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 provi...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.展开更多
采用发色底物法分别测定了47例老年急性脑血栓形成患者和45例健康者血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)活性。结果发现脑血栓组血浆 t-PA 活性明显低于对照组(P<0.01)。而 PAI 活性显著高于对照组(P<0.001)。提示老...采用发色底物法分别测定了47例老年急性脑血栓形成患者和45例健康者血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)活性。结果发现脑血栓组血浆 t-PA 活性明显低于对照组(P<0.01)。而 PAI 活性显著高于对照组(P<0.001)。提示老年脑血栓形成急性期体内纤溶系统功能调节失衡,可能为老年脑血栓形成的一个重要原因之一。展开更多
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.
文摘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.
文摘采用发色底物法分别测定了47例老年急性脑血栓形成患者和45例健康者血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)活性。结果发现脑血栓组血浆 t-PA 活性明显低于对照组(P<0.01)。而 PAI 活性显著高于对照组(P<0.001)。提示老年脑血栓形成急性期体内纤溶系统功能调节失衡,可能为老年脑血栓形成的一个重要原因之一。