Development of effective tumor cell-targeted nanodrug formulations has been quite challenging, as many nanocarriers and targeting moieties exhibit nonspecific binding to cellular, extracellular, and intravascular components. We have developed a therapeutic nanoparticle formulation approach that balances cell surface receptor-specific binding affinity while maintaining minimal interactions with blood and tumor tissue components (termed "DART" nanoparticles), thereby improving blood circulation time, biodistribution, and tumor cell-specific uptake. Here, we report that paclitaxel (PTX)-DART nanoparticles directed to the cell surface receptor fibroblast growth factor-inducible 14 (Fn14) outperformed both the corresponding PTX-loaded, nontargeted nanoparticles and Abraxane, an FDA-approved PTX nanoformulation, in both a primary triple-negative breast cancer (TNBC) model and an intracranial model reflecting TNBC growth following metastatic dissemination to the brain. These results provide new insights into methods for effective development of therapeutic nanoparticles as well as support the continued development of the DART platform for primary and metastatic tumors.

中文翻译：

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用于原发性和转移性乳腺癌的非特异性粘附性、受体靶向治疗性纳米颗粒降低。

开发有效的肿瘤细胞靶向纳米药物制剂一直非常具有挑战性，因为许多纳米载体和靶向部分表现出与细胞、细胞外和血管内成分的非特异性结合。我们开发了一种治疗性纳米颗粒制剂方法，可平衡细胞表面受体特异性结合亲和力，同时保持与血液和肿瘤组织成分（称为“DART”纳米颗粒）的最小相互作用，从而改善血液循环时间、生物分布和肿瘤细胞特异性摄取。在这里，我们报告了针对细胞表面受体成纤维细胞生长因子诱导型 14 (Fn14) 的紫杉醇 (PTX)-DART 纳米颗粒的性能优于相应的负载 PTX 的非靶向纳米颗粒和 FDA 批准的 PTX 纳米制剂 Abraxane，在原发性三阴性乳腺癌 (TNBC) 模型和颅内模型中，反映了转移性扩散到大脑后 TNBC 的生长。这些结果为有效开发治疗性纳米颗粒的方法提供了新的见解，并支持继续开发针对原发性和转移性肿瘤的 DART 平台。