Preparation of polyethylene glycol-polyacrylic acid block copolymer micelles with pH/hypoxic dual-responsive for tumor chemoradiotherapy.,Colloids and Surfaces B: Biointerfaces

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Preparation of polyethylene glycol-polyacrylic acid block copolymer micelles with pH/hypoxic dual-responsive for tumor chemoradiotherapy.
Colloids and Surfaces B: Biointerfaces ( IF 5.4 ) Pub Date : 2020-03-04 , DOI: 10.1016/j.colsurfb.2020.110943
Jiajia Weng ₁ , Zhongbing Huang ₁ , Ximing Pu ₁ , Xianchun Chen ₁ , Guangfu Yin ₁ , Yaping Tian ₁ , Ying Song ₂

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Block copolymers of poly(ethylene glycol)-poly(acrylic acid) linked with metronidazole (MN-PAA-PEG) were prepared via carbodiimide and esterification methods, and self-assembled into core-shell micelles as nano radiosensitizers and carriers of doxorubicin (DOX) delivery. These DOX/MN-PAA-PEG micelles exhibited good pH value and hypoxia dual-responsive properties via analyzing the change of micelle size and drug‒release behavior under hypoxia humor condition. The results of the cell test indicated that DOX was efficiently delivered by DOX/MN-PAA-PEG micelles into the cell nuclei. Compared to 22.4 % of their DOX release under pH 7.4, the rate of DOX release from DOX/MN-PAA-PEG micelles under reducing condition (pH 5.0) was up to 55.9 %. DOX-loaded micelles under 600 MU electron radiation and hypoxia induced the rapidest apoptosis of the tumor-cells, indicating the synergistic effect of their radiotherapy and chemotherapy from the prepared micelles. In vivo investigation and fluorescence imaging revealed that MN-PAA-PEG possessed no toxicity on main organs, and DOX/MN-PAA-PEG micelles were mainly accumulated in the tumor site at 10 h of post-injection, suggesting their good passive tumor-targeted effect. These results suggested that DOX/MN-PAA-PEG micelles were promising candidates for chemoradiotherapy on tumor.

中文翻译：

pH /低氧双重反应的聚乙二醇-聚丙烯酸嵌段共聚物胶束的制备用于肿瘤放化疗。

通过碳二亚胺和酯化法制备了与甲硝唑（MN-PAA-PEG）连接的聚乙二醇-聚丙烯酸嵌段共聚物，并自组装成核壳胶束作为纳米放射增敏剂和阿霉素载体（DOX））交货。通过分析低氧幽默条件下胶束大小的变化和药物释放行为，这些DOX / MN-PAA-PEG胶束表现出良好的pH值和低氧双重反应特性。细胞测试的结果表明，DOX被DOX / MN-PAA-PEG胶束有效地传递到细胞核中。与在pH 7.4下其DOX释放量的22.4％相比，在还原条件（pH 5.0）下DOX / MN-PAA-PEG胶束中DOX释放率高达55.9％。负载DOX的胶束在600 MU电子辐射和缺氧条件下诱导了最快的肿瘤细胞凋亡，表明它们从制备的胶束中进行放疗和化疗的协同作用。体内研究和荧光成像显示，MN-PAA-PEG对主要器官无毒性，而DOX / MN-PAA-PEG胶束主要在注射后10 h聚集在肿瘤部位，表明它们具有良好的被动性有针对性的效果。这些结果表明，DOX / MN-PAA-PEG胶束有望用于肿瘤放化疗。

更新日期：2020-03-04

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