Abstract P1044: A Drug-Like Activity Of Polydopamine Nanoparticles Mediates Cardiomyocyte Bio-Modulation And Maturation

Abstract

Introduction: Bio-active nanomaterials are being extensively explored for various biomedical and tissue engineering applications. Polydopamine nanoparticles (PDA-NPs) is a self-assemble polymer derived from dopamine which has demonstrated anti-inflammatory potential by modulating immune cells. The use of PDA-NPs as bio-active nanomaterial for cardiac tissue repair/regeneration warrants further exploration. Hypothesis: We hypothesize that the polydopamine nanoparticles could modulate cardiomyocyte activity due to the presence of catechol moieties and may alter the gene expression and promote maturation of cardiomyocyte. Results: The PDA-NPs were fabricated by oxidative polymerization of dopamine monomers which resulted in formation of spherical nanoparticles. These nanoparticles were in the range of 100- 200 nm as evident from SEM and TEM imaging. The FTIR analysis of PDA-NPs revealed the characteristic peaks confirming the presence of quinone and catechol groups. These functional groups play important role in surface adhesion, thus imparting adhesive properties to PDA-NPs. The PDA-NPs were exposed to human iPSC-derived cardiomyocytes (HiPSC-CMs) and their real-time activity was monitored by using MEA. An instantaneous change in the beat period of cardiomyocytes was observed in a dose dependent manner. Moreover, a significant shortening in field potential duration was also seen, these finding suggest that the PDA-NPs stimulates the cardiomyocytes through catechol groups thereby exhibiting strong adrenergic effect. These finding demonstrates that PDA-NPs could significantly modulate the contractility of cardiomyocytes and could be used for enhancing cardiac contractility. Furthermore, prolonged incubation of PDA-NPs showed accumulation in the perinuclear region as revealed by fluorescence imaging. The influence of intracellular accumulation of PDA-NPs on gene expression was assessed by qRT-PCR. A significant increase in MYL2/MYL7 ratio, GJA5 and TNNI3 was noted, demonstrating the maturation of cardiomyocytes. Conclusion: Overall, the treatment of hiPSC-CMs cardiomyocytes with PDA-NPs shows dual response, primarily by modulating the contractility in a dose dependent manner and secondary by promoting maturation.