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Reduction-Responsive Amphiphilic Star Copolymers with Long-chain Hyperbranched Poly(ε-caprolactone) Core and Disulfide Bonds for Trigger Release of Anticancer Drugs
European Polymer Journal ( IF 5.8 ) Pub Date : 2018-11-01 , DOI: 10.1016/j.eurpolymj.2018.09.014
Shan Zhang , Yinglai Hou , Heng Chen , Zijun Liao , Jianxin Chen , Ben B. Xu , Jie Kong

Abstract In this contribution, the reduction-responsive star copolymers with long-chain hyperbranched poly(e-caprolactone) (PCL) (HyperMacs) core and disulfide bonds were synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The HyperMacs core was constructed from disulfide-containing AB 2 -type PCL macromonomers, which possesses length-adjustable chain segments between branching points, large cavities, low degree of crystallinity, and reduction-responsivity. After grafted with poly(ethylene glycol), the reduction-responsive star copolymers can self-assemble into micelles in aqueous solution. The obtained micelles exhibited much lower critical micelle concentration (CMC) than their linear analogues. The reduction-responsivity from disulfide bonds makes them a promising carrier candidate for trigger release of anticancer drugs. The in vitro release results confirmed that their doxorubicin (DOX)-loaded micelles exhibited desirable reduction-triggered release performance. The cellular proliferation inhibition against HepG2 cells demonstrated that the DOX-loaded micelles showed a comparable anticancer activity with free DOX. Therefore, it can be expected that the reduction-sensitive micelles may serve as smart vehicles for intracellular delivery of anti-cancer drugs in tumour therapy.

中文翻译:

具有长链超支化聚(ε-己内酯)核和二硫键的还原响应两亲星形共聚物用于触发抗癌药物的释放

摘要 在这项贡献中,通过 Cu(I) 催化的叠氮化物-炔环加成 (CuAAC) 反应合成了具有长链超支化聚 (e-己内酯) (PCL) (HyperMacs) 核和二硫键的还原响应星形共聚物。HyperMacs 核心由含二硫化物的 AB 2 型 PCL 大分子单体构成,其在分支点之间具有长度可调的链段、大腔、低结晶度和还原响应性。与聚(乙二醇)接枝后,还原响应星形共聚物可以在水溶液中自组装成胶束。获得的胶束表现出比它们的线性类似物低得多的临界胶束浓度(CMC)。二硫键的还原反应性使它们成为触发释放抗癌药物的有希望的载体候选者。体外释放结果证实,它们的载有阿霉素 (DOX) 的胶束表现出理想的还原触发释放性能。对 HepG2 细胞的细胞增殖抑制表明,负载 DOX 的胶束显示出与游离 DOX 相当的抗癌活性。因此,可以预期还原敏感胶束可作为在肿瘤治疗中细胞内递送抗癌药物的智能载体。对 HepG2 细胞的细胞增殖抑制表明,负载 DOX 的胶束显示出与游离 DOX 相当的抗癌活性。因此,可以预期还原敏感胶束可作为在肿瘤治疗中细胞内递送抗癌药物的智能载体。对 HepG2 细胞的细胞增殖抑制表明,负载 DOX 的胶束显示出与游离 DOX 相当的抗癌活性。因此,可以预期还原敏感胶束可作为在肿瘤治疗中细胞内递送抗癌药物的智能载体。
更新日期:2018-11-01
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