A Novel Redox-Sensitive Drug Delivery System Based on Trimethyl-Locked Polycarbonate.
A Novel Redox-Sensitive Drug Delivery System Based on Trimethyl-Locked Polycarbonate.
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DOI：
10.1021/acs.biomac.3c00702
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发表时间：
2023-08
影响因子：
6.2
通讯作者：
Dongdong Wang;Mu Li;Hanning Zhang;Congshu Feng;Lili Wu;Lesan Yan
中科院分区：
文献类型：
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作者：
Dongdong Wang;Mu Li;Hanning Zhang;Congshu Feng;Lili Wu;Lesan Yan
刺激响应聚合物纳米载体能够利用肿瘤微环境的微妙变化来控制药物释放，在癌症治疗中引起了极大的关注。值得注意的是，NAD(P)H：醌氧化还原酶 1 (NQO1) 被发现在各种实体瘤中表达上调，由于其在生理条件下有效酶促还原三甲基锁定 (TML) 苯醌结构的能力，代表了一个有前途的治疗靶点。本研究合成了一种新型氧化还原敏感碳酸酯单体MTC，并通过开环聚合制备了其两亲性嵌段共聚物。通过成功自组装聚乙二醇-b-PMTC胶束，高效封装模型药物阿霉素（DOX）。胶束表现出氧化还原响应行为，导致药物快速释放。体外评估证实了它们优异的生物相容性和血液相容性。此外，抑制 NQO1 酶会减少 NQO1 过表达细胞中的药物释放，但不会减少对照细胞中的药物释放，从而导致 NQO1 酶抑制剂存在时细胞毒性降低。总体而言，这项研究展示了基于 MTC 的聚碳酸酯胶束在 NQO1 酶介导的肿瘤微环境中实现靶向和特异性药物释放的潜力。因此，基于 MTC 的聚合物自组装成纳米胶束作为药物输送应用中的智能纳米载体具有巨大的前景。
Stimuli-responsive polymer nanocarriers, capable of exploiting subtle changes in the tumor microenvironment for controlled drug release, have gained significant attention in cancer therapy. Notably, NAD(P)H: quinone oxidoreductase 1 (NQO1), found to be upregulated in various solid tumors, represents a promising therapeutic target due to its effective capability to enzymatically reduce trimethyl-locked (TML) benzoquinone structures in a physiological condition. In this study, a novel redox-sensitive carbonate monomer, MTC, was synthesized, and its amphiphilic block copolymers were prepared through ring-opening polymerization. By successfully self-assembling poly(ethylene glycol)-b-PMTC micelles, the model drug doxorubicin (DOX) was encapsulated with high efficiency. The micelles exhibited redox-responsive behavior, leading to rapid drug release. In vitro assessments confirmed their excellent biocompatibility and hemocompatibility. Furthermore, the inhibition of the NQO1 enzyme reduced drug release in NQO1-overexpressed cells but not in control cells, resulting in decreased cytotoxicity in the presence of NQO1 enzyme inhibitors. Overall, this study showcases the potential of MTC-based polycarbonate micelles to achieve targeted and specific drug release in the NQO1 enzyme-mediated tumor microenvironment. Therefore, the self-assembly of MTC-based polymers into nanomicelles holds immense promise as intelligent nanocarriers in drug delivery applications.