Metal-Free Nanocomposites with Endogenous Labile Iron Pool Disturbing Capacity for Tumor Therapy through Synergetic Stock Depletion and Supply Blockage Strategy

作者全名："Zhao, Sheng; Chen, Ziqun; Wang, Jingjing; Chen, Chunmei; Ouyang, Yi; Wu, Mengyuan; Zhang, Qun; Cao, Yang; Liu, Hui"

作者地址："[Zhao, Sheng; Chen, Chunmei; Ouyang, Yi; Wu, Mengyuan; Liu, Hui] Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China; [Zhao, Sheng] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China; [Chen, Ziqun; Cao, Yang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Wang, Jingjing] Peking Univ, Sch Mat Sci & Engn, Beijing Key Lab Magnetoelect Mat & Devices BKL MMD, Beijing 100871, Peoples R China; [Zhang, Qun; Liu, Hui] Southern Med Univ, Guangdong Prov Key Lab Bone & Joint Degenerat Dis, Off Clin Trial Drug, Affiliated Hosp 3, Guangzhou 510630, Peoples R China"

通信作者："Liu, H (通讯作者)，Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China.; Cao, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.; Zhang, Q; Liu, H (通讯作者)，Southern Med Univ, Guangdong Prov Key Lab Bone & Joint Degenerat Dis, Off Clin Trial Drug, Affiliated Hosp 3, Guangzhou 510630, Peoples R China."

来源：ACS MATERIALS LETTERS

ESI学科分类：　

WOS号：WOS:001161293200001

JCR分区：Q1

影响因子：9.6

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Metal iron plays exceedingly important roles in maintaining normal biological activities and is stored as an intracellular labile iron pool (LIP). Disturbing LIP balance to disorganize physiological reactions holds great promise in tumor therapy yet is still lacking exploration. Herein, a novel synergetic strategy was designed for tumor therapy with high efficacy and biocompatibility, which was realized through the metal-free poly(lactic-co-glycolic acid) (PLGA)-ethylenediaminetetraacetic acid (EDTA)-ebselen (EBS) nanocomposites. After degradation, EDTA chelates Fe2+ to deplete intracellular LIP, and EBS inactivates DMT1 protein to inhibit iron supplementation from extracellular regions. This LIP destruction causes the downregulation of iron-sulfur cluster levels, which compromises mitochondrial energy metabolism and arrests the cell cycle. Effective tumor elimination is achieved under PLGA-EDTA-EBS treatment with negligible side effects. This work presents an effective formulation for tumor therapy through a synergetic stock depletion and supply blockage strategy, thereby providing essential implications for the design of tumor therapeutic methods with minimal biosafety issues."

基金机构："Basic and Applied Basic Research Project of Guangzhou Basic Research Program [CSTB2022NSCQ-MSX0120]; Natural Science Foundation of Chongqing [202201011600]; Senior Medical Talents Program of Chongqing for Young and Middle-aged, and the Basic and Applied Basic Research Project of Guangzhou Basic Research Program"

基金资助正文："This research was funded by the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0120), the Senior Medical Talents Program of Chongqing for Young and Middle-aged, and the Basic and Applied Basic Research Project of Guangzhou Basic Research Program (202201011600)."