Mito-Specific Cascade Amplifier Sniping Metabolism Homeostasis for Multimodal Imaging-Guided Antitumor Bioenergetic Therapy
Document Type
Article
Publication Date
7-17-2024
School
Polymer Science and Engineering
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.
Publication Title
Nano Research
Recommended Citation
Yang, J.,
Zhang, Y.,
Chu, M.,
Qian, J.,
Liu, J.,
Wang, M.,
Qiang, Z.,
Ren, J.
(2024). Mito-Specific Cascade Amplifier Sniping Metabolism Homeostasis for Multimodal Imaging-Guided Antitumor Bioenergetic Therapy. Nano Research.
Available at: https://aquila.usm.edu/fac_pubs/21785