Cardiac-homing peptide-targeted colchicine-based drugstores with inhibiting inflammatory response for myocardial infarction improvement.

One of the primary challenges in addressing cardiac injury is the limited cardiac specificity of therapeutic drugs. Lipid nanoparticles (LNPs) are a relatively novel class of delivery vehicles used for administering RNA and various drugs. A major challenge in the treatment of cardiac injury remains the poor cardiac specificity of most therapeutic agents. Despite their promise as a relatively novel delivery platform for RNA and other payloads, LNPs do not adequately overcome this limitation. Nevertheless, these LNPs exhibited preferential accumulation in the liver rather than the heart. To address this off-target biodistribution and enhance delivery efficiency to cardiac tissue, surface functionalization with cardiac-homing peptides (CHP) was performed. In this study, the CHP-functionalized LNP loaded with colchicine (termed as CCP) was developed as a targeted therapeutic platform for myocardial repair. This novel drug delivery system successfully localizes to the ischemic myocardium and precisely releases CCP to hypoxic, mildly acidic cardiomyocytes. In conclusion, CCP presents a promising platform for the sustained and localized delivery of drugs to the heart, thereby enhancing the therapeutic efficacy for cardiovascular diseases.