The design and synthesis of dextran-doxorubicin prodrug-based pH-sensitive drug delivery system for improving chemotherapy efficacy  

作　　者：Xiaoli Zhang Tian Zhang Xianbin Ma Yajun Wang Yi Lu Die Jia Xiaohua Huang Jiucun Chen Zhigang Xu Feiqiu Wena 

机构地区：[1]Department of Hematology and Oncology,Shenzhen Children’s Hospital,Shenzhen 518038,China [2]School of Materials and Energy,Southwest University,Chongqing 400715,China [3]Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices,Chongqing 400715,China [4]Guangan Changming Research Institute for Advanced Industrial Technology,Guangan 638500,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2020年第5期605-616,共12页亚洲药物制剂科学（英文）

基　　金：supported by Science and Technology Project from the Science Technology and Innovation Committee of Shenzhen Municipality(JCYJ20170817170110940 and JCJY20170307163529489);the Sichuan Science and Technology Program(2018JY0392 and 2018GZYZF0008);Sanming Project of Medicine in Shenzhen(SZSM201512033);Shenzhen Public Service Platform of Molecular Medicine in Pediatric Hematology and Oncology。

摘　　要：Tumor cells show acidic conditions compared with normal cells,which further inspires scientist to build nanocarrier responsive to tumor microenvironment(TME)for enhancing tumor therapeutic efficacy.Here,we report a pH-sensitive and biocompatible polyprodrug based on dextran-doxorubicin(DOX)prodrug(DOXDT)for enhanced chemotherapy.Highdensity DOX component was covalently decorated on the nanocarrier and the drug molecules could be effectively released in the acidic tumor tissue/cells,improving chemotherapy efficacy.Specifically,a dextran-based copolymer was preliminarily prepared by one-step atom transfer radical polymerization(ATRP);then DOX was conjugated on the copolymer component via pH-responsive hydrazone bond.The structure of DOXDT can be well-controlled.The resulting DOXDT was able to further self-assemble into nanoscale micelles with a hydration diameter of about 32.4 nm,which presented excellent micellar stability.Compared to lipid-based drug delivery system,the DOXDT prodrug showed higher drug load capacity up to 23.6%.In addition,excellent stability and smaller size of the nanocarrier contributed to better tissue permeability and tumor suppressive effects in vivo.Hence,this amphipathic DOXDT prodrug is promising in the development of translational DOX formulations,which would be widely applied in cancer therapy.

关 键 词：DEXTRAN CHEMOTHERAPY PRODRUG Tumor acidic microenvironment Controlled release 

分 类 号：R943[医药卫生—药剂学]