Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments
Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments
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DOI：
10.1002/adfm.201804227
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发表时间：
2018-08
影响因子：
19
通讯作者：
Wen Sun;Yan Wen;R. Thiramanas;Mingjia Chen;Jianxiong Han;N. Gong;M. Wagner;Shuai Jiang;
中科院分区：
文献类型：
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作者：
Wen Sun;Yan Wen;R. Thiramanas;Mingjia Chen;Jianxiong Han;N. Gong;M. Wagner;Shuai Jiang;
传统的光动力疗法对于抗癌治疗是无效的，因为实体肿瘤具有缺氧的微环境。基于光响应聚合物的光活化化学疗法的发展可以在“治疗窗口”中被光激活，这将为基础研究提供新的方法，并允许在缺氧条件下进行抗癌光疗。这项工作合成了一种新型含钌嵌段共聚物，用于缺氧肿瘤环境中的光活化化疗。该聚合物具有亲水性聚（乙二醇）嵌段和疏水性含Ru嵌段，其含有红光可裂解（650-680 nm）的药物-Ru络合物缀合物。嵌段共聚物自组装成胶束，可以被癌细胞有效地吸收。红光诱导药物-Ru络合物缀合物从胶束中释放，并且该过程是不依赖于氧的。释放的缀合物甚至在缺氧肿瘤环境中也抑制肿瘤细胞生长。此外，将含Ru聚合物用于荷瘤小鼠模型中的光活化化疗。聚合物胶束的光活化化疗显示出有效的肿瘤生长抑制。此外，聚合物胶束在治疗过程中不会对小鼠造成任何毒副作用，表明该系统对血液和健康组织具有良好的生物相容性。新型红光响应性含Ru聚合物为针对缺氧肿瘤的光疗提供了新平台。
Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer self‐assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug–Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru‐containing polymer for photoactivated chemotherapy in a tumor‐bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red‐light‐responsive Ru‐containing polymer provides a new platform for phototherapy against hypoxic tumors.