Highly Efficient MicroRNA Delivery Using Functionalized Carbon Dots for Enhanced Conversion of Fibroblasts to Cardiomyocytes

Introduction: The reprogramming of induced cardiomyocytes (iCMs) is of particular significance in regenerative medicine; however, it remains a great challenge to fabricate an efficient and safe gene delivery system to induce reprogramming of iCMs for therapeutic applications in heart injury. Here, we report branched polyethyleneimine (BP) coated nitrogen-enriched carbon dots (BP-NCDs) as highly efficient nanocarriers loaded with microRNAs-combo (BP-NCDs/MC) for cardiac reprogramming. Methods: The BP-NCDs nanocarriers were prepared and characterized by several analytical techniques. Results: The BP-NCDs nanocarriers showed good microRNAs-combo binding affinity, negligible cytotoxicity, and long-term microRNAs expression. Importantly, BP-NCDs/MC nanocomplexes led to the efficient direct reprogramming of fibroblasts into iCMs without genomic integration and resulting in effective recovery of cardiac function after myocardial infarction (MI). Conclusion: This study offers a novel strategy to provide safe and effective microRNAsdelivery nanoplatforms based on carbon dots for promising cardiac regeneration and disease therapy.

Automated summary

This study successfully utilized branched polyethyleneimine (BP) coated nitrogen-enriched carbon dots (BP-NCDs) as carriers loaded with microRNAs-combo (BP-NCDs/MC), achieving direct reprogramming of fibroblasts into induced cardiomyocytes and effective recovery of cardiac function after myocardial infarction. This novel strategy provides a promising direction for cardiac regeneration and disease therapy through safe and effective microRNA delivery nanoplatforms based on carbon dots.