Small (Weinheim an der Bergstrasse, Germany) · 2026
Cardiomyocyte Membrane-Camouflaged Spinach Nano-Thylakoids Enhance Myocardial Energy Metabolism and Ameliorate Heart Failure.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Fan Haohui, Song Bei, Liu Chengyun, Zhong Peiyu, Zhou Quan, Zhao Xiaofang, Gao Guangyu, Zhang Xinyue, Guang Xueke, Yao Tianci, Liu Ting, Zhang Hao, Diao Xinqi, Lu Weilin
Аннотация
BACKGROUND: Energy deficiency and mitochondrial dysfunction are key features of heart failure (HF), while current therapies only indirectly improve cardiac metabolism. We developed a biomimetic photoactivatable nanoplatform, cardiomyocyte membrane-camouflaged photosynthetic nano-thylakoids (MM-NTU), to enhance myocardial bioenergetics.
METHODS AND RESULTS: Nano-thylakoids were isolated from spinach chloroplasts, downsized, and coated with cardiomyocyte membranes to improve cardiac association and retention. In transverse aortic constriction (TAC) rats, intramyocardial MM-NTU administration combined with red-light activation improved systolic function, reduced fibrosis, and attenuated ventricular remodeling. In angiotensin II-injured cardiomyocytes, MM-NTU stabilized mitochondrial membrane potential, increased ATP production, and suppressed hypertrophic and profibrotic markers. Multi-omics analyses revealed restoration of glucose-related metabolites and mitochondrial energy intermediates, reduced oxidative stress, and improved bioenergetic efficiency. MM-NTU also modulated AMPK-related signaling and altered Pck1 and Adipoq expression, consistent with enhanced glucose utilization. Biodistribution and histological analyses showed favorable biocompatibility without evident major-organ toxicity.
CONCLUSIONS: MM-NTU enhances ATP generation, glucose utilization, and mitochondrial energy metabolism, thereby improving myocardial bioenergetics and cardiac function under pressure overload.
METHODS AND RESULTS: Nano-thylakoids were isolated from spinach chloroplasts, downsized, and coated with cardiomyocyte membranes to improve cardiac association and retention. In transverse aortic constriction (TAC) rats, intramyocardial MM-NTU administration combined with red-light activation improved systolic function, reduced fibrosis, and attenuated ventricular remodeling. In angiotensin II-injured cardiomyocytes, MM-NTU stabilized mitochondrial membrane potential, increased ATP production, and suppressed hypertrophic and profibrotic markers. Multi-omics analyses revealed restoration of glucose-related metabolites and mitochondrial energy intermediates, reduced oxidative stress, and improved bioenergetic efficiency. MM-NTU also modulated AMPK-related signaling and altered Pck1 and Adipoq expression, consistent with enhanced glucose utilization. Biodistribution and histological analyses showed favorable biocompatibility without evident major-organ toxicity.
CONCLUSIONS: MM-NTU enhances ATP generation, glucose utilization, and mitochondrial energy metabolism, thereby improving myocardial bioenergetics and cardiac function under pressure overload.