Atomic iron-engineered dual-modal nanozyme enhances tumortargeted chemodynamic/photothermal synergistic therapyOA
To address monotherapy limitations in oncology,synergistic strategies are urgently needed to circumvent drug resistance and achieve favorable therapeutic outcomes.The development of new nanoformulations has emerged as one of the most promising approaches to resolve these challenges.In this study,we engineered an iRGD peptide-functionalized Fe single-atom nanozyme(FeSAN@iRGD)that integrates dual therapeutic modalities.The FeSAN@iRGD demonstrates exceptional peroxidase-like catalytic activity and achieves a remarkable 29.5%photothermal conversion efficiency under 808 nm laser irradiation,enabling effective synergistic chemodynamic therapy(CDT)and photothermal therapy(PTT).Density functional theory calculations reveal that the atomically dispersed Fe-N_(4)active sites facilitate efficient catalytic conversion of endogenous H_(2)O_(2)into highly cytotoxic hydroxyl radicals in tumor microenvironment.The surface-conjugated iRGD peptide significantly enhances tumor-targeted accumulation.Both in vitro and in vivo evaluations confirm that the combined CDT/PTT approach synergistically enhances tumor cell apoptosis and suppresses tumor growth.Proteomic analysis comprehensively revealed reactive oxygen species(ROS)-mediated pathways including response to ROS,apoptosis,metabolic reprogramming,and cell cycle.This multifunctional nanozyme provides a promising paradigm for overcoming the therapeutic limitations of conventional cancer treatments through rational integration of catalytic nanomedicine and tumor-targeting strategies.
Cai-Shi Lin;Wenhao Shi;Yanfei Zhu;Weiheng Ma;Yongjian Ai;Jing Wang;Qionglin Liang;Meng-Qi He
State Key Laboratory of Respiratory Health and Multimorbidity,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,ChinaMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology,Department of Chemistry,Laboratory of Flexible Electronics Technology,Center for Synthetic and Systems Biology,Tsinghua University-Peking University Joint Centre for Life Sciences,Tsinghua University,Beijing 100084,ChinaState Key Laboratory of Respiratory Health and Multimorbidity,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,ChinaState Key Laboratory of Respiratory Health and Multimorbidity,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,ChinaMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology,Department of Chemistry,Laboratory of Flexible Electronics Technology,Center for Synthetic and Systems Biology,Tsinghua University-Peking University Joint Centre for Life Sciences,Tsinghua University,Beijing 100084,China MOE Key Laboratory of Precision Nutrition and Food Quality,Department of Nutrition and Health,China Agricultural University,Beijing 100193,ChinaState Key Laboratory of Respiratory Health and Multimorbidity,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,ChinaMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology,Department of Chemistry,Laboratory of Flexible Electronics Technology,Center for Synthetic and Systems Biology,Tsinghua University-Peking University Joint Centre for Life Sciences,Tsinghua University,Beijing 100084,ChinaState Key Laboratory of Respiratory Health and Multimorbidity,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,China
医药卫生
single-Fe-atom nanozymecombinatorial cancer therapyphotothermal activityperoxidase-like activitysynergistic therapy
《Nano Research》 2026 (5)
P.809-825,17
supported by the National Natural Science Foundation of China(Nos.22304099,82304442,and 82574366)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2024-I2M-3-013 and 2023-I2M-2-001)the National Key R&D Program of China(Nos.2023YFC3504401 and 2022YFA1103403)Beijing Natural Science Foundation(No.L256002)Beijing Outstanding Young Scientist Program(No.JWZQ20240101019)Young Elite Scientist Sponsorship Program of the Beijing Association for Science and Technology(Nos.BYESS2023166 and BYESS2024140)State Key Laboratory Special Fund(No.2060204)China Postdoctoral Science Foundation Funded Project(Nos.2023T160372,2022M711779,and BX20220160)。
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