纳米载体
胶束
化学
乙二醇
药物输送
生物相容性
组合化学
两亲性
控制释放
药品
生物物理学
共聚物
纳米技术
聚合物
材料科学
有机化学
药理学
水溶液
生物
医学
作者
Dongdong Wang,Mu Li,Hanning Zhang,Congshu Feng,Lili Wu,Lesan Yan
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2023-08-16
卷期号:24 (9): 4303-4315
标识
DOI:10.1021/acs.biomac.3c00702
摘要
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.
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