State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
J Control Release. 2015 Apr 28;204:11-9. doi: 10.1016/j.jconrel.2015.01.039. Epub 2015 Jan 31.
The biomimetic delivery system (BDS) based on special types of endogenous cells like macrophages and T cells, has been emerging as a novel strategy for cancer therapy, due to its tumor homing property and biocompatibility. However, its development is impeded by complicated construction, low drug loading or negative effect on the cell bioactivity. The present report constructed a BDS by loading doxorubicin (DOX) into a mouse macrophage-like cell line (RAW264.7). It was found that therapeutically meaningful amount of DOX could be loaded into the RAW264.7 cells by simply incubation, without significantly affecting the viability of the cells. Drug could release from the BDS and maintain its activity. RAW264.7 cells exhibited obvious tumor-tropic capacity towards 4T1 mouse breast cancer cells both in vitro and in vivo, and drug loading did not alter this tendency. Importantly, the DOX loaded macrophage system showed promising anti-cancer efficacy in terms of tumor suppression, life span prolongation and metastasis inhibition, with reduced toxicity. In conclusion, it is demonstrated that the BDS developed here seems to overcome some of the main issues related to a BDS. The DOX loaded macrophages might be a potential BDS for targeted cancer therapy.
基于特殊类型的内源性细胞(如巨噬细胞和 T 细胞)的仿生递药系统(BDS),由于其肿瘤归巢特性和生物相容性,已成为癌症治疗的一种新策略。然而,其发展受到复杂结构、低载药量或对细胞生物活性的负面影响的阻碍。本报告通过将阿霉素(DOX)载入小鼠巨噬细胞样细胞系(RAW264.7)构建了一种 BDS。结果发现,通过简单孵育即可将治疗意义上数量的 DOX 载入 RAW264.7 细胞,而不会显著影响细胞活力。药物可以从 BDS 中释放并保持其活性。RAW264.7 细胞在体外和体内均表现出对 4T1 小鼠乳腺癌细胞的明显肿瘤趋向性,而药物载入并未改变这种趋势。重要的是,载 DOX 巨噬细胞系统在抑制肿瘤、延长寿命和抑制转移方面表现出有希望的抗癌疗效,同时降低了毒性。总之,研究结果表明,这里开发的 BDS 似乎克服了与 BDS 相关的一些主要问题。载 DOX 巨噬细胞可能是一种有潜力的靶向癌症治疗的 BDS。