We report a new reduction-responsive amphiphilic polymeric prodrug based on a linear dextran (DEX) backbone, which was conjugated with an hydrophobic camptothecin (CPT) prodrug block and an hydrophilic poly[poly(ethylene glycol) methyl ether methacrylate] (POEGMA) block [DEX-PCPT-b-POEGMA (DCO)] by atom transfer radical polymerization (ATRP). This amphiphilic prodrug has a unique molecular structure with prominent features, including strong practicability for methacrylate prodrug monomer, high drug loading rate (up to 23 wt%), adjustable proportion of hydrophobic and hydrophobic portions, superior stability in aqueous solution, and easy access to cells. Introduction of a disulfide bond linker between the drug and the carrier can realize the function of reduction-responsive controlled drug-release. The experimental study indicated that the prodrug exhibited notable antitumor activity against HeLa cells and MCF-7 cells in vitro. Compared to similar DCO prodrug based on double carbon bond, the disulfide bond-conjugated DCO prodrug induced higher level of tumor cell apoptosis. Considering the drug-loading efficiency, micellar stability, cost of preparation and controlled drug release, the presented prodrug is more advantageous than traditional unimolecular prodrug and represents a promising approach for design of stimuli-responsive polymeric prodrug for effective cancer therapeutics.

我们报告了一种新的基于线性右旋糖酐（DEX）主链的还原反应性两亲聚合物前药，该药物与疏水性喜树碱（CPT）前药嵌段和亲水性聚[聚（乙二醇）甲基醚甲基丙烯酸甲酯]（POEGMA）嵌段共轭[DEX-PCPT- b-POEGMA（DCO）]通过原子转移自由基聚合（ATRP）。这种两亲性前药具有独特的分子结构，具有突出的特征，包括对甲基丙烯酸酯前药单体的强实用性，较高的载药率（最高23 wt％），疏水性和疏水性部分的比例可调节，在水溶液中具有出色的稳定性以及易于获得细胞。在药物和载体之间引入二硫键连接子可以实现还原反应控制药物释放的功能。实验研究表明，该前药在体外对HeLa细胞和MCF-7细胞具有显着的抗肿瘤活性。与基于双碳键的类似DCO前药相比，二硫键结合的DCO前药可诱导更高水平的肿瘤细胞凋亡。考虑到载药效率，