Inhalable cardiac targeting platelet biomimetic astragaloside IV derivative nanomedicine for the fibrotic heart repair

Myocardial fibrosis (MF) is a hallmark of adverse cardiac remodeling and a key driver of heart failure in cardiovascular diseases. Currently, the oral administrated drugs used for treating MF still have significant limitations, such as low efficiency of drug delivery to the heart and potential toxicity in long-term use. Inspired by the efficient cardiac delivery characteristics of inhaled drugs, this study developed a platelet-biomimetic nanomedicine PCL, consisted of carbonized Sophorae Flos -derived carbon dots loading with Astragaloside IV derivative (LS102) and followed by coated with the platelet membrane. As a result, compared with intravenous injection, inhaled PCL markedly improved the targeted delivery efficiency of the drug to the fibrotic myocardium, exhibiting an in vivo distribution profile characterized by pulmonary-to-systemic delivery followed by preferential accumulation in the heart. The long-term inhalation treatment regimen showed good efficacy without causing severe organ damage. Moreover, this study revealed that inhalation therapy mainly inhibited endothelial-mesenchymal transition, and reduced collagen deposition and myocardial damage, thus promoting fibrotic heart repair and cardiac function recovery post-MI. This study provides a novel idea for exploring targeted inhalation therapy for MI and proposes promising clinical strategies for the long-term management of MF.