2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy  

作　　者：Yunjie Xu Yingwei Wang Jusung An Adam C.Sedgwick Mingle Li Jianlei Xie Weibin Hu Jianlong Kang Sajal Sen Axel Steinbrueck Bin Zhang Lijun Qiao Swelm Wageh Jonathan F.Arambula Liping Liu Han Zhang Jonathan L.Sessler Jong Seung Kim 

机构地区：[1]Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics,International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education,Shenzhen Institute of Translational Medicine,Department of Otolaryngology,Shenzhen Second People’s Hospital,The First Affiliated Hospital,College of Optoelectronic Engineering,Shenzhen University,Shenzhen,518060,China [2]Department of Chemistry,Korea University,Seoul,02841,South Korea [3]Department of Hepatobiliary and Pancreatic Surgery,Shenzhen People’s Hospital,Second Clinical Medical College of Jinan University,Shenzhen,518020,China [4]Department of Chemistry,The University of Texas at Austin,Austin,TX,78712-1224,USA [5]Hunan Key Laboratory of Nanophotonics and Devices,School of Physics and Electronics,Central South University,932 South Lushan Road,Changsha,410083,China [6]Institute of Translation Medicine Shenzhen Second People’s Hospital First Affiliated Hospital of Shenzhen University,Shenzhen,518035,China [7]Department of Physics,Faculty of Science,King Abdulaziz University,Jeddah,21589,Saudi Arabia

出　　处：《Bioactive Materials》2022年第8期76-85,共10页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant No.11904239,Y.W.W);the Creative Research Initiative of National Research Foundation of Korea(NRF)(CRI project No.2018R1A3B1052702,J.S.K.);Initial support for the work in Austin came from the National Institutes of Health(CA 68682 to J.L.S.)with subsequent funding from the Robert A.Welch Foundation(F-0018 to J.L.S.);supported by Brain Pool Program through the funded by the Ministry of Science and ICT(Grant No.2020H1D3A1A02080172,M.L.).

摘　　要：An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

关 键 词：2D MXene NANOMEDICINE PRODRUG Iron chelation Photothermal therapy 

分 类 号：R73[医药卫生—肿瘤]