@article{Yang2024, 
author = {Jingjing Yang and Yuanlin Zhang and Maoquan Chu and Jin Qian and Jie Liu and Manyu Wang and Zhe Qiang and Jie Ren},
title = {Mito-specific cascade amplifier sniping metabolism homeostasis for multimodal imaging-guided antitumor bioenergetic therapy},
year = {2024},
journal = {Nano Research},
volume = {17},
number = {11},
pages = {9908-9919},
keywords = {metabolism programming, nicotinamide adenine dinucleotide (NAD+/NADH) pools homeostasis disruption, mitochondrial-targeting cascade therapy, magnetic resonance imaging (MRI)/photoacoustic imaging (PAI)},
url = {https://www.sciopen.com/article/10.1007/s12274-024-6892-y},
doi = {10.1007/s12274-024-6892-y},
abstract = {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 (H2O2), 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.}
}