Triple negative breast cancer (TNBC) is difficult to treat effectively, due to its aggressiveness, drug resistance, and lack of the receptors required for hormonal therapy, particularly at the metastatic stage. Here, we report the development and evaluation of a multifunctional nanoparticle formulation containing an iron oxide core that can deliver doxorubicin, a cytotoxic agent, and polyinosinic:polycytidylic acid (Poly IC), a TLR3 agonist, in a targeted and simultaneous fashion to both breast cancer and dendritic cells. Endoglin-binding peptide (EBP) is used to target both TNBC cells and vasculature endothelium. The nanoparticle demonstrates favorable physicochemical properties and a tumor-specific targeting profile. The nanoparticle induces tumor apoptosis through multiple mechanisms including direct tumor cell killing, dendritic cell-initiated innate and T cell-mediated adaptive immune responses. The nanoparticle markedly inhibits tumor growth and metastasis and substantially extends survival in an aggressive and drug-resistant metastatic mouse model of TNBC. This study points to a promising platform that may substantially improve the therapeutic efficacy for treating metastatic TNBC.

三阴性乳腺癌（TNBC）由于其侵袭性、耐药性以及缺乏激素治疗所需的受体（尤其是在转移阶段）而难以有效治疗。在这里，我们报告了一种含有氧化铁核心的多功能纳米颗粒制剂的开发和评估，该制剂可以以靶向且同时的方式将阿霉素（一种细胞毒剂）和聚肌苷酸：聚胞苷酸（Poly IC）（一种 TLR3 激动剂）递送至双侧乳房癌症和树突状细胞。内皮糖蛋白结合肽 (EBP) 用于靶向 TNBC 细胞和脉管系统内皮。该纳米颗粒表现出良好的理化特性和肿瘤特异性靶向特性。纳米颗粒通过多种机制诱导肿瘤细胞凋亡，包括直接杀死肿瘤细胞、树突状细胞发起的先天性和 T 细胞介导的适应性免疫反应。该纳米颗粒可显着抑制肿瘤生长和转移，并显着延长侵袭性和耐药性 TNBC 转移性小鼠模型的生存期。这项研究指出了一个有前景的平台，可以显着提高转移性​​ TNBC 的治疗效果。