Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes.

Simple Summary: Heart disease is the leading cause of death worldwide. There is a need to develop a drug delivery system that can specifically target injured hearts and deliver therapeutic agents. Nanoparticles are a promising option for targeted drug delivery in both preclinical and clinical studies. However, the current nanoparticle-based drug delivery system does not have enough specificity in targeting the cardiac tissue. In this study, we have designed cardiac targeting peptides that focus on the molecules present in the cardiomyocyte membrane. Data from cell and animal studies have shown that when nanoparticles are conjugated with these peptides, their binding affinity to cardiomyocytes significantly improves. Therefore, we are developing a targeting system that can be utilized to deliver therapeutic compounds specifically to cardiomyocytes for the treatment of heart diseases. Background: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. Methods: We created three linear peptides, each consisting of 16–24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. Results: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. Conclusions: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues. [ABSTRACT FROM AUTHOR]