文献类型：期刊文献

英文题名：A "Valve-Closing" Starvation Strategy for Amplification of Tumor-Specific Chemotherapy

作者：Li, Xianglong[1];Jiang, Cong[2];Wang, Qinghua[1];Yang, Shaobo[1];Cao, Yuanyuan[1];Hao, Ji-Na[1];Niu, Dechao[1];Chen, Yan[2];Han, Bo[3];Jia, Xin[4];Zhang, Peng[2];Li, Yongsheng[1,3,4]

机构：[1]East China Univ Sci & Technol, Frontier Sci Ctr Mat Biol & Dynam Chem, Shanghai Engn Res Ctr Hierarch Nanomat,Key Lab Ul, Minist Educ,Sch Mat Sci & Engn,Lab Low Dimens Mat, Shanghai 200237, Peoples R China;[2]Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Thorac Surg, Shanghai 200092, Peoples R China;[3]Shihezi Univ, Sch Pharm, Minist Educ, Key Lab Xinjiang Endem Phytomed Resources, Shihezi 832003, Peoples R China;[4]Shihezi Univ, Key Lab Green Proc Chem Engn Xinjiang Bingtuan, Sch Chem & Chem Engn, Shihezi 832003, Peoples R China

年份：2022

卷号：9

期号：8

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20220311472108);WOS:【SCI-EXPANDED(收录号:WOS:000743188300001)】；

基金：X.L. and C.J. contributed equally to this work. 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), the Natural Science Foundation of Shanghai (21ZR1416600), the 111 project (B14018), and Programs of Shanghai Pulmonary Hospital (FKCX1904). 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).

语种：英文

外文关键词：differential stress sensitization; glucose metabolism; GLUT1 inhibition; stability-controllable nanomedicines; starvation-sensitized chemotherapy

摘要：Starvation-dependent differential stress sensitization effect between normal and tumor cells provides a potentially promising strategy to amplify chemotherapy effects and reduce side effects. However, the conventional starvation approaches such as glucose oxidase (Gox)-induced glucose depletion and nanomedicine-enabled vascular embolism usually suffer from aggravated tumor hypoxia, systemic toxicity, and unpredictable metabolic syndrome. Herein, a novel "valve-closing" starvation strategy is developed to amplify the chemotherapy effects via closing the "valve" of glucose transported into tumor cells, which is accomplished by a glucose transporters 1 (GLUT1, valve of glucose uptake) inhibitor (Genistein, Gen) and chemotherapeutic agent (Curcumin, Cur) coloaded hybrid organosilica-micelles nanomedicine (designated as (Gen + Cur)@FOS) with controllable stability. In vitro and in vivo results demonstrate that (Gen + Cur)@FOS can effectively reduce glucose/adenosine triphosphate levels in tumor cells by inhibiting GLUT1 expression (i.e., "valve-closing") to induce the starvation of tumor cells, thus weakening the resistance of tumor cells to apoptosis caused by chemotherapy, and consequently contributing to the remarkably improved antitumor efficiency and minimized side effects based on the stress sensitization effect mediated by GLUT1 inhibition-induced starvation. This "valve-closing" starvation strategy provides a promising paradigm for the development of novel nanotherapeutics with amplified chemotherapy effect.