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Design of DOX-GNRs-PNIPAM@PEG-PLA Micelle With Temperature and Light Dual-Function for Potent Melanoma Therapy
Frontiers in Chemistry ( IF 5.5 ) Pub Date : 2020-11-19 , DOI: 10.3389/fchem.2020.599740
Na Wang , Jing Shi , Cong Wu , Weiwei Chu , Wanru Tao , Wei Li , Xiaohai Yuan

Objective: The aim of this study was to construct light and temperature dual-sensitive micellar carriers loaded with doxorubicin (DOX) and gold nanorods (DOX-GNRs-PNIPAM@PEG-PLA, DAPP) for melanoma therapy.

Methods: The DAPP self-assembled using fine-tuned physicochemical properties in water. The DAPP structure, temperature- and photo-sensitivity, drug-release, in-vitro serum stability, and cytotoxicity against melanoma B16F10 cells were evaluated in detail. The corresponding in-vitro and in-vivo therapeutic mechanisms were then evaluated using a B16F10-melanoma bearing BALB/c nude mouse model (B16F10).

Results: The light and temperature sensitive micellar drug-delivery system assembled from block copolymer and gold nanorods exhibited a narrow particle size and size distribution, good biocompatibility, well-designed photo-temperature conversion, controlled drug release, and high serum stability. Compared with the free DOX- and PBS-treated groups, the cell endocytosis-mediated cytotoxicity and intra-tumor accumulation of DAPP was markedly enhanced by the NIR-light exposure and induced potent in-vivo tumor inhibitory activity.

Conclusion: The design of DAPP, a dual-functional micellar drug-delivery system with temperature- and light-sensitive properties, offers a new strategy for skin-cancer therapy with a potent therapeutic index.



中文翻译:

温光双重功能的DOX-GNRs-PNIPAM @ PEG-PLA胶束设计用于有效的黑色素瘤治疗

目的: 这项研究的目的是构建载有阿霉素(DOX)和金纳米棒(DOX-GNRs-PNIPAM @ PEG-PLA,DAPP)的光和温度双敏感胶束载体,用于黑色素瘤治疗。

方法:DAPP使用微调后的理化性质在水中自组装。DAPP结构,温度和光敏性,药物释放,体外详细评估了血清稳定性和对黑色素瘤B16F10细胞的细胞毒性。相应的体外体内 然后使用带有B16F10黑色素瘤的BALB / c裸鼠模型(B16F10)评估治疗机制。

结果:由嵌段共聚物和金纳米棒组装而成的对光和温度敏感的胶束药物递送系统显示出窄的粒径和尺寸分布,良好的生物相容性,精心设计的光温转换,可控的药物释放和高的血清稳定性。与游离DOX和PBS处理的组相比,NAPP暴露和诱导的强力显着增强了细胞内吞介导的DAPP的细胞毒性和肿瘤内积累体内 肿瘤抑制活性。

结论: DAPP是一种具有温度和光敏特性的双功能胶束药物递送系统,其设计为具有有效治疗指数的皮肤癌治疗提供了新的策略。

更新日期:2021-01-05
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