美国发明三阴性乳腺癌双靶脂质体脂质体是具有靶向给药功能的新型纳米颗粒，利用磷脂双层膜包裹药物分子而成，由于细胞膜的基本结构也是磷脂双层膜，故脂质体有很好的生物相容性。
如果将靶向物质掺入脂质体膜，脂质体可以向特定部位靶向集中，即主动靶向型脂质体。
此外，脂质体还可延长药物作用时间、减少药物毒性、提高药物稳定性。
不过，如何区分恶性肿瘤细胞和非恶性肿瘤细胞是脂质体药物的主要挑战，尤其对于不表达雌激素受体、孕激素受体、HER2的三阴性乳腺癌。
2019年3月20日，美国科学促进会《科学》旗下《科学进展》在线发表哈佛大学医学院、波士顿儿童医院、纽约市立学院的研究报告，开发了一种互补靶向策略，通过精确匹配多价配体受体相互作用，可以识别并靶向原发部位和转移病灶的三阴性乳腺癌，有效抑制三阴性乳腺肿瘤的进展和转移。
该研究首先筛选了一组三阴性乳腺癌细胞表面标志物，并且确定了细胞间黏附分子-1（ICAM1）和上皮生长因子受体（EGFR）作为三阴性乳腺癌互补靶向的最佳候选靶点。
随后，该研究设计了一种双靶互补脂质体，可以精准匹配三阴性乳腺癌细胞表面特定ICAM1和EGFR分子比例和组织。
体外机制分析表明，双靶互补脂质体与单靶脂质体相比，结合细胞能力提高、进入细胞作用增强、受体信号转导减少。
原位和肺转移模型分析表明，双靶互补脂质体可以显著提高化疗药物多柔比星（阿霉素）的肿瘤靶向活性和抗肿瘤效果。
同时，可以延长化疗药物作用时间、减少化疗药物毒性、提高化疗药物稳定性。
因此，该研究结果表明，双靶互补脂质体有望成为设计三阴性乳腺癌个体化纳米药物的平台技术。
Sci Adv. 2019 Mar 20;5(3):eaav5010.Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis.Peng Guo, Jiang Yang, Daxing Liu, Lan Huang, Gillian Fell, Jing Huang, Marsha A. Moses, Debra T. Auguste.Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The City College of New York, New York, NY, USA.Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule-1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC.DOI: 10.1126/sciadv.aav5010。
