Nanoparticle-Based Therapies for Myocardial Injury and Heart Failure: A Systematic Review and Translational Appraisal of Preclinical Evidence

Background: Heart failure remains a leading cause of morbidity and mortality, and current therapies rarely repair established myocardial damage. Nanoparticle-based interventions have been investigated across heterogeneous models of myocardial injury, remodeling, cardiomyopathy, and heart failure, but the distribution and translational maturity of this evidence remain unclear. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted from database inception to June 2024. Eligible reports were mapped according to disease model, experimental system, carrier-level nanoparticle platform, payload, route, comparator, outcomes, biodistribution, safety assessment, and translational characteristics. Reports of non-therapeutic nanoparticle exposure were retained in a separate contextual safety/toxicology stratum and were not included in the therapeutic evidence-density map. Risk of bias was evaluated using design-appropriate tools. Results: Of 2640 records screened, 157 independent studies met the criteria: 140 in the main therapeutic/platform evidence map and 17 in a separate contextual safety/toxicology stratum. Within the main corpus, polymeric systems were the largest platform class (n = 50), followed by inorganic/mineral (n = 35), biological/biomimetic (n = 24), lipid-based (n = 23), carbon-based (n = 5), and hybrid/multicomponent systems (n = 3). Evidence was concentrated in acute myocardial injury (n = 76), while direct same-agent comparisons, long-term safety assessment, repeated dosing, quantitative biodistribution, and clinically aligned heart-failure models remained limited. Conclusions: The field demonstrates substantial formulation diversity and biological activity, but translation is constrained by fragmented characterization, sparse comparative evidence, and incomplete assessment of biological fate and safety.