Poor selectivity, low bioavailability and serious systemic side-effects have limited the application of traditional chemotherapy method for treatment of prostate cancer. Stimuli-responsive drug delivery systems for chemotherapy are mainly based on the unique characteristics of tumor microenvironment. In this study, the GSH-sensitive poly-TTG-SS@DTX NPs (DTX-loaded poly-Tetraethylene glycol nanoparticles) were designed and synthesized, which were characterized with nanosized diameter (92.8 ± 2.5 nm) and negatively charged surface charge (−24.7 ± 5.56 mV). Experiments in vitro showed that poly-TTG-SS@DTX NPs had good compatibility to healthy cells and strong anti-tumor effect because of rapid and sustained drug release of DTX from poly-TTG-SS@DTX NPs under the tumor-microenvironment condition. The cellular activity remained greater than 90% when the concentration of poly-TTG-SS NPs reached as high as 100 µg/mL treated on healthy cells. The killing effect of DTX loading NPs group on C4-2 cells was stronger than that of free anti-tumor drug and free DTX combined with the blank nano-carrier (25.21% vs 19.93% vs 20.96%). In conclusion, poly-TTG-SS@DTX NPs may provide a new therapeutic strategy for the chemotherapy of prostate cancer.

Graphical Abstract

中文翻译：

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用于治疗前列腺癌的肿瘤微环境响应纳米载体系统

传统化疗方法选择性差、生物利用度低以及严重的全身副作用限制了其在前列腺癌治疗中的应用。用于化疗的刺激响应性药物递送系统主要基于肿瘤微环境的独特特征。在本研究中，设计并合成了GSH敏感的聚TTG-SS@DTX NP（负载DTX的聚四乙二醇纳米颗粒），其特征在于纳米级直径（92.8±2.5 nm）和带负电的表面电荷（− 24.7±5.56毫伏）。体外实验表明，在肿瘤微环境条件下，poly-TTG-SS@DTX NPs能够快速、持续地释放DTX药物，因此与健康细胞具有良好的相容性和较强的抗肿瘤作用。当处理健康细胞的聚-TTG-SS NP 浓度高达 100 µg/mL 时，细胞活性仍保持在 90% 以上。DTX负载NPs组对C4-2细胞的杀伤作用强于游离抗肿瘤药物和游离DTX联合空白纳米载体(25.21% vs 19.93% vs 20.96%)。总之，聚TTG-SS@DTX NPs可能为前列腺癌的化疗提供新的治疗策略。

图形概要