Targeting ability of systemically administered drug-loaded polymeric micelles against lymph node metastasis

肿瘤扩散到远处器官和淋巴结是癌症最具威胁性的方面。目前针对淋巴转移的治疗策略显示出低效率和高发病率。在这里，评价系统给药聚合物胶束的靶向能力，以开发一种有效的治疗淋巴转移的方法。因此，将生物发光的小鼠黑色素瘤B16-F10-Luc细胞注射到小鼠的前爪中，通过聚乙二醇b-聚谷氨酸共聚物的羧基部分与奥沙利铂的母体(1，2-二氨基环己烷)铂(II)形成络合物来制备胶束，从而建立了早期淋巴结转移的模型。无论原发肿瘤是否存在，胶束均在转移的淋巴结内聚集，达到显著的抗肿瘤效果。此外，胶束的大小影响其对淋巴结转移的靶向能力，因为直径为30 nm的胶束比直径为70 nm的胶束更有效。这种大小效应也被观察到对人硬化性胃癌生物发光原位模型的淋巴转移的影响。30 nm胶束靶向淋巴结转移的能力可能为早期诊断和有效治疗提供新的途径。

Tumor spread to distant organs and lymph nodes is the most threatening aspect of cancer. Current therapeutic strategies against lymphatic metastases show low efficiency and high morbidity. Here, the targeting ability of systemically administered drug-loaded polymeric micelles against lymph node metastasis was evaluated for developing an efficacious therapy against lymphatic metastasis. Thus, a model of early lymph node metastasis was developed by using bioluminescent murine melanoma B16-F10-Luc cells, injected in the forepaw of mice, while the micelles were prepared by the complex formation between the carboxylic moieties of PEG-b-poly(glutamic acid) copolymer and (1,2-diaminocyclohexane) platinum(II), the parent complex of oxaliplatin. Micelles accumulated in metastatic lymph nodes regardless of the presence of primary tumor, achieving significant antitumor effect. Moreover, the size of the micelle affected their targeting ability against lymph node metastasis, as micelles with 30-nm diameter were more efficient than micelles with 70-nm diameter. This size effect was also observed against the lymph node metastasis of a bioluminescent orthotopic model of human scirrhous gastric cancer. The ability of 30-nm micelles to target lymph node metastases may provide a novel approach for early diagnosis and efficient therapy.