Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer  

作　　者：Wen Ma Qiling Chen Weiguo Xu Meng Yu Yuanyuan Yang Binhua Zou Yu Shrike Zhang Jianxun Ding Zhiqiang Yu 

机构地区：[1]Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China [2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun,130022,China [3]Division of Engineering in Medicine,Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,Cambridge,MA,02139,USA

出　　处：《Nano Research》2021年第3期846-857,共12页纳米研究（英文版）

基　　金：This study was financially supported by the National Key Research and Development Program of China(No.2016YFC1100701);the National Natural Science Foundation of China(Nos.52022095,51973216,and 51873207);the Science and Technology Development Program of jilin Province(No.20200404182YY);the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019005)。

摘　　要：Multidrug-resistance(MDR)featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic.Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR.However,the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites.In the present study,a type of self-targeting hyaluronate(HA)nanogels((CDDPH)^ANG/DOX)to reverse drug resistance through the synchronized pharmacokinetics,intratumoral distribution,and intracellular release of topoisomerase II inhibitor doxorubicin(DOX)and DNA-crosslinking agent cisplatin(CDDP)is developed.With prolonged circulation time and enhanced intratumoral accumulation in vivo,(CDDP)^HANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity.Besides,fluorescence imaging of DOX combined with the micro-computed tomography(micro-CT)imaging of CDDP facilitates the visualization of this combination tumor chemotherapy.With visualizable synchronized drug delivery,the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.

关 键 词：hyaluronate nanogel self-targetability intracellular drug codelivery multimodal imaging reversal of multidrug resistance 

分 类 号：TQ427.26[化学工程] R737.9[医药卫生—肿瘤]