Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction: An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore function injured myocardium. Advanced approaches, such as stimulation cardiomyocyte (CM) proliferation promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution above-mentioned drawbacks. targeting cardiac tissue still represents challenge. Herein, MI-selective precision nanosystem developed, that relies on heart properties atrial natriuretic peptide (ANP) lin-TT1 peptide-mediated hitchhiking M2-like macrophages. The system based pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cells, ANP receptor-dependent interaction CMs. Moreover, treatment nanoparticles (NPs) loaded two pleiotropic cellular self-renewal promoting compounds, CHIR99021 SB203580, induces 4-fold increase in bromodeoxyuridine (BrdU) incorporation primary cardiomyocytes compared control. In vivo studies confirm macrophages by enhances ANP. addition, NP administration does not alter immunological profile blood spleen, showing short-term safety developed vivo. Overall, study results development peptide-guided for delivery therapeutic compounds infarcted heart.