words: FAPα; 131I; FAPI; glioma肿瘤相关成纤维细胞（CAF）作为肿瘤微环境的主要组成部分，积极参与细胞外基质结构的重塑、肿瘤侵袭与转移、免疫抑制和耐药生成过程[1-3]。

纳米纺织材料课题组[1] ZHOU H, NAEEM M A, LV P, et al. Effect Effect of pore distribution on the lithium storage properties of porous C/SnO2 nanofibers [J]. Journal of Alloys and Compounds, 2017, 711(414-23.[2] ZHANG J, YANG Q, CAI Y, et al. Fabrication and characterization of electrospun porous cellulose acetate nanofibrous mats incorporated with capric acid as form-stable phase change materials for storing/retrieving thermal energy [J]. International Journal of Green Energy, 2017, 14(12): 1011-9.[3] ZHANG J, HOU X, PANG Z, et al. Fabrication of hierarchical TiO2 nanofibers by microemulsion electrospinning for photocatalysis applications [J]. Ceramics International, 2017, 43(17): 15911-7.[4] ZHANG J, CAI Y, HOU X, et al. Fabrication of hierarchically porous TiO2 nanofibers by microemulsion electrospinning and their application as anode material for lithium-ion batteries [J]. Beilstein Journal of Nanotechnology, 2017, 8(1297-306.[5] ZHANG J, CAI Y, HOU X, et al. Fabrication and Characterization of Porous Cellulose Acetate Films by Breath Figure Incorporated with Capric Acid as Form-stable Phase Change Materials for Storing/Retrieving Thermal Energy [J]. Fibers and Polymers, 2017, 18(2): 253-63.[6] YUAN X, XU W, HUANG F, et al. Structural colors of fabric from Ag/TiO2 composite films prepared by magnetron sputtering deposition [J]. International Journal of Clothing Science and Technology, 2017, 29(3): 427-35.[7] SHAO D, GAO Y, CAO K, et al. Rapid surface functionalization of cotton fabrics by modified hydrothermalsynthesis of ZnO [J]. Journal of the Textile Institute, 2017, 108(8): 1391-7.[8] SHA S, JIANG G, CHAPMAN L P, et al. Fast Penetration Resolving for Weft Knitted Fabric Based on Collision Detection [J]. Journal of Engineered Fibers and Fabrics, 2017, 12(1): 50-8.[9] QIAO H, XIA Z, LIU Y, et al. Sonochemical synthesis and high lithium storage properties of ordered Co/CMK-3 nanocomposites [J]. Applied Surface Science, 2017, 400(492-7.[10] QIAO H, XIA Z, FEI Y, et al. Electrospinning combined with hydrothermal synthesis and lithium storage properties of ZnFe2O4-graphene composite nanofibers [J]. Ceramics International, 2017, 43(2): 2136-42.[11] PANG Z, NIE Q, YANG J, et al. Ammonia sensing properties of different polyaniline-based composite nanofibres [J]. Indian Journal of Fibre & Textile Research, 2017, 42(2): 138-44.[12] PANG Z, NIE Q, WEI A, et al. Effect of In2O3 nanofiber structure on the ammonia sensing performances of In2O3/PANI composite nanofibers [J]. Journal of Materials Science, 2017, 52(2): 686-95.[13] PANG Z, NIE Q, LV P, et al. Design of flexible PANI-coated CuO-TiO2-SiO2 heterostructure nanofibers with high ammonia sensing response values [J]. Nanotechnology, 2017, 28(22):[14] LV X, LI G, LI D, et al. A new method to prepare no-binder, integral electrodes-separator, asymmetric all-solid-state flexible supercapacitor derived from bacterial cellulose [J]. Journal of Physics and Chemistry of Solids, 2017, 110(202-10.[15] LV P, YAO Y, ZHOU H, et al. Synthesis of novel nitrogen-doped carbon dots for highly selective detection of iron ion [J]. Nanotechnology, 2017, 28(16):[16] LV P, YAO Y, LI D, et al. Self-assembly of nitrogen-dopedcarbon dots anchored on bacterial cellulose and their application in iron ion detection [J]. Carbohydrate Polymers, 2017, 172(93-101.[17] LUO L, QIAO H, XU W, et al. Tin nanoparticles embedded in ordered mesoporous carbon as high-performance anode for sodium-ion batteries [J]. Journal of Solid State Electrochemistry, 2017, 21(5): 1385-95.[18] LUO L, LI D, ZANG J, et al. Carbon-Coated Magnesium Ferrite Nanofibers for Lithium-Ion Battery Anodes with Enhanced Cycling Performance [J]. Energy Technology, 2017, 5(8): 1364-72.[19] LU H, WANG Q, LI G, et al. Electrospun water-stable zein/ethyl cellulose composite nanofiber and its drug release properties [J]. Materials Science & Engineering C-Materials for Biological Applications, 2017, 74(86-93.[20] LI G, NANDGAONKAR A G, WANG Q, et al. Laccase-immobilized bacterial cellulose/TiO2 functionalized composite membranes: Evaluation for photo- and bio-catalytic dye degradation [J]. Journal of Membrane Science, 2017, 525(89-98.[21] LI G, NANDGAONKAR A G, HABIBI Y, et al. An environmentally benign approach to achieving vectorial alignment and high microporosity in bacterial cellulose/chitosan scaffolds [J]. Rsc Advances, 2017, 7(23): 13678-88.[22] LI G, NANDGAONKAR A G, HABIBI Y, et al. An environmentally benign approach to achieving vectorial alignment and high microporosity in bacterial cellulose/chitosan scaffolds (vol 7, pg 13678, 2017) [J]. Rsc Advances, 2017, 7(27): 16737-.[23] HUANG X, MENG L, WEI Q, et al. Effect of substrate structures on the morphology and interfacial bonding properties of copper films sputtered on polyester fabrics [J]. InternationalJournal of Clothing Science and Technology, 2017, 29(1): 39-46.[24] CAI Y, SONG X, LIU M, et al. Flexible cellulose acetate nano-felts absorbed with capric-myristic-stearic acid ternary eutectic mixture as form-stable phase-change materials for thermal energy storage/retrieval [J]. Journal of Thermal Analysis and Calorimetry, 2017, 128(2): 661-73.[25] CAI Y, HOU X, WANG W, et al. Effects of SiO2 nanoparticles on structure and property of form-stable phase change materials made of cellulose acetate phase inversion membrane absorbed with capric-myristic-stearic acid ternary eutectic mixture [J]. Thermochimica Acta, 2017, 653(49-58.[26] ZHOU J, WANG Q, LU H, et al. Preparation and Characterization of Electrospun Polyvinyl Alcohol-styrylpyridinium/beta-cyclodextrin Composite Nanofibers: Release Behavior and Potential Use for Wound Dressing [J]. Fibers and Polymers, 2016, 17(11): 1835-41.[27] ZHOU H, LI Z, NIU X, et al. The enhanced gas-sensing and photocatalytic performance of hollow and hollow core-shell SnO2-based nanofibers induced by the Kirkendall effect [J]. Ceramics International, 2016, 42(1): 1817-26.[28] ZHOU H, LI Z, NIU X, et al. The enhanced gas-sensing and photocatalytic performance of hollow and hollow core shell SnO2-based nanofibers induced by the Kirkendall effect (vol 42, pg 1817, 2016) [J]. Ceramics International, 2016, 42(6): 7897-.[29] ZHANG J, SONG M, WANG X, et al. Preparation of a cellulose acetate/organic montmorillonite composite porous ultrafine fiber membrane for enzyme immobilizatione [J]. Journal of Applied Polymer Science, 2016, 133(33):[30] ZHANG J, SONG M, LI D, et al. Preparation of Self-clustering Highly Oriented Nanofibers by NeedlelessElectrospinning Methods [J]. Fibers and Polymers, 2016, 17(9): 1414-20.[31] YUAN X, XU W, HUANG F, et al. Polyester fabric coated with Ag/ZnO composite film by magnetron sputtering [J]. Applied Surface Science, 2016, 390(863-9.[32] YUAN X, WEI Q, CHEN D, et al. Electrical and optical properties of polyester fabric coated with Ag/TiO2 composite films by magnetron sputtering [J]. Textile Research Journal, 2016, 86(8): 887-94.[33] YU J, ZHOU T, PANG Z, et al. Flame retardancy and conductive properties of polyester fabrics coated with polyaniline [J]. Textile Research Journal, 2016, 86(11): 1171-9.[34] YANG J, LI D, PANG Z, et al. Laccase Biosensor Based on Ag-Doped TiO2 Nanoparticles on CuCNFs for the Determination of Hydroquinone [J]. Nano, 2016, 11(12):[35] YANG J, LI D, FU J, et al. TiO2-CuCNFs based laccase biosensor for enhanced electrocatalysis in hydroquinone detection [J]. Journal of Electroanalytical Chemistry, 2016, 766(16-23.[36] WANG X, WANG Q, HUANG F, et al. The Morphology of Taylor Cone Influenced by Different Coaxial Composite Nozzle Structures [J]. Fibers and Polymers, 2016, 17(4): 624-9.[37] QIU Y, QIU L, CUI J, et al. Bacterial cellulose and bacterial cellulose-vaccarin membranes for wound healing [J]. Materials Science & Engineering C-Materials for Biological Applications, 2016, 59(303-9.[38] QIAO H, FEI Y, CHEN K, et al. Electrospun synthesis and electrochemical property of zinc ferrite nanofibers [J]. Ionics, 2016, 22(6): 967-74.[39] PANG Z, YANG Z, CHEN Y, et al. A room temperatureammonia gas sensor based on cellulose/TiO2/PANI composite nanofibers [J]. Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2016, 494(248-55.[40] NIE Q, PANG Z, LU H, et al. Ammonia gas sensors based on In2O3/PANI hetero-nanofibers operating at room temperature [J]. Beilstein Journal of Nanotechnology, 2016, 7(1312-21.[41] NARH C, LI G, WANG Q, et al. Sulfanilic acid inspired self-assembled fibrous materials [J]. Colloid and Polymer Science, 2016, 294(9): 1483-94.[42] LV P, XU W, LI D, et al. Metal-based bacterial cellulose of sandwich nanomaterials for anti-oxidation electromagnetic interference shielding [J]. Materials & Design, 2016, 112(374-82.[43] LV P, WEI A, WANG Y, et al. Copper nanoparticles-sputtered bacterial cellulose nanocomposites displaying enhanced electromagnetic shielding, thermal, conduction, and mechanical properties [J]. Cellulose, 2016, 23(5): 3117-27.[44] LV P, FENG Q, WANG Q, et al. Biosynthesis of Bacterial Cellulose/Carboxylic Multi-Walled Carbon Nanotubes for Enzymatic Biofuel Cell Application [J]. Materials, 2016, 9(3):[45] LV P, FENG Q, WANG Q, et al. Preparation of Bacterial Cellulose/Carbon Nanotube Nanocomposite for Biological Fuel Cell [J]. Fibers and Polymers, 2016, 17(11): 1858-65.[46] LUO L, XU W, XIA Z, et al. Electrospun ZnO-SnO2 composite nanofibers with enhanced electrochemical performance as lithium-ion anodes [J]. Ceramics International, 2016, 42(9): 10826-32.[47] LI W, LIU X, LIU C, et al. Preparation and Characterisation of High Count Yak Wool Yarns Spun by Complete Compacting Spinning and Fabrics Knitted from them [J]. Fibres & Textiles inEastern Europe, 2016, 24(1): 30-5.[48] LI G, WANG Q, LV P, et al. Bioremediation of Dyes Using Ultrafine Membrane Prepared from the Waste Culture of Ganoderma lucidum with in-situ Immobilization of Laccase [J]. Bioresources, 2016, 11(4): 9162-74.[49] LI G, SUN K, LI D, et al. Biosensor based on bacterial cellulose-Au nanoparticles electrode modified with laccase for hydroquinone detection [J]. Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2016, 509(408-14.[50] LI G, NANDGAONKAR A G, LU K, et al. Laccase immobilized on PAN/O-MMT composite nanofibers support for substrate bioremediation: a de novo adsorption and biocatalytic synergy [J]. Rsc Advances, 2016, 6(47): 41420-7.[51] LI D, ZANG J, ZHANG J, et al. Sol-Gel Synthesis of Carbon Xerogel-ZnO Composite for Detection of Catechol [J]. Materials, 2016, 9(4):[52] LI D, AO K, WANG Q, et al. Preparation of Pd/Bacterial Cellulose Hybrid Nanofibers for Dopamine Detection [J]. Molecules, 2016, 21(5):[53] KE H, PANG Z, PENG B, et al. Thermal energy storage and retrieval properties of form-stable phase change nanofibrous mats based on ternary fatty acid eutectics/polyacrylonitrile composite by magnetron sputtering of silver [J]. Journal of Thermal Analysis and Calorimetry, 2016, 123(2): 1293-307.[54] KE H, GHULAM M U H, LI Y, et al. Ag-coated polyurethane fibers membranes absorbed with quinary fatty acid eutectics solid-liquid phase change materials for storage and retrieval of thermal energy [J]. Renewable Energy, 2016, 99(1-9.[55] KE H, FELDMAN E, GUZMAN P, et al. Electrospun polystyrene nanofibrous membranes for direct contactmembrane distillation [J]. Journal of Membrane Science, 2016, 515(86-97.[56] HUANG F, LIU W, LI P, et al. Electrochemical Properties of LLTO/Fluoropolymer-Shell Cellulose-Core Fibrous Membrane for Separator of High Performance Lithium-Ion Battery [J]. Materials, 2016, 9(2):[57] ZONG X, CAI Y, SUN G, et al. Fabrication and characterization of electrospun SiO2 nanofibers absorbed with fatty acid eutectics for thermal energy storage/retrieval [J]. Solar Energy Materials and Solar Cells, 2015, 132(183-90.[58] ZHENG H, ZHANG J, DU B, et al. Effect of treatment pressure on structures and properties of PMIA fiber in supercritical carbon dioxide fluid [J]. Journal of Applied Polymer Science, 2015, 132(14):[59] ZHENG H, ZHANG J, DU B, et al. An Investigation for the Performance of Meta-aramid Fiber Blends Treated in Supercritical Carbon Dioxide Fluid [J]. Fibers and Polymers, 2015, 16(5): 1134-41.[60] XU C, HINKS D, SUN C, et al. Establishment of an activated peroxide system for low-temperature cotton bleaching using N- 4-(triethylammoniomethyl)benzoyl butyrolactam chloride [J]. Carbohydrate Polymers, 2015, 119(71-7.[61] WANG Q, NANDGAONKAR A, LUCIA L, et al. Enzymatic bio-fuel cells based on bacterial cellulose (BC)/MWCNT/laccase (Lac) and bacterial cellulose/MWCNT/glucose oxidase (GOD) electrodes [J]. Abstracts of Papers of the American Chemical Society, 2015, 249([62] WANG H, XU Y, WEI Q. Preparation of bamboo-hat-shaped deposition of a poly(ethylene terephthalate) fiber web by melt-electrospinning [J]. Textile Research Journal, 2015, 85(17):1838-48.[63] SIGDEL S, ELBOHY H, GONG J, et al. Dye-Sensitized Solar Cells Based on Porous Hollow Tin Oxide Nanofibers [J]. Ieee Transactions on Electron Devices, 2015, 62(6): 2027-32.[64] QIAO H, LUO L, CHEN K, et al. Electrospun synthesis and lithium storage properties of magnesium ferrite nanofibers [J]. Electrochimica Acta, 2015, 160(43-9.[65] QIAO H, CHEN K, LUO L, et al. Sonochemical synthesis and high lithium storage properties of Sn/CMK-3 nanocomposites [J]. Electrochimica Acta, 2015, 165(149-54.[66] NANDGAONKAR A, WANG Q, KRAUSE W, et al. Photocatalytic and biocatalytic degradation of dye solution using laccase and titanium dioxide loaded on bacterial cellulose [J]. Abstracts of Papers of the American Chemical Society, 2015, 249([67] LUO L, QIAO H, CHEN K, et al. Fabrication of electrospun ZnMn2O4 nanofibers as anode material for lithium-ion batteries [J]. Electrochimica Acta, 2015, 177(283-9.[68] LUO L, FEI Y, CHEN K, et al. Facile synthesis of one-dimensional zinc vanadate nanofibers for high lithium storage anode material [J]. Journal of Alloys and Compounds, 2015, 649(1019-24.[69] LUO L, CUI R, LIU K, et al. Electrospun preparation and lithium storage properties of NiFe2O4 nanofibers [J]. Ionics, 2015, 21(3): 687-94.[70] LI W, SU X, ZHANG Y, et al. Evaluation of the Correlation between the Structure and Quality of Compact Blend Yarns [J]. Fibres & Textiles in Eastern Europe, 2015, 23(6): 55-67.[71] LI D, LV P, ZHU J, et al. NiCu Alloy Nanoparticle-Loaded Carbon Nanofibers for Phenolic Biosensor Applications [J]. Sensors, 2015, 15(11): 29419-33.[72] LI D, LI G, LV P, et al. Preparation of a graphene-loaded carbon nanofiber composite with enhanced graphitization and conductivity for biosensing applications [J]. Rsc Advances, 2015, 5(39): 30602-9.[73] HUANG F, XU Y, PENG B, et al. Coaxial Electrospun Cellulose-Core Fluoropolymer-Shell Fibrous Membrane from Recycled Cigarette Filter as Separator for High Performance Lithium-Ion Battery [J]. Acs Sustainable Chemistry & Engineering, 2015, 3(5): 932-40.[74] GONG J, QIAO H, SIGDEL S, et al. Characteristics of SnO2 nanofiber/TiO2 nanoparticle composite for dye-sensitized solar cells [J]. Aip Advances, 2015, 5(6):[75] GAO D, WANG L, WANG C, et al. Electrospinning of Porous Carbon Nanocomposites for Supercapacitor [J]. Fibers and Polymers, 2015, 16(2): 421-5.[76] FU J, PANG Z, YANG J, et al. Hydrothermal Growth of Ag-Doped ZnO Nanoparticles on Electrospun Cellulose Nanofibrous Mats for Catechol Detection [J]. Electroanalysis, 2015, 27(6): 1490-7.[77] FU J, PANG Z, YANG J, et al. Fabrication of polyaniline/carboxymethyl cellulose/cellulose nanofibrous mats and their biosensing application [J]. Applied Surface Science, 2015, 349(35-42.[78] FU J, LI D, LI G, et al. Carboxymethyl cellulose assisted immobilization of silver nanoparticles onto cellulose nanofibers for the detection of catechol [J]. Journal of Electroanalytical Chemistry, 2015, 738(92-9.[79] DU B, ZHENG L-J, WEI Q. Screening and identification of Providencia rettgeri for brown alga degradation and anion sodium alginate/poly (vinyl alcohol)/tourmaline fiber preparation[J]. Journal of the T extile Institute, 2015, 106(7): 787-91.[80] CUI J, QIU L, QIU Y, et al. Co-electrospun nanofibers of PVA-SbQ and Zein for wound healing [J]. Journal of Applied Polymer Science, 2015, 132(39):[81] CHEN X, LI D, LI G, et al. Facile fabrication of gold nanoparticle on zein ultrafine fibers and their application for catechol biosensor [J]. Applied Surface Science, 2015, 328(444-52.[82] CAI Y, SUN G, LIU M, et al. Fabrication and characterization of capric lauric palmitic acid/electrospun SiO2 nanofibers composite as form-stable phase change material for thermal energy storage/retrieval [J]. Solar Energy, 2015, 118(87-95.[83] CAI Y, LIU M, SONG X, et al. A form-stable phase change material made with a cellulose acetate nanofibrous mat from bicomponent electrospinning and incorporated capric-myristic-stearic acid ternary eutectic mixture for thermal energy storage/retrieval [J]. Rsc Advances, 2015, 5(102): 84245-51.[84] ZHANG P, WANG Q, ZHANG J, et al. Preparation of Amidoxime-modified Polyacrylonitrile Nanofibers Immobilized with Laccase for Dye Degradation [J]. Fibers and Polymers, 2014, 15(1): 30-4.[85] XIA X, WANG X, ZHOU H, et al. The effects of electrospinning parameters on coaxial Sn/C nanofibers: Morphology and lithium storage performance [J]. Electrochimica Acta, 2014, 121(345-51.[86] WANG Q, NANDGAONKAR A G, CUI J, et al. Atom efficient thermal and photocuring combined treatments for the synthesis of novel eco-friendly grid-like zein nanofibres [J]. Rsc Advances, 2014, 4(106): 61573-9.[87] WANG Q, LI G, ZHANG J, et al. PAN Nanofibers Reinforced with MMT/GO Hybrid Nanofillers [J]. Journal of Nanomaterials, 2014,[88] WANG Q, CUI J, LI G, et al. Laccase Immobilized on a PAN/Adsorbents Composite Nanofibrous Membrane for Catechol Treatment by a Biocatalysis/Adsorption Process [J]. Molecules, 2014, 19(3): 3376-88.[89] WANG Q, CUI J, LI G, et al. Laccase Immobilization by Chelated Metal Ion Coordination Chemistry [J]. Polymers, 2014, 6(9): 2357-70.[90] PANG Z, FU J, LV P, et al. Effect of CSA Concentration on the Ammonia Sensing Properties of CSA-Doped PA6/PANI Composite Nanofibers [J]. Sensors, 2014, 14(11): 21453-65.[91] PANG Z, FU J, LUO L, et al. Fabrication of PA6/TiO2/PANI composite nanofibers by electrospinning-electrospraying for ammonia sensor [J]. Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2014, 461(113-8.[92] NANDGAONKAR A G, WANG Q, FU K, et al. A one-pot biosynthesis of reduced graphene oxide (RGO)/bacterial cellulose (BC) nanocomposites [J]. Green Chemistry, 2014, 16(6): 3195-201.[93] MENG L, WEI Q, LI Y, et al. Effects of plasma pre-treatment on surface properties of fabric sputtered with copper [J]. International Journal of Clothing Science and Technology, 2014, 26(1): 96-104.[94] LUO L, CUI R, QIAO H, et al. High lithium electroactivity of electrospun CuFe2O4 nanofibers as anode material for lithium-ion batteries [J]. Electrochimica Acta, 2014, 144(85-91.[95] LI X-J, WEI Q, WANG X. Preparation of magnetic polyimide/maghemite nanocomposite fibers by electrospinning[J]. High Performance Polymers, 2014, 26(7): 810-6.[96] LI X, WANG X, WANG Q, et al. Effects of Imidization Temperature on the Structure and Properties of Electrospun Polyimide Nanofibers [J]. Journal of Engineered Fibers and Fabrics, 2014, 9(4): 33-8.[97] LI D, YANG J, ZHOU J, et al. Direct electrochemistry of laccase and a hydroquinone biosensing application employing ZnO loaded carbon nanofibers [J]. Rsc Advances, 2014, 4(106): 61831-40.[98] LI D, PANG Z, CHEN X, et al. A catechol biosensor based on electrospun carbon nanofibers [J]. Beilstein Journal of Nanotechnology, 2014, 5(346-54.[99] LI D, LUO L, PANG Z, et al. Novel Phenolic Biosensor Based on a Magnetic Polydopamine-Laccase-Nickel Nanoparticle Loaded Carbon Nanofiber Composite [J]. Acs Applied Materials & Interfaces, 2014, 6(7): 5144-51.[100] LI D, LUO L, PANG Z, et al. Amperometric detection of hydrogen peroxide using a nanofibrous membrane sputtered with silver [J]. Rsc Advances, 2014, 4(8): 3857-63.[101] KE H, PANG Z, XU Y, et al. Graphene oxide improved thermal and mechanical properties of electrospun methyl stearate/polyacrylonitrile form-stable phase change composite nanofibers [J]. Journal of Thermal Analysis and Calorimetry, 2014, 117(1): 109-22.[102] KASAUDHAN R, ELBOHY H, SIGDEL S, et al. Incorporation of TiO2 Nanoparticles Into SnO2 Nanofibers for Higher Efficiency Dye-Sensitized Solar Cells [J]. Ieee Electron Device Letters, 2014, 35(5): 578-80.[103] HUANG X, MENG L, WEI Q, et al. Morphology and properties of nanoscale copper films deposited on polyestersubstrates [J]. International Journal of Clothing Science and Technology, 2014, 26(5): 367-76.[104] GAO D, WANG L, YU J, et al. Preparation and Characterization of Porous Carbon Based Nanocomposite for Supercapacitor [J]. Fibers and Polymers, 2014, 15(6): 1236-41.[105] FU J, QIAO H, LI D, et al. Laccase Biosensor Based on Electrospun Copper/Carbon Composite Nanofibers for Catechol Detection [J]. Sensors, 2014, 14(2): 3543-56.[106] FENG Q, ZHAO Y, WEI A, et al. Immobilization of Catalase on Electrospun PVA/PA6-Cu(II) Nanofibrous Membrane for the Development of Efficient and Reusable Enzyme Membrane Reactor [J]. Environmental Science & Technology, 2014, 48(17): 10390-7.[107] FENG Q, WEI Q, HOU D, et al. Preparation of Amidoxime Polyacrylonitrile Nanofibrous Membranes and Their Applications in Enzymatic Membrane Reactor [J]. Journal of Engineered Fibers and Fabrics, 2014, 9(2): 146-52.[108] DUAN F, ZHANG Q, WEI Q, et al. Control of Photocatalytic Property of Bismuth-Based Semiconductor Photocatalysts [J]. Progress in Chemistry, 2014, 26(1): 30-40.[109] CUI J, WANG Q, CHEN X, et al. A novel material of cross-linked styrylpyridinium salt intercalated montmorillonite for drug delivery [J]. Nanoscale Research Letters, 2014, 9([110] CAI Y, ZONG X, ZHANG J, et al. THE IMPROVEMENT OF THERMAL STABILITY AND CONDUCTIVITY VIA INCORPORATION OF CARBON NANOFIBERS INTO ELECTROSPUN ULTRAFINE COMPOSITE FIBERS OF LAURIC ACID/POLYAMIDE 6 PHASE CHANGE MATERIALS FOR THERMAL ENERGY STORAGE [J]. International Journal of Green Energy, 2014, 11(8): 861-75.[111] XIA X, LI S, WANG X, et al. Structures and properties ofSnO2 nanofibers derived from two different polymer intermediates [J]. Journal of Materials Science, 2013, 48(9): 3378-85.[112] WANG X, LI S, WANG H, et al. Progress in Research of Melt-electrospinning [J]. Polymer Bulletin, 2013, 7): 15-26.[113] WANG X, HE T, LI D, et al. Electromagnetic properties of hollow PAN/Fe3O4 composite nanofibres via coaxial electrospinning [J]. International Journal of Materials & Product Technology, 2013, 46(2-3): 95-105.[114] WANG Q, PENG L, LI G, et al. Activity of Laccase Immobilized on TiO2-Montmorillonite Complexes [J]. International Journal of Molecular Sciences, 2013, 14(6): 12520-32.[115] WANG Q, PENG L, DU Y, et al. Fabrication of hydrophilic nanoporous PMMA/O-MMT composite microfibrous membrane and its use in enzyme immobilization [J]. Journal of Porous Materials, 2013, 20(3): 457-64.[116] WANG Q, DU Y, FENG Q, et al. Nanostructures and Surface Nanomechanical Properties of Polyacrylonitrile/Graphene Oxide Composite Nanofibers by Electrospinning [J]. Journal of Applied Polymer Science, 2013, 128(2): 1152-7.[117] SHAO D, WEI Q, TAO L, et al. PREPARATION AND CHARACTERIZATION OF PET NONWOVEN COATED WITH ZnO-Ag BY ONE-POT HYDROTHERMAL TECHNIQUES [J]. Tekstil Ve Konfeksiyon, 2013, 23(4): 338-41.[118] QIAO H, YAO D, CAI Y, et al. One-pot synthesis and electrochemical property of MnO/C hybrid microspheres [J]. Ionics, 2013, 19(4): 595-600.[119] LIU H, CHEN D, WEI Q, et al. An investigation into thebust girth range of pressure comfort garment based on elastic sports vest [J]. Journal of the Textile Institute, 2013, 104(2): 223-30.[120] LI D, PANG Z, WANG Q, et al. Fabrication and Characterization of Polyamide6-room Temperature Ionic Liquid (PA6-RTIL) Composite Nanofibers by Electrospinning [J]. Fibers and Polymers, 2013, 14(10): 1614-9.[121] KUMAR D N T, WEI Q. Analysis of Quantum Dots for Nano-Bio applications as the Technological Platform of the Future [J]. Research Journal of Biotechnology, 2013, 8(5): 78-82.[122] KE H, LI D, ZHANG H, et al. Electrospun Form-stable Phase Change Composite Nanofibers Consisting of Capric Acid-based Binary Fatty Acid Eutectics and Polyethylene Terephthalate [J]. Fibers and Polymers, 2013, 14(1): 89-99.[123] KE H, LI D, WANG X, et al. Thermal and mechanical properties of nanofibers-based form-stable PCMs consisting of glycerol monostearate and polyethylene terephthalate [J]. Journal of Thermal Analysis and Calorimetry, 2013, 114(1): 101-11.[124] KE H, CAI Y, WEI Q, et al. Electrospun ultrafine composite fibers of binary fatty acid eutectics and polyethylene terephthalate as innovative form-stable phase change materials for storage and retrieval of thermal energy [J]. International Journal of Energy Research, 2013, 37(6): 657-64.[125] HUANG F, ZHANG H, WEI Q, et al. Preparation and characterization of PVDF nanofibrous membrane containing bimetals for synergistic dechlorination of trichloromethane [J]. Abstracts of Papers of the American Chemical Society, 2013, 246( [126] HUANG F, XU Y, LIAO S, et al. Preparation of Amidoxime Polyacrylonitrile Chelating Nanofibers and Their Application forAdsorption of Metal Ions [J]. Materials, 2013, 6(3): 969-80.[127] GAO D, WANG L, XIA X, et al. Preparation and Characterization of porous Carbon/Nickel Nanofibers for Supercapacitor [J]. Journal of Engineered Fibers and Fabrics, 2013, 8(4): 108-13.[128] FENG Q, WANG Q, TANG B, et al. Immobilization of catalases on amidoxime polyacrylonitrile nanofibrous membranes [J]. Polymer International, 2013, 62(2): 251-6.[129] CAI Y, ZONG X, ZHANG J, et al. Electrospun nanofibrous mats absorbed with fatty acid eutectics as an innovative type of form-stable phase change materials for storage and retrieval of thermal energy [J]. Solar Energy Materials and Solar Cells, 2013, 109(160-8.[130] CAI Y, ZONG X, BAN H, et al. Fabrication, Structural Morphology and Thermal Energy Storage/Retrieval of Ultrafine Phase Change Fibres Consisting of Polyethylene Glycol and Polyamide 6 by Electrospinning [J]. Polymers & Polymer Composites, 2013, 21(8): 525-32.[131] CAI Y, GAO C, ZHANG T, et al. Influences of expanded graphite on structural morphology and thermal performance of composite phase change materials consisting of fatty acid eutectics and electrospun PA6 nanofibrous mats [J]. Renewable Energy, 2013, 57(163-70.[1]张权,董建成,陈亚君,王清清,魏取福.水热反应温度对PMMA/TiO_2复合纳米纤维膜的形貌和性能的影响[J].材料科学与工程学报,2017,(05):785-789.[2]周建波,卢杭诣,张权,代雅轩,王清清,魏取福.醋纤基载药纳米纤维膜制备及药物缓释行为研究[J].化工新型材料,2017,45(10):223-225.[3]盛澄成,徐阳,魏取福,乔辉.Cu/Al_2O_3复合薄膜的制备及其抗氧化性能[J].材料科学与工程学报,2017,35(04):596-599+606.[4]张金宁,何慢,陈昀,曹建华,杨占平,宋明玉,魏取福.二醋酸纤维/OMMT复合增强纳米纤维膜及其过滤性能研究[J].化工新型材料,2017,45(08):84-86.[5]周建波,卢杭诣,张权,王清清,魏取福.CA/β-CD复合纳米纤维的制备与表征研究[J].化工新型材料,2017,45(07):244-246.[6]敖克龙,李大伟,吕鹏飞,王清清,魏取福.载钯细菌纤维素纳米纤维的制备及表征[J].化工新型材料,2017,45(07):214-216.[7]盛澄成,徐阳,魏取福,乔辉.双面结构电磁屏蔽材料的制备及抗氧化性能研究[J].化工新型材料,2017,45(07):57-59.[8]刘文婷,宁景霞,李沛赢,魏取福,黄锋林.PVDF-HFP/LLTO复合锂离子电池隔膜的电化学性能研究[J].化工新型材料,2017,45(07):50-53.[9]邱玉宇,蔡维维,邱丽颖,王清清,魏取福.负载王不留行黄酮苷纳米纤维作为创伤敷料的研究[J].生物医学工程学杂志,2017,34(03):394-400.[10]俞俭,李祥涛,高大伟,刘丽,魏取福,林洪芹.木棉/棉混纺机织物的服用性能[J].丝绸,2017,54(06):22-26.[11]盛澄成,徐阳,魏取福.层状复合电磁屏蔽材料的制备及性能研究[J].化工新型材料,2017,45(05):61-63.[12]张权,董建成,马梦琴,王清清,魏取福.柔性PMMA/TiO_2复合超细纤维的制备及表征[J].化工新型材料,2017,45(05):90-92.[13]张金宁,宋明玉,王小宇,陈昀,曹建华,杨占平,魏取福.多孔二醋酸超细纤维膜的固定化酶及染料降解性能[J].化工新型材料,2017,45(05):173-175.[14]高大伟,王春霞,林洪芹,魏取福,李伟伟,陆逸群,姜宇.二氧化钛纳米管的制备及其光催化性能[J].纺织学报,2017,38(04):22-26.[15]柯惠珍,李永贵,王建刚,袁小红,陈东生,魏取福.磁控溅射法提高定型相变材料的储热和放热速率[J].功能材料,2017,48(03):3163-3167.[16]张权,代雅轩,马梦琴,王清清,魏取福.光敏抗菌型静电纺丙烯酸甲酯/丙烯酸纳米纤维的制备及其性能表征[J].纺织学报,2017,38(03):18-22.。

甘草次酸修饰多西紫杉醇磁性纳米粒的制备与表征作者：王莎莎陈家琦王华华黄胜楠贾永艳祝侠丽来源：《中国药房》2020年第19期摘要目的：制备甘草次酸修饰多西紫杉醇磁性纳米粒（GA-DTX-NGO/IONP-NPs），并对其理化性质进行评价。

方法：以磁性纳米氧化石墨烯（NGO/IONP）作为抗肿瘤药物载体，多西紫杉醇（DTX）为模型药物，甘草次酸（GA）為靶头分子。

采用水热法合成NGO/IONP、酰胺化反应合成GA修饰的壳聚糖（GA-CS）后，采用傅里叶红外光谱法、差示扫描量热法及振动样品磁测量法等对两者进行表征。

采用离子凝胶化法制备GA-DTX-NGO/IONP-NPs;采用透射电镜、纳米粒度分析仪等对其微观形态、粒径及Zeta电位进行观察和测定;采用超滤离心法测定其包封率和载药量;通过观察有无外加磁场时的状态考察其磁性;结合808 nm激光对其进行光热转换试验。

结果：成功合成了NGO/IONP和GA-CS，且NGO/IONP呈现超顺磁性。

GA-DTX-NGO/IONP-NPs在透射电镜下呈圆球状，粒径为（262.8±4.23） nm，Zeta电位为（13.6±1.51） mV，包封率为（94.29±0.50）%，载药量为（17.12±0.12）%。

GA-DTX-NGO/IONP-NPs的外观呈黑色，分散均匀;其在外加磁场下磁性纳米粒可定向移动，显示出良好的磁定向性。

在808 nm激光照射下，GA-DTX-NGO/IONP-NPs 具有良好的光热转换效应，且呈浓度和时间依赖趋势。

结论：本研究成功制备了一种磁性纳米载药系统GA-DTX-NGO/IONP-NPs，可为肿瘤的磁热-化疗联合治疗提供一定的理论依据。

关键词磁性纳米氧化石墨烯;甘草次酸;多西紫杉醇;磁性纳米粒ABSTRACT OBJECTIVE： To prepare Glycyrrhetinic acid-modified docetaxel magnetic nanoparticles （GA-DTX-NGO/IONP- NPs）， and to evaluate its physicochemical properties. METHODS： Magnetic nano graphene oxide （NGO/IONP） was chosen as the anti-tumor drug carrier， docetaxel （DTX） as the model drug and glycyrrhetinic acid （GA） as the target molecule. Firstly， NGO/IONP was synthesized by hydrothermal method and GA-CS was synthesized by amidation reaction. Fourier IR spectrometer， DSC and vibration sample magnetic measuring instrument were used to characterize NGO/IONP and GA-CS. GA-DTX-NGO/IONP-NPs were prepared by the ion gelation method. TEM and particle size analyzer were used to observe and determine the morphology， particle size and Zeta potential of GA-DTX-NGO/IONP-NPs; the ultrafiltration-centrifugation method was used to determine encapsulation efficiency and drug loading amount; the magnetic properties were investigated by investigating the state with or without external magnetic field; the photothermal conversion test was carried out with laser irradiation of 808 nm. RESULTS： NGO/IONP and GA-CS were successfully synthesized， and NGO/IONP exhibited superparamagnetism characteristics. GA-DTX-NGO/IONP-NPs were spherical under TEM， the particle size was （262.8±4.23） nm and the Zeta potential was （13.6±1.51） mV. The encapsulation rate and drug loading amount were （94.29±0.50）% and （17.12±0.12）%，respectively. GA-DTX-NGO/IONP-NPs were black in appearance and evenly dispersed. Under the external magnetic field， the magnetic nanoparticles could move directionally， showing good magnetic properties. GA-DTX-NGO/IONP-NPs showed a good concentration- and time-dependent photothermal conversion effect under 808 nm laser irradiation. CONCLUSIONS： GA-DTX-NGO/IONP-NPs are successfully prepared. This study could provide some theoretical basis for the combined treatment of magnetic heating-chemotherapy for liver tumors.KEYWORDS Magnetic nano graphene oxide; Glycyrrhetinic acid; Docetaxel; Magnetic nanoparticles肝癌是危害人类健康的重大疾病之一 [1-2]。

“Graphene”研究及翻译摘要：查阅近5年我国SCI、EI期源刊有关石墨烯研究873篇，石墨烯研究的有关翻译存在很大差异。

从石墨烯的发现史及简介，谈石墨烯内涵及研究的相关翻译。

指出“石墨烯”有关术语翻译、英文题目、摘要撰写应注意的问题。

关键词：石墨烯；石墨烯术语；翻译石墨烯是目前发现的唯一存在的二维自由态原子晶体，它是构筑零维富勒烯、一维碳纳米管、三维体相石墨等sp2杂化碳的基本结构单元，具有很多奇异的电子及机械性能。

因而吸引了化学、材料等其他领域科学家的高度关注。

近5年我国SCI、EI期源刊研究论文873篇，论文质量良莠不齐，发表的论文有35.97%尚未被引用过，占国际论文被引的4.84%左右。

石墨烯研究的有关翻译也存在很大差异。

为了更好的进行国际学术交流，规范化专业术语。

本文就“graphene”的内涵及翻译谈以下看法。

l “Graphene”的发现史及简介1962年，Boehm等人在电镜上观察到了数层甚至单层石墨（氧化物）的存在，1975年van Bom-mel等人报道少层石墨片的外延生长研究，1999年德克萨斯大学奥斯汀分校的R Ruoff等人对用透明胶带从块体石墨剥离薄层石墨片的尝试进行相关报道。

2004年曼彻斯特大学的Novoselov和Geim小组以石墨为原料，通过微机械力剥离法得到一系列叫作二维原子晶体的新材料——石墨烯，并于10月22日在Sclence期刊上发表有关少层乃至单层石墨片的独特电学性质的文章，2010年Gelm和No-voselov获得了诺贝尔物理学奖。

石墨烯有着巨大的比表面积（2630 m2/g）、极高的杨氏模量（1.06 TPa）和断裂应力（～130GPa）、超高电导率（～106 S/cm）和热导率（5000W/m·K）。

石墨烯中的载流子迁移率远高于传统的硅材料，室温下载流子的本征迁移率高达200000 cm2/V.s），而典型的硅场效应晶体管的电子迁移率仅约1000 cm2/V.s。

固体脂质纳米粒及其脑靶向作用的研究进展李海珍;胡彦武;姚慧敏【摘要】固体脂质纳米粒(SLN)是近年新兴起的一种亚微粒给药系统,其具有稳定性高、生物相容性高、靶向性好、可用于大规模生产等优点,引起相关研究者的高度关注.本文查阅中外文献,对SLN的制备技术方法、理化性质的测定及其脑靶向作用进行总结归纳,为SLN的进一步研究应用提供一定的参考依据.【期刊名称】《通化师范学院学报》【年(卷),期】2018(039)008【总页数】7页(P43-49)【关键词】固体脂质纳米粒;制备方法;理化性质;脑靶向【作者】李海珍;胡彦武;姚慧敏【作者单位】通化师范学院吉林省长白山药用植物研究重点实验室吉林通化134002;长春中医药大学药学院;通化师范学院吉林省长白山药用植物研究重点实验室吉林通化134002;通化师范学院吉林通化134002【正文语种】中文【中图分类】R96固体脂质纳米粒（Solid Lipid Nanoparticle，SLN）的概念是在1991年由Müller首次提出，以固态的天然或合成的高熔点类脂作为载药材料，使药物包裹于脂质中或分散在纳米粒表面形成粒径约为50～1000nm的固态胶体的新型药物传递载体，可替代脂质体、微乳、聚合物胶束等传统药物递送系统［1］.SLN结合了其他几个新型载体系统的优点，既有聚合物纳米粒的高生物相容性和物理稳定性，避免药物氧化、降解或泄漏以及可控制药物释放及良好的靶向性［2］，又兼有脂质体、乳剂的低毒性、操作简单，可用于大规模生产的优点［2-4］.此外，由于SLN的药物是包裹在脂质材料内部，因此解决了药物水溶性差的问题，同时可延长药物的半衰期，从而克服了其他载体系统存在的生物利用度低等问题［4］.本文就近年来国内外固体脂质纳米粒的制备方法与技术，理化性质的测定及临床应用，尤其是作用于脑靶向的应用进行综述.1 固体脂质纳米粒的制备技术与方法1.1 辅料SLN是由脂质材料、乳化剂、水及有机溶剂组成.SLN能否形成取决于脂质材料的类型，通常使用的天然或合成材料作为骨架脂质，常用脂质的材料包括三酰甘油酯（三月桂酸甘油酯、三硬脂酸甘油酯等）、部分甘油酯（山嵛酸甘油酯、肉豆蔻甘油酯等）、脂肪酸（硬脂酸、软脂酸）、类固醇激素（胆固醇）和蜡（棕榈酸鲸蜡酯）等具有有生物相容性，体内降解、低毒性的脂质材料［5］.此外，一些研究表明，加入一定比例的液态脂质，如油酸、中链甘油三油脂等，可提高药物的包封率及载药量.因此，实验中应根据药物性质及制备方法等处方设计因素选择合适的脂质材料.表面活性剂的类型和用量与SLN的粒径、包封率等性质密切相关.不同的制备方法或阶段表面活性剂有乳化剂和稳定剂作用，作为乳化剂可降低溶液的表面张力；作为稳定剂使纳米粒稳定分散，稳定SLN.此外,乳化剂的混合使用能有效防止颗粒团聚［6-7］，因此在制备过程中常使用两种或两种以上混合表面活性剂.常用的表面活性剂有胆酸盐类（去氢胆酸钠、胆酸钠等）、磷脂类（大豆卵磷脂、蛋黄磷脂等）、短链醇类（丁酸、丁醇等）以及非离子表面活性剂（如泊洛沙姆系列、聚山梨酯系列等）［8-9］.1.2 SLN制备方法1.2.1 乳化蒸发-低温固化法将适量的药物和载药脂质溶于适当的有机溶剂（75～80℃）中形成有机相，另取表面活性剂溶于纯水中作为水相（75～80℃），在恒温条件下（75～80℃）将有机相加入水相中高速搅拌乳化并除去有机溶剂，冰水浴固化一段时间后，经0.45微孔滤膜过滤即得SLN［10］.与其他制备方法相比较，此方法具有设备简单易得，成本较低，所得SLN混悬液分散均匀，适合实验室研究使用等特点.Yadav A等［10］制备的白藜芦醇SLNs（R-SLNs）的粒径为286nm，药物包封率为91.25%，具有缓释作用，脑内白藜芦醇（RSV）含量为游离RSV时的4.5倍.神经行为学分析表明，R-SLNs成功地改善了bccao大鼠的认知功能，有希望作为治疗与年龄相关的神经退行性疾病的一种新治疗策略.张洪等［11］采用乳化蒸发-低温固化法成功制备了稳定的索拉非尼SLN，所制得的SLN呈类球形，平均粒径为（108.2±7.0）nm，分布均匀，平均包封率为（73.49±1.87）%，体外试验结果表明其具有缓释作用.Xiaolie He等［12］采用乳化低温凝固法合成了姜黄素和右旋氨基丁醇固体脂质纳米粒（Cur-DL-SLNs），并采用MTT法、流式细胞仪检测细胞摄取等方法研究了纳米粒在皮质酮诱导的大抑郁模型中的抗抑郁活性，结果表明,Cur-DL-SLNs可能成为治疗重度抑郁症的有效手段.1.2.2 微乳法首先将药物与脂质材料水浴加热熔融后加入乳化剂、助乳化剂和纯水制备透明或半透明O/W或W/O型微乳，然后将微乳快速分散于0～2℃纯水中即得SLN.该法的缺点是乳化剂用量大，不易除去，且载药量较低；此外，由于微乳是热力学稳定体系，当温度发生改变时纳米粒可恢复成微乳［13］.优点是设备简单容易操作，基本无需使用三氯甲烷等有毒有机溶剂，有利于大规模生产的实现.李楠等［14］采用微乳法，根据伪三元相图法考察筛选微乳中油相、乳化剂、助乳化剂三相因素，确定最佳微乳处方；以包封率和载药量为指标，采用正交试验进行最终SLN处方优化，所得姜黄素SLN粒径较小，包封率及载药量较好.Elham sadati Behbahani等［15］以硬脂酸和三棕榈酸甘油酯为固体脂质，Tween 80和Span 80为表面活性剂，通过微乳液和超声法制备了姜黄素SLNS（Cur-SLNs），在中心复合设计基础上采用响应面法对考察SLNS的平均直径和包封效率关系.结果表明，Cur-SLNs呈球形，平均直径21nm，粒径和包封率分别为112.0±2.6nm和98.7±0.3%，且具有缓释效果.朴林梅［16］考察不同方法制备月见草油SLN，与其他方法相比较，微乳法制备的SLN包封率高且粒径较小，可确定为制备方法.同时进行SLN质量评价和药效学评价，实验表明月见草油SLN稳定性良好，可用于治疗急性高脂血症.1.2.3 薄膜-超声法将药物和载药脂质溶于有机溶剂中旋转蒸发，形成均匀薄膜，与含表面活性剂的水相混合，冰水浴条件下超声后得SLN.此方法操作简便，但不易成膜且成膜不均匀，所制备的SLN粒径分布较广，易产生金属污染.该方法适合小分子成份如黄酮类、倍半萜类等药物制备.罗小燕［17］等人使用薄膜-超声法以包封率为指标，采用正交设计优化法优化处方，所制备的芦丁SLN具有缓释效果.严春临等［18］以薄膜-超声法吴茱萸次碱SLN（Rut-SLN），采用星点设计对处方的药脂比、初乳化剂与脂质质量比、乳化剂质量三个因素进行优化，以粒径、包封率和Zeta电位为评价指标，采用效应面法选取最佳处方，所得Rut-SLN性质稳定、包封率高.侯军［19］以硬脂酸为脂质，卵磷脂为载体，采用旋转薄膜蒸发法制备盐酸小檗碱SLN（BH-SLN），以包封率为指标，采用正交试验筛选处方，结果表明，药脂比、硬脂酸和卵磷脂质量比、Tween-80浓度是影响包封率和载药量的主要因素，体外释放试验也表明BH-SLN具有缓释效应.1.2.4 高压匀质法将药物和载药脂质加热熔融，边搅拌边加入含表面活性剂的水溶液中制成初乳，经高压匀质机均质数次，冷却至室温即可形成SLN混悬液.高压均质法是目前工业化大规模生产纳米粒的主要方法，制得SLN粒径较小；同时又存在对设备的要求较高，制得纳米粒相对不稳定，易受温度影响而析出脂质等问题.周华峰等［20］采用高压均质法制备咪喹莫特SLN透皮吸收制剂，其优化条件下制备的药物SLN对皮肤无刺激性，有较好的体外释放性能及皮肤贮存能力，有望作为咪喹莫特透皮给药新制剂.Rompicharla SVK等［21］采用高压匀质法，以胆固醇为脂质，以泊洛沙姆-188为稳定剂制备姜黄素SLN（cur-SLN），采用质量优化设计法进行处方优化.优化的SLN粒径较小、分布较窄，包封率为76.9±1.9%，并通过DSC、FTIR、XRD和药物释放对SLN进行了进一步表征；体外细胞实验表明，与游离姜黄素相比，cur-SLN具有更好的细胞毒性和摄取性，而且SLN诱导的细胞凋亡明显增加，为该制剂在临床上用于癌症治疗提供了可能.Elisabett等［22］研究结果表明，高压均质法生产的黄体酮SLN（PRG-SLN）有良好的物理和化学稳定性，均质均匀，在生产后6个月内无团聚现象，对PRG具有较高的包封率，能有效控制PRG的释放和皮肤吸收率.1.2.5 超声分散法取药物与载药脂质加热熔融后作为油相，将含表面活性剂的水溶液趁热加入油相中搅拌后，用带探头的超声分散仪在一定温度下超声分散，将分散后的液体在搅拌下迅速加入分散相（0～2℃）中，搅拌固化后得SLN.该方法工艺简单易于操作，制得纳米粒粒径较小，且不用使用有机溶剂，但其制得的混悬液浓度较低.吕佳等［23］使用超声分散法制备了苦参碱SLN用于肝纤维化的治疗，采用正交试验优选处方工艺，制备的SLN性质稳定，粒径较小且分布均匀.Mara Ferreira等［24］以十六烷基棕榈酸酯为基质将水溶性差的药物甲氨蝶呤（MTX）包裹于SLN中，并采用依那西普（etanercep）与SLNS结合的联合治疗方法.脂质纳米粒直径从292nm到356nm，与人角质细胞和成纤维细胞具有生物相容性.体外研究表明，MTX在生理和皮肤模拟环境下具有较好的缓释特性.猪耳皮肤渗透试验表明，MTX-SLNS和MTX-etanercep-SLNS可显著提高MTX的生物利用度.Kamel M Kamel等［25］用70%乙醇提取肉桂和牛至的活性成分，采用超声分散法制备肉桂和牛至提取物SLN，并采用壳聚糖包裹形成核/壳纳米颗粒，且物理化学性质稳定.实验结果证实，这两种提取物对结肠癌具有细胞毒活性，此外，其与5-氟尿嘧啶可降低毒副作用.2 药物固体脂质纳米粒的理化性质及表征2.1 外观形态检测一般采用负染法进行检测，取稀释的SLN于铜网上，加2%的磷钨酸染色后使用透射电镜观察其外形及粒径，一般以完整、分布均匀的球形或类球形为最好.2.2 粒径及Zeta电位检测SLN的外观形态、粒径及Zeta电位检测是其处方优化时考察的重要指标.粒径及Zeta电位检测最常用的检测仪器是激光粒度测定仪及激光电位粒径分析仪，可以同时对二者进行检测，也有单独使用光子相关光谱、电位分析仪等仪器检测电位，使用粒径检测仪等检测粒径.SLN的粒径应在50～1000nm的且呈正态分布，Zeta电位一般控制在-20～-45mV.Zeta电位是指粒子表面与中性溶液之间的电位差，根据扩散双电层原理，纳米粒分散体系的稳定性主要取决于Zeta电位的大小，粒子表面电荷量直接影响粒子间斥力势能和溶剂化作用的大小，进而影响非均相体系的稳定性［26］.Zeta电位（绝对值）高的粒子间的电荷排斥作用大，因而不容易发生聚集，使整个体系处于相对平衡的状态.2.3 包封率与载药量包封率（Entrapment efficiency，EE）与载药量（Loading efficiency，LE）的检测需先测定药物总量W总和未包进纳米粒的药物的量W游离，然后按照下列公式［27］计算SLN的包封率及载药量.式中W载体是纳米粒中载体的质量.药物总量测定是使用有机溶剂（甲醇、无水乙醇等）或物理方法（如高速离心）将纳米乳破乳后测定的药物的含量即为W总测，将SLN与游离药物分离后测定溶液中药物的含量为W游离.文献报道［28］，分离SLN与游离药物的方法主要有超速离心法、葡聚糖凝胶层析柱法、超滤离心法、透析法等.葡聚糖凝胶层析柱法是利用分子筛的原理，将未进入凝胶孔内的大分子物质先洗脱下来，进入凝胶孔的小分子药物被洗脱下来，从而分离纳米粒和游离药物.此方法重现性好、快速有效、但成本较高［29］.超速离心法是将SLN溶液加入超速离心管中，利用离心力将纳米粒与游离药物分离，方法简单快速［30］.超滤法是将SLN加入适当截留分子量的超滤离心管中，离心将固体脂质纳米粒与游离药物分离，此方法在常温下进行，设备简单无相变，易于操作［31］.透析法是利用小分子物质可通半透膜而大分子则无法通过的性质，把药物放入置于透析介质中的透析袋中，游离药物可透过透析袋渗出到透析袋外，而纳米粒则因较大粒径而截留在透析袋内而达到分离效果［32］.SLN的载药量及包封率与药物的溶解性有关.脂溶性药物在水中溶解性差，易与载药脂质相结合，其纳米粒在水中分散量较小，包封率高；水溶性药物则相反，不易与脂质结合，包封率较低［33］.2.4 体外释放度SLN通常有3种包封结构模型：（1）固溶体模型，药物以分子形态分散于脂质材料中；（2）核-壳模型，药物聚集于外壳，表现为突释行为；（3）核-壳模型，药物浓集于内核，表现为缓释行为.因此，考察体外释放度可以初步判定药物包裹模型.其方法是将药物脂质置于透析袋中，在与释药部位相似生理环境的溶液中进行体外释放度的测定.2.5 结晶度和多晶型分析脂质纳米粒的结晶度和晶型可以反映脂质与药物相互作用的程度，是考察SLN性能的重要指标之一.示差扫描量热分析（Differential scan⁃ningcalorimetry，DSC）是测量输入到试样和参比物的热流量差或功率差与温度或时间的关系，可检测结晶相变的的特征；X-射线衍射（X-ray dif⁃fractometry，XRD）是利用晶体形成的X射线衍射，对物质进行内部原子在空间分布状况的结构分析方法，可检测药物晶型，这两种技术广泛用于药物晶型的检测.Rompicharla SVK等［21］采用DSC和XRD对cur-SLN进行表征，二者结果均显示游离姜黄素具有结晶性质，而cur-SLN则丧失了结晶性质，表明药物处于熔融状态，包裹于脂质中.Kuldeep Rajpoot等［22］对奥沙利柏 SLN（op-SLN）进行表征，其中XRD谱图中奥沙利铂药物具有特征衍射峰，而op-SLN XRD谱中特征峰消失，表明奥沙利铂的以非晶形状态分散于SLN中；DSC研究中奥利沙铂在259.7℃有一熔融峰，在奥沙利铂op-SLN图中则无此熔融峰，表明药物此时处于非晶形状态，结果与XRD相吻合.3 SLN作用于脑靶向的研究3.1 脑靶向作用的限制中枢神经系统疾病如脑梗死、脑肿瘤、偏头痛、血管性痴呆等发病率在逐年持续增高，但由于血脑屏障阻碍药物作用于治疗部位，目前上市药物无法发挥预期作用.血脑屏障（brainbloodbar⁃rier，BBB）存在于中枢神经系统（Central Nervous System，CNS）与血液间，是维持脑部自身的微环境动态平衡的生理屏障，由脑毛细血管内皮细胞、完整结构基膜和神经胶质膜3层结构构成，属于神经血管单元［35］，它不仅有供给脑组织营养的作用，也可通过调节外周血液与CNS之间物质交换，限制血液中的有害物质进入脑组织，保证脑内环境的相对稳定，对大脑形成保护作用.然而其独特结构也是药物作用于脑组织的最大屏障，几乎阻碍了所有大分子药物（如基因片段、酶类等）及98%的小分子药物透过BBB到达CNS.故而多数药物无法到达作用靶点或作用靶点的药物浓度低于最低有效治疗浓度而不能发挥药效，从而限制了很多药物应用于CNS疾病［36］.除此之外，外排蛋白如P-糖蛋白（P-gp）的作用也成为脂溶性的小分子药物进入脑组织的障碍.3.2 脑靶向制剂的研究目前，能够绕过BBB直接进入到CNS的给药方式及提高药物透过血脑屏障量的脑靶向制剂已经成为治疗CNS相关疾病的有效手段.理想的脑靶向制剂应具备趋脑性和透过BBB有效性［37］.根据BBB的独特结构和转运性质，目前常用的促进药物通过BBB的方法包括制备前体药物、血脑屏障的可逆开放法，即添加适量渗透促进剂使有效物质能够穿过BBB作用于脑部、改变给药途径如脑植入或运用载体系统如聚合物纳米粒、固体脂质纳米粒等实现脑靶向给药［38］.此外，有研究证实，鼻粘膜给药可使药物避开BBB直接作用于大脑，张文静［39］制备的富马酸喹硫平SLN原位凝胶（QF-SLN-gel）通过鼻腔给药，不仅可以避开BBB直接进入大脑，避免首过效应，而且鼻粘膜的黏附量增加，提高其在脑内含药量，而达到靶向作用.3.3 SLN作用于脑靶向研究SLN作为载药入脑的新型给药系统受到国内外高度关注.但对其透过BBB机制研究不甚明确，可能的机制有：（1）SLN粒径较小，可以直接穿过血脑屏障而发挥药效；（2）免疫吞噬细胞转运，大脑处于免疫系统的监控下，免疫细胞如中性粒细胞、巨噬细胞等可以选择性地跨过BBB到达 CNS［40］.因此，载药 SLN 可被免疫细胞吞噬后释放并扩散入脑.Afergan E［41］实验表明，完整的脂质体可通过被单核细胞吞噬而透过BBB进入大鼠和兔的脑组织.（3）与脑血管内皮细胞发生膜融合［42］，BBB结构与内皮组织紧密相连，有研究表明［43］带有负电荷的SLN可通过内皮细胞的连接处直接进入脑部.（4）减少P-gp的外排作用，研究表明［44］，SLN包裹能有效躲避P-gp的外排作用，增加药物在大脑内皮细胞中的积聚.（5）表面活性剂作用，SLN含表面活性剂，可提高细胞膜对脂质的溶解度，从而增加血管内皮细胞膜的流动性，提高了BBB对药物的通透性；此外网状内皮系统具有吞噬作用，能将SLN从血液中除去，通过对纳米粒的结构修饰，可延长纳米粒体内循环时间，并避开网状内皮系统的清除作用［45］.4 结论与展望固体脂质纳米粒（SLN）作为一种新型药物递送系统具有许多优点，它可以解决许多用药限制的难题，在化学药品、生物制品及中药制剂领域广泛应用.同时，SLN也存在一些如载药量低，易泄露等问题，需要对SLN进行进一步研究，对脂质材料进行修饰或开发新的载体来克服这些问题.随着这些问题的解决，SLN可实现规模化生产，广泛地应用于临床治疗中.参考文献：【相关文献】［1］Schwarz C，Mehnert W，Lucks JS，et al.Solid lipid nanoparticles（SLN）for controlled drug delivery.I.Produc⁃tion，characterization and sterilization［J］.Control Release，1994，30：83-96.［2］耿叶慧，杨丽，张瑜，等.吡喹酮固体脂质纳米粒的制备及其理化性质研究［J］.中国药房，2007，18（28）：2197-2199.［3］曹露晔，闫晶超，王玉生，等.蓝萼甲素固体脂质纳米粒的制备及理化性质研究［J］.中国药房，2008，9（9）：666-668.［4］Jenning V，Gohla SH.Encapsulation of retinoids in solid lipid nanoparticles（SLN）［J］.Microencapsul，2001，18：149-158.［5］Mukherjee S，Ray S，Thakur RS.Solid lipid nanoparticles：a modern formulation approach in drug deliv⁃ery system［J］.Indian Journal of Pharmaceutical Sciences，2009，71（4）：349-358.［6］Cavalli R，Caputo O，Gasco MR.Solid lipospheres of doxorubicin and idarubicin ［J］.International Journal of Pharmaceutics，1993，89（1）：R9-R12.［7］刘德育，罗德凤，叶建涛.人参皂苷Rd固体脂质纳米粒的制备［J］.中国医院药学杂志，2010，30（1）：25-30.［8］邹瑜.多西他赛固体脂质纳米粒的研究［D］.沈阳：沈阳药科大学，2007.［9］李园.石杉碱甲固体脂质纳米粒的研究［D］.广东：广东药学院，2010.［10］Yadav A，Sunkaria A，Singhal N，et al.Resveratrol loaded solid lipid nanoparticles attenuate mitochondrial oxi⁃dative stress in vascular dementia by activating Nrf2/HO1 pathway［J］.NeurochemistryInternational，2018，112：239-254.［11］张洪，张福明，闫士君.索拉非尼固体脂质纳米粒冻干粉制备及体外释药特性研究［J］.中国药学杂志，2013，48（3）：196-202.［12］Xiaolie He，Li Yang，Mei Wang，et al.Targeting the Endocannabinoid/CB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparti⁃cles［J］.Cellular Physiologyand Biochemistry，2017，42：2281-2294.［13］王金玲，孙进，何仲贵.微乳及其在药学中应用［J］.中国药剂学杂志，2009，7（4）：356-364.［14］李楠，李锡晶，王倩.微乳法制备姜黄素固体脂质纳米粒［J］.中国药房，2015，26（19）：2698-2701.［15］Elham sadati Behbahani，Mehrorang Ghaedi，Mo⁃hammadreza Abbaspour，et al.Optimization and characteriza⁃tion of ultrasound assisted preparation of Curcumin-loaded solid lipid nanoparticles：Application of central composite design，thermal analysis and X-ray diffraction techniques［J］.Ultrasonics Sonochemistry，2017，38：271-280.［16］朴林梅.月见草油固体脂质纳米粒的研制［D］.延吉：延边大学，2015.［17］罗小燕，吕竹芬，燕忠，等.薄膜-超声法制备芦丁固体脂质纳米粒的研究［J］.西北药学杂志，2015，30（3）：267-270.［18］严春临，张季，刘敏，等.星点设计-效应面法优化吴茱萸次碱固体脂质纳米粒处方［J］.中草药，2015，46（9）：1307-1313.［19］侯军.盐酸小檗碱固体脂质纳米粒的制备［D］.重庆：第三军医大学，2008.［20］周华锋，马全红，夏强，等.咪喹莫特固体脂质纳米粒的制备及其性能研究［J］.中国药学杂志，2006，41（7）：1084-1120.［21］Rompicharla SVK，Bhatt H，Shah A.Formulation optimization，characterization，and evaluation of in vitro cy⁃totoxic potential of Curcumin loaded solid lipidnanoparti⁃cles for improved anticancer activity［J］.Chemistry and Physics of Lipids，2017，208：10-18.［22］Elisabett，Esposito，et al.Progesterone lipid nanoparticles：scaling up and in vivo human study［J］.Pro⁃gesterone lipid nanoparticles：scaling up and in vivo human study，2017，119：437-446.［23］吕佳，刘冰，张振秋，等.苦参碱固体脂质纳米粒的制备［J］.中国实验方剂学杂志，2013，19（19）：61-63.［24］Mara Ferreira，Lu’sa Barreiros，Marcela A，et al.Topical co-delivery of methotrexate and etanercept using lipid nanoparticles：a targeted approach for Psoriasis man⁃agement［J］.Colloids and Surfaces B：Biointerfaces，2017，159：23-29.［25］Kamel M Kamel，Islam A Khalil，Mostafa E Rateb，et al.Chitosan-coated cinnamon/oregano-loaded sol⁃id lipid nanoparticles to augment 5-Fluorouracil cytotoxici⁃ty for colorectal cancer：extracts standardization，nanoparti⁃cles optimization and cytotoxicity evaluation［J］.Journal of Agricultural and Food Chemistry，2017，65（36）：7966-7981.［26］王馨.醋酸泼尼松龙固体脂质纳米粒研究［D］.重庆：重庆医科大学，2007.［27］Armin Sadighi，S.N.Ostad，S.M.Rezayat，et al.Mathematical modelling of the transport of hydroxypro⁃pyl-cyclodextrin inclusion complexes of ranitidine hydro⁃chloride and furosemide loaded chitosan nanoparticles across a Caco-2 cell monolayer［J］.Pharmaceutial Nantech⁃nology，2012，422：479-488.［28］梁健钦，刘华钢.白藜芦醇固体脂质纳米粒制备工艺及形态学研究［J］.中国实验方剂学杂志，2011，16（14）：28-30.［29］卞龙艳.柚皮素固体脂质纳米粒制剂的制备、表征及药动学评价［J］.中国新药杂志，2015，25（12）：1424-1430.［30］王敏，谢鹏，杨益，等.塞来昔布固体脂质纳米粒的制备及其在大鼠体内的药动学［J］.中国医院药学杂志，2015，35（1）：31-35.［31］邓艳平，刘岳金，戴雅彬，等.雷公藤内酯醇固体脂质纳米粒的制备及理化性质［J］.中国医院药学杂志，2017，37（9）：797-803.［32］邵红霞，奉建芳，尤晓英.脂质体包封率的测定方法［J］.中南药学，2009，7（3）：212-214.［33］胡连栋，唐星，崔福德.全反式维甲酸固体脂质纳米粒的制备及体内外评价［J］.药学学报，2005，40（1）：71-75.［34］Kuldeep Rajpoot，Sunil K Jain.Colorectal can⁃cer-targeted delivery of oxaliplatinvia folic acid-grafted sol⁃id lipid nanoparticles：preparation，optimization，and in vitro evaluation［J］.Artificial Cells，Nanomedicine，and Biotech⁃nology，2017，1：1-11. ［35］Filipa Lourenço Cardoso，Dora Brites，Maria Alex⁃andra Brito.Looking at theblood-brain barrier：Molecular anatomy and possible investigation approaches［J］.Brain Research Reviews，2010，64：328-363.［36］Ivona Brasnjevic，Harry W.M.Steinbusch，Chris⁃toph Schmitz，et al.Delivery of peptide and protein drugs over the blood-brain barrier［J］.Progress in Neurobiology，2009，87：212-251.［37］徐月红，徐莲英.脑靶向给药研究的进展［J］.中国药学杂志，2002，37（8）：569-573. ［38］Han HK，Amidon GL.Targeted prodrug design to optimize drug delivery［J］.AAPS PharmSci，2000，2（1）：E6.［39］张文静.富马酸喹硫平鼻用固体脂质纳米粒原位凝胶的制备及脑部靶向性的初步研究［D］.蚌埠：蚌埠医学院，2015.［40］Ma L，Fan Y，Wu H，et al.Tissue distribution and targeting evaluation of TMPafter oral administration of TMP-loaded microemulsion to mice［J］.Drug Dev Ind Pharm，2013，39（12）：1951-1958.［41］Afergan E，Epstein H，Dahan R，et al.Delivery of serotonin to the brain by monocytes following phagocytosis of liposomes［J］.Controlled Release，2008，132（2）：84-90.［42］周文斌，肖波，谢光洁.趋化因子与免疫介导的中枢神经系统炎性反应［J］.中国神经免疫学和神经病学杂志，2001，8（4）：231-233.［43］Tiwarisb，Amijimm.A review of nanocarrier-based CNS delivery systems［J］.Curr Drug Deliv，2006，3（2）：219-232.［44］Hu K，Li J，Shen ctoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery：in vi⁃tro and in vivo evaluations［J］.Control Release，2009，134（1）：55-61.［45］杨阳.文拉法辛固体脂质纳米粒的制备、药动学考察及其对脑组织P-糖蛋白的影响［D］.兰州：兰州大学，2013.。

张璇，赵文，高哲，等. 果胶与多酚相互作用机制及其对食品加工特性影响的研究进展[J]. 食品工业科技，2024，45（1）：378−386.doi: 10.13386/j.issn1002-0306.2023030201ZHANG Xuan, ZHAO Wen, GAO Zhe, et al. Research Progress on the Interaction Mechanism of Pectin and Polyphenol and Their Effect on Food Processing Characteristics[J]. Science and Technology of Food Industry, 2024, 45(1): 378−386. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023030201· 专题综述 ·果胶与多酚相互作用机制及其对食品加工特性影响的研究进展张　璇1，赵　文1,2，高　哲1，李美娇1，吴梦颖1，周　茜1,*（1.河北农业大学食品科技学院，河北保定 071000；2.河北省农产品加工工程技术研究中心，河北保定 071000）摘　要：果胶和多酚共存于植物性食品体系中。

除天然存在的果胶-多酚复合物外，在受到加热、高压、干燥等外力作用的食品加工过程中，两者会快速且自发地进行相互作用。

果胶与多酚之间的相互作用会影响食品的理化性质和功能特性。

本文总结了果胶与多酚相互作用的机制、内部和外部多重影响因素、主要的研究方法并结合 Langmuir 和Freundlich 常见的等温吸附模型对果胶与多酚之间的吸附行为进行描述和定量表征。

此外还探讨了两者相互作用对食品加工特性及多酚生物可利用性的影响，分析了该领域的研究方向和发展趋势。

关键词：果胶，多酚，相互作用，等温吸附模型，生物可利用性本文网刊:中图分类号：TS255.1 文献标识码：A 文章编号：1002−0306（2024）01−0378−09DOI: 10.13386/j.issn1002-0306.2023030201Research Progress on the Interaction Mechanism of Pectin and Polyphenol and Their Effect on Food Processing CharacteristicsZHANG Xuan 1，ZHAO Wen 1,2，GAO Zhe 1，LI Meijiao 1，WU Mengying 1，ZHOU Qian 1, *（1.College of Food Science and Technology, Hebei Agricultural University, Baoding 071000, China ；2.Engineering Technology Research Center for Agricultural Product Processing of Hebei, Baoding 071000, China ）Abstract ：The pectin and polyphenols that co-exist in plant-based food systems form complexes in natural conditions and interact quickly and spontaneously during food processing due to external forces, such as heating, high pressure, and drying.The interaction can affect the physicochemical properties and functional properties of foods. This review summarizes the mechanisms, multiple internal and external influencing factors, and main research methods involved in pectin and polyphenol interaction, while their adsorption behavior is described and quantitatively characterized using the isothermal adsorption model commonly used by Langmuir and Freundlich. In addition, the impact of pectin and polyphenol interaction on food processing characteristics and polyphenol bioavailability is also discussed, and the future research prospects and development trends in this field are analyzed.Key words ：pectin ；polyphenol ；interactions ；isothermal adsorption models ；bioavailability果胶是一种酸性杂多糖，广泛存在于蔬菜、水果和谷物等植物细胞壁中，在人类健康中发挥着重要的作用[1]。