Completely degradable backbone-type hydrogen peroxide responsive curcumin copolymer: synthesis and synergistic anticancer investigation
Completely degradable backbone-type hydrogen peroxide responsive curcumin copolymer: synthesis and synergistic anticancer investigation
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完全可降解骨架型过氧化氢响应姜黄素共聚物：合成及协同抗癌研究
DOI：
10.1039/c9py00892f
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发表时间：
2019-08-21
影响因子：
4.6
通讯作者：
Yin, Jun
中科院分区：
文献类型：
--
作者：
Qiao, Zhu;Liu, Huan-Ying;Yin, Jun
迄今为止，几种不同类型的聚合物基给药系统相继被开发出来。然而，大多数研究都集中在将药物物理包封到疏水胶束核心或通过可裂解的化学键将药物分子共价连接到侧链作为前药。本文中，使用姜黄素、短聚乙二醇链和草酰氯之间的缩聚反应，合成了含有骨架型姜黄素和草酸酯键的聚（姜黄素-共-草酸酯）共聚物。所得共聚物可通过过氧化氢（H2 O2）引发主链的完全降解释放活性治疗剂（姜黄素），使其成为理想的可控药物递送载体并适合于快速代谢。紫外-可见光谱和荧光光谱实验结果表明，由该共聚物制备的水分散性球形纳米粒在生理条件下稳定，但一旦暴露于外源性H2 O2则会逐渐解离。此外，在包封额外的抗癌药物（喜树碱; CPT）和近红外光热转换试剂（IR 780）后，CPT/IR 780@poly（curcumin-co-oxalate）复合物胶束形成，并且体外细胞测试表明它们是有效的协同化学-光热治疗单元。该工作填补了传统纳米载体设计的差距，并且这种H2 O2响应性具有巨大的潜力，以实现癌症诊断和治疗的功能协同性和适应性。
So far, several different kinds of polymer based drug delivery systems have been developed one after another. However, most of them were focused on physical encapsulation of drugs into hydrophobic micelle cores or covalently linked drug molecules to side chains as prodrugs through cleavable chemical bonds. Herein, using a polycondensation reaction between curcumin, short polyethylene glycol chains, and oxalyl chloride, a backbone-type curcumin and oxalate linkage containing poly(curcumin-co-oxalate) copolymer was synthesized. The resultant copolymer could release active therapeutic agents (curcumin) through hydrogen peroxide (H2O2) triggered complete degradation of the main chains, making them perfect controlled drug delivery vehicles and suitable for rapid metabolism. UV-vis and fluorescence experimental results demonstrated that the aqueous dispersible spherical nanoparticles formulated from such copolymers were stable under physiological conditions, but gradually dissociated once exposed to exogenous H2O2. Moreover, after encapsulating an additional anti-cancer drug (camptothecin; CPT) and a near infrared photothermal conversion reagent (IR780), CPT/IR780@poly(curcumin-co-oxalate) complex micelles were formed, and the in vitro cell test indicated that they were efficient synergistic chemo-photothermal therapy units. This work fills the gap of the conventional nanocarrier design, and such H2O2 responsiveness has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy.