Metabolic Reprogramming as a Therapeutic Node: Advances in Nanotechnology-based Cardiovascular Interventions

Cardiovascular diseases (CVDs) are increasingly recognized as diseases of high metabolic imbalance, where disruption in fatty acid oxidation, mitochondrial function, redox homeostasis, and cellular energetics can lead to heart failure. As traditional pharmacotherapies struggle to precisely modulate these metabolic pathways without systemic toxicity, nanotechnology has emerged as a transformative platform capable of targeted, controlled, and pathway-specific intervention. This narrative review synthesizes recent advances in metabolic reprogramming–targeted nanotherapies, highlighting how engineered nanoparticles enable precise modulation of cardiac metabolic pathways through delivery of siRNA, small molecules, and metabolic regulators, as well as mitochondrial-targeted and ROS-scavenging nanoplatforms. Preclinical studies demonstrate improved cardiac function, metabolic efficiency, and structural remodelling, underscoring the therapeutic potential of these approaches. However, clinical translation remains constrained by challenges in cardiomyocyte-specific targeting, biodistribution, long-term safety, and scalable formulation. Emerging strategies such as biomimetic nanoparticles, transcriptomic-guided targeting, and multifunctional nanoplatforms are discussed as promising directions for next-generation cardiovascular nanotherapeutics that address CVDs as fundamentally metabolic diseases.