文献类型：期刊文献

英文题名：Redox-responsive engineered hybrid nanomedicine for gallbladder cancer therapy via hyaluronic acid depletion

作者：Zou, Jinglin[1];Jiang, Cong[2];Li, Xianglong[1];Zhong, Tianyu[1];Wang, Shuqi[1];Wang, Bo[4];Zhang, Dapeng[1];Hao, Ji-Na[1];Cao, Yuanyuan[1];Guan, Mengjia[1];Zhang, Peng[2];Dai, Bin[3];Li, Yongsheng[1,3]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Frontier Sci Ctr Mat Biol & Dynam Chem, Shanghai Engn Res Ctr Hierarch Nanomat, Shanghai 200237, Peoples R China;[2]Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai 200092, Peoples R China;[3]Shihezi Univ, Sch Chem & Chem Engn, Key Lab Green Proc Chem Engn Xinjiang Bingtuan, Shihezi 832003, Peoples R China;[4]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Clin Lab, Shanghai 201900, Peoples R China

年份：2023

卷号：30

外文期刊名：APPLIED MATERIALS TODAY

收录：;EI(收录号：20225013230818);WOS:【SCI-EXPANDED(收录号:WOS:000976436500001)】；

基金：This work was financially supported by the National Natural Science Foundation of China (Nos. 51621002, 51972112, 52172279, 21805087, and 81972172) , Basic Research Program of Shanghai (21JC1406003 and 19JC1411700) , Leading Talents in Shanghai in 2018, Program of Shanghai Academic/Technology Research Leader (19XD1423200) , Shanghai Rising Star Program (21QA1402200) , and the Natural Science Foundation of Shanghai (21ZR1416600) . Animal experiments were executed according to the protocol approved by the Laboratory Animal Management Committee of East China University of Science and Technology (approval number: ECUST-2020-04001) . The authors would like to thank Prof. Yingbin Liu at Renji Hospital Affiliated to Shanghai Jiao Tong University for providing the GBC series cells.

语种：英文

外文关键词：Gallbladder cancer; Extracellular matrix; Hyaluronidase; Nanocarrier; Redox-responsive

摘要：Gallbladder cancer (GBC) is a highly fatal and most common biliary tract cancer for which there is no uniform chemotherapy regimen at present. Although several chemotherapy regimens are currently being examined in clinical trials, they are limited by the high systemic toxicity and low drug delivery efficiency. Based on the characteristics of the tumor microenvironment of GBC tumors that it is rich in hyaluronic acid (HA), herein, we design a paclitaxel (PTX)-loaded organosilica hybrid nanocarrier (named as PTX@PDHNs-HAase) modified with hyaluronidase (HAase), aiming to enhance the delivery and therapeutic efficiency of PTX in GBC tumors. Once the nanocarrier reaches the tumor site through the enhanced permeability and retention effect, HAase loaded onto the nanocarrier will degrade the excess HA presented at the GBC tumor site to cause its depletion, thereby softening the hard extracellular matrix (ECM) and facilitating further penetration of nanomedicine into the GBC tumor cells and releasing PTX under glutathione (GSH) stimulation to accomplish the chemotherapeutic effect. More importantly, PTX@PDHNs-HAase not only presents excellent therapeutic effect in vivo (tumor inhibition rate: 88.6%), but also reduces the systemic toxicity of PTX. To the best of our knowledge, this is the first exploration of the strategy to enhance the efficacy of chemotherapeutic agent for GBC tumor therapy by degrading HA to dismantle ECM for enhanced nanomedicine delivery, thus providing a promising paradigm for GBC treatment.