Dual-Responsive Doxorubicin-Conjugated Polymeric Micelles with Aggregation-Induced Emission Active Bioimaging and Charge Conversion for Cancer Therapy
作者:Xin Su、Boxuan Ma、Jun Hu、Tao Yu、Weihua Zhuang、Li Yang、Gaocan Li、Yunbing Wang
DOI:10.1021/acs.bioconjchem.8b00671
日期:2018.12.19
In recent years, intelligent polymeric micelles with multifunctions are in urgent demand for cancer diagnosis and therapy. Herein, pH and redox dual-responsive prodrug micelles with aggregation-induced emission (AIE) active cellular imaging and charge conversion have been prepared for combined chemotherapy and bioimaging based on a novel doxorubicin-conjugated amphiphilic PMPC-PAEMA-P (TPE-co-HD)-ss-P
近年来,对于癌症的诊断和治疗迫切需要具有多功能的智能聚合物胶束。在此,pH值和氧化还原具有聚合诱导的发射(AIE)活性细胞成像和电荷转换双响应前药胶束已经为联合化疗制备和生物成像基于新阿霉素缀合两亲PMPC-PAEMA-P(TPE-共- HD)-ss-P(TPE- co-HD)-PAEMA-PMPC共聚物。阿霉素通过pH可裂解的亚胺键结合,并且可以与谷胱甘肽(GSH)敏感的二硫键一起堆积在疏水核中。用pH响应的PAEMA作为“门”密封结合了DOX的内核,该门在药物释放和电荷转换介导的内吞作用加速后,在酸性条件下会迅速打开。有效内化后,高浓度的谷胱甘肽可裂解二硫键,从而进一步加速药物释放。同时,由于胶束的AIE行为,可以追踪细胞内药物递送。此外,在体外和体内对肿瘤的抑制作用都很大已经证明了这些DOX缀合的胶束。这种智能的前药胶束系统将是用于癌症治疗和生物成像的理想药物载体。