Li Xinming, Liu Peng
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People's Republic of China.
J Mater Chem B. 2022 Apr 13;10(15):2926-2932. doi: 10.1039/d2tb00150k.
Polyprodrugs with drugs as the structural units have been recognized as promising drug self-delivery systems (DSDSs) for tumor chemotherapy, especially ones in which the drug structural units are linked with both pH- and reduction-cleavable conjugations. However, stable DOX derivatives are released after the acid/reduction co-triggered degradation, exhibiting low antitumor efficacy due to their low solubility. Herein, a novel acid/reduction co-triggered degradable amphiphilic copolyprodrug was designed the facile polycondensation of an acid-labile dimer (D-DOX) and disulfide-containing monomer (DNC) with a PEGylated dimer (D-DOX-PEG) as an end-capping reagent. The resultant amphiphilic copolyprodrug (PDOX-PEG) with a high DOX content of 61.1% could easily self-assemble into nanoparticles around 154 nm in size, possessing excellent acid/reduction co-triggered DOX release and enhanced inhibition of tumor growth compared to free DOX towards HepG2 cells but showed good cytocompatibility towards L02 cells.
以药物为结构单元的聚前药已被公认为是用于肿瘤化疗的有前景的药物自递送系统（DSDSs），尤其是那些药物结构单元与pH和还原可裂解连接体相连的聚前药。然而，稳定的阿霉素衍生物在酸/还原共同触发降解后释放，由于其低溶解度而表现出低抗肿瘤疗效。在此，设计了一种新型的酸/还原共同触发可降解两亲性共聚前药，通过酸不稳定二聚体（D-DOX）和含二硫键单体（DNC）与聚乙二醇化二聚体（D-DOX-PEG）作为封端剂的简便缩聚反应制备。所得的两亲性共聚前药（PDOX-PEG）的阿霉素含量高达61.1%，能够轻松自组装成尺寸约为154 nm的纳米颗粒，与游离阿霉素相比，对肝癌细胞HepG2具有优异的酸/还原共同触发的阿霉素释放和增强的肿瘤生长抑制作用，但对L02细胞显示出良好的细胞相容性。
