Abstract
ABSTRACT
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.