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Intelligent bioinspired nanovesicles for controllable immune microenvironment reprogramming of drug-resistant breast cancer treatment    

文献类型:期刊文献

中文题名:Intelligent bioinspired nanovesicles for controllable immune microenvironment reprogramming of drug-resistant breast cancer treatment

作者:Senyi Gong[1];Yu Liu[1];Jinzhao He[1];Mengdi Shang[2];Waleed Aldahmash[3];Juan Gallo[4];Kamran Ashraf[1];Saria Sajid[1];Muhammad Hammad Hussain[1];Mingwei Shen[1];Touseef Ur Rehman[1];Meijin Guo[1];Ali Mohsin[1]

机构:[1]State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China;[2]School of Life Sciences and Health Engineering,Jiangnan University,Wuxi 214122,China;[3]Zoology Department,College of Science,King Saud University,P.O.Box 2455,Riyadh 11451,Saudi Arabia;[4]International Iberian Nanotechnology Laboratory,Av.Mestre JoséVeiga s/n 4715-330 Braga,Portugal

年份:2026

卷号:19

期号:5

起止页码:876

中文期刊名:Nano Research

外文期刊名:纳米研究(英文版)

基金:supported by the National Foreign Expert Program of China(No.Y20240198);the National Natural Science Foundation of China(No.22578120);the Ongoing Research Funding Program(No.ORF-2026-1080),King Saud University,Riyadh,Saudi Arabia。

语种:英文

中文关键词:multidrug resistance;exosome;immunotherapy;macrophages;photothermal therapy

摘要:The immunosuppressive tumor microenvironment(TME)plays a critical role in the exacerbation of chemotherapy-induced multidrug resistance(MDR).To overcome MDR,a natural nanovesicle-based biomimetic nanosystem was created using low-frequency vibrational magnetic fields(VMF)and an 808 nm laser to help overcome drug resistance in tumors.This advanced platform integrates M1 macrophage-derived exosomes(M1-EXO)with magnetic nanoparticles,Ce6 labeled antisense oligonucleotides of heat shock protein 70(HSP-70)and doxorubicin.This approach enables a triple-modality synergistic therapy that integrates immunotherapy,gene therapy,and enhanced photothermal therapy(PTT).Specifically,M1-EXO effectively reprogram tumor-associated M2 macrophages(TAMs)toward the antitumor M1 phenotype,while Ce6-mediated photodynamic therapy(PDT)amplifies reactive oxygen species(ROS)-dependent M1 repolarization.Further,the nanovesicles target HSP70 to suppress heat shock protein expression,thereby overcoming the thermal resistance of tumor cells and enhancing PTT.Concurrently,nanovesicles'favorable magnetic responsiveness enables direct destruction of cancer cells under VMF exposure,which greatly contributed to immunogenic cell death(ICD)activation.Consequently,this synergistic strategy initiates antitumor immunity and activates cytotoxic T lymphocytes.Both in vitro and in vivo studies demonstrate that this biomimetic nanovesicle reduces the half-maximal inhibitory concentration(IC_(50))of doxorubicin-resistant breast cancer cells by 96-fold.In conclusion,this nanoplatform successfully tackles drug resistance by actively targeting pathways that activate the immune system,and promotes exosomes from human peripheral blood mononuclear cells for transplantation immunotherapy in the future.

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