Disease-Specific Determinants of Cardiovascular Nanomedicine: Mechanisms, Limitations, and Translational Opportunities

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, yet most therapies lack cardiovascular tissue- and cell-specificity, limiting efficacy and increasing off-target toxicity. Nanoparticle-based drug delivery systems offer opportunities to enhance myocardial targeting, improve pharmacokinetics, and enable controlled or stimuli-responsive release. However, despite extensive preclinical success, clinical translation of cardiovascular nanomedicine remains limited. A major gap is the insufficient integration of disease-specific cardiac biology into nanoparticle design. Here, we propose that the success of cardiovascular nanomedicine depends on integrating nanoparticle physicochemical properties and disease-specific microenvironmental conditions, including inflammation, vascular permeability, fibrosis, immune activation, and intracellular stress signaling. We provide a mechanistic and disease-contextual framework to guide nanoparticle design across major cardiovascular conditions, including myocardial infarction, heart failure, atherosclerosis, and doxorubicin-induced cardiotoxicity, while distinguishing cardiomyocyte-directed delivery from vascular-, immune-cell-, and stromal-targeted strategies. Here, we critically evaluate current targeting strategies and major translation barriers associated with cell-specific delivery, off-target organ accumulation, preclinical models, manufacturing and scalability, and long-term safety. This review shifts the paradigm from material-centric to biology-guided nanoparticle design and outlines actionable strategies to advance cardiovascular precision therapeutics toward clinical translation.

Abstract from PubMed (PMID 42992394). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.