Mito-specific cascade amplifier sniping metabolism homeostasis for multimodal imaging-guided antitumor bioenergetic therapy  

作　　者：Jingjing Yang Yuanlin Zhang Maoquan Chu Jin Qian Jie Liu Manyu Wang Zhe Qiang Jie Ren 

机构地区：[1]Institute of Nano and Biopolymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China [2]Molecular Biomarkers Nano-Imaging Laboratory, Brigham and Women’s Hospital, and Department of Radiology, Harvard Medical School, Boston, MA, 02115, USA [3]Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 20092, China [4]118 College Dr, School of Polymer Science and Engineering, The University of Southern Mississippi, Hattiesburg, MS, 39406, USA

出　　处：《Nano Research》2024年第11期9908-9919,共12页纳米研究（英文版）

基　　金：financially supported by the Shanghai 2020 “Science and Technology Innovation Action Plan” Social Development Science and Technology Research Project(No.20dz1203600);the Fundamental Research Funds for the Central Universities,and the Open Funds for Characterization of Tongji University.

摘　　要：Nicotinamide adenine dinucleotide (NAD+/NADH) pools homeostasis is recognized as an Achilles’ Heel in tumor metabolism reprogramming. However, mitochondria can enable cancer cells to overcome NADH exhaustion by providing NAD+ precursors and/or intermediates, thus promoting their survival rate and potentially driving uncontrollable proliferation. Here, a synergistic intervention NAD+/NADH homeostasis and mitochondrial metabolism strategy with magnetic resonance imaging (MRI)/photoacoustic imaging (PAI) are developed to address grand challenge of metabolic reprogramming for antitumor bioenergetic therapy. A mitochondrial-targeted cascade amplification nanoplatform ([β-MQ]TRL), triggered by NAD(P)H: quinone oxidoreductase-1 (NQO1), can enable a continuous depletion of cytosol NADH until cell death. The end-product, hydrogen peroxide (H_(2)O_(2)), can be further catalytically converted to higher toxic ·OH in proximity to mitochondria based on [β-MQ]TRL mediated Fenton-like reaction, hijacking tumorigenic energy sources and leading to mitochondrial dysfunction. Additionally, the mild thermal ablation enabled by [β-MQ]TRL further amplifies this cascade reaction to effectively prevent tumor metastasis and recurrence. This synchronous intervention strategy with MRI/PAI establishes unprecedented efficiency in antitumor bioenergetic therapy in vivo, which shows excellent promise for clinical application.

关 键 词：metabolism programming nicotinamide adenine dinucleotide(NAD+/NADH)pools homeostasis disruption mitochondrial-targeting cascade therapy magnetic resonance imaging(MRI)/photoacoustic imaging(PAI) 

分 类 号：R730.5[医药卫生—肿瘤]