Two-dimensional LDH nanodisks modified with hyaluronidase enable enhanced tumor penetration and augmented chemotherapy  

作　　者：Gaoming Li Yu Fan Lizhou Lin Rong Wu Mingwu Shen Xiangyang Shi 

机构地区：[1]State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,College of Chemistry,Chemical Engineering and Biotechnology,Donghua University,Shanghai 201620,China [2]Department of Ultrasound,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China

出　　处：《Science China Chemistry》2021年第5期817-826,共10页中国科学（化学英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81761148028,21773026,82001830);the National Key R&D Program(2017YFE0196200);the Science and Technology Commission of Shanghai Municipality(19XD1400100,19410740-200,20520710300);and the Shanghai Education Commission through the Shanghai Leading Talents Program.

摘　　要：The condensed tumor extracellular matrix(ECM)consisting of cross-linked hyaluronic acid(HA)is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penetration.Herein,we report a simple design of a hyaluronidase(HAase)-modified layered double hydroxide(LDH)nanoplatform loaded with anticancer drug doxorubicin(DOX)for enhanced tumor penetration and augmented chemotherapy.In our approach,LDH nanodisks were synthesized via a co-precipitation method,modified with HAase by electrostatic attraction,and finally physically loaded with DOX.The formulated DOX/LDH-HAase complexes show a high DOX loading percentage of 34.2%with good colloidal stability,retain 86.1%of the enzyme activity,and release DOX in a pH-responsive manner having a faster release rate under slightly acidic tumor microenvironment than that under a physiological condition.With the catalytic activity of HAase to digest the HA nearby the cancer cells,the developed DOX/LDH-HAase complexes enable more significant uptake by cancer cells and penetration in 3-dimensional tumor spheroids than enzyme-free DOX/LDH complexes,thus displaying much better antitumor efficacy in vitro than the latter.The more significant tumor penetration and inhibition of the DOX/LDH-HAase complexes than that of the DOX/LDH complexes was further demonstrated by in vivo tumor imaging and therapeutic activity assessments.Our study suggests a unique nanomedicine platform combined with both anticancer drug and enzyme for improved tumor penetration and chemotherapy,which is promising for effective chemotherapy of different types of stroma-rich tumors.

关 键 词：pancreatic cancer layered double hydroxide HYALURONIDASE tumor penetration CHEMOTHERAPY 

分 类 号：TQ460.4[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程]