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负载阿霉素的光响应性胶束用于抑制骨肉瘤

Light-Responsive Micelles Loaded With Doxorubicin for Osteosarcoma Suppression.

作者信息

Chen Jiayi, Qian Chenhong, Ren Peng, Yu Han, Kong Xiangjia, Huang Chenglong, Luo Huanhuan, Chen Gang

机构信息

Bengbu Medical College, Bengbu, China.

Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

出版信息

Front Pharmacol. 2021 Jun 18;12:679610. doi: 10.3389/fphar.2021.679610. eCollection 2021.

Abstract

The enhancement of tumor targeting and cellular uptake of drugs are significant factors in maximizing anticancer therapy and minimizing the side effects of chemotherapeutic drugs. A key challenge remains to explore stimulus-responsive polymeric nanoparticles to achieve efficient drug delivery. In this study, doxorubicin conjugated polymer (Poly-Dox) with light-responsiveness was synthesized, which can self-assemble to form polymeric micelles (Poly-Dox-M) in water. As an inert structure, the polyethylene glycol (PEG) can shield the adsorption of protein and avoid becoming a protein crown in the blood circulation, improving the tumor targeting of drugs and reducing the cardiotoxicity of doxorubicin (Dox). Besides, after ultraviolet irradiation, the amide bond connecting Dox with PEG can be broken, which induced the responsive detachment of PEG and enhanced cellular uptake of Dox. Notably, the results of immunohistochemistry showed that Poly-Dox-M had no significant damage to normal organs. Meanwhile, they showed efficient tumor-suppressive effects. This nano-delivery system with the light-responsive feature might hold great promises for the targeted therapy for osteosarcoma.

摘要

增强药物的肿瘤靶向性和细胞摄取是最大化抗癌治疗效果并最小化化疗药物副作用的重要因素。探索刺激响应性聚合物纳米颗粒以实现高效药物递送仍然是一个关键挑战。在本研究中,合成了具有光响应性的阿霉素共轭聚合物(Poly-Dox),其在水中可自组装形成聚合物胶束(Poly-Dox-M)。作为一种惰性结构,聚乙二醇(PEG)可屏蔽蛋白质吸附并避免在血液循环中形成蛋白冠,从而提高药物的肿瘤靶向性并降低阿霉素(Dox)的心脏毒性。此外,紫外线照射后,连接Dox与PEG的酰胺键可断裂,这诱导了PEG的响应性脱离并增强了Dox的细胞摄取。值得注意的是,免疫组织化学结果表明Poly-Dox-M对正常器官无明显损伤。同时,它们显示出有效的肿瘤抑制作用。这种具有光响应特性的纳米递送系统可能对骨肉瘤的靶向治疗具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3210/8249570/7801fd65c0c6/fphar-12-679610-g007.jpg

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