Biomimetic inhalable nanovesicles for enhanced cardiac therapy of heart failure following myocardial infarction

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, and myocardial infarction (MI) frequently progresses to heart failure despite advances in contemporary therapies. A major barrier to the clinical translation of cardioprotective biologics is the lack of noninvasive, organ-targeted delivery systems suitable for repeated administration. Although inhalation is an attractive route for systemic delivery, strategies that efficiently direct inhaled nanocarriers from the lung to the injured heart remain limited. In a murine MI model, inhaled PPL showed greater accumulation in infarcted myocardium than unmodified liposomes after pulmonary administration. Repeated administration of IGF@PPL significantly improved cardiac function, attenuated adverse ventricular remodeling and fibrosis, and enhanced angiogenesis, without inducing detectable pulmonary or systemic toxicity. Collectively, these findings support the feasibility of pulmonary-to-systemic delivery followed by preferential cardiac accumulation and provides a broadly applicable framework for inhalable nanomedicine-based treatment of myocardial injury.