Polyphenol-Nanoengineered Monocyte Biohybrids for Targeted Cardiac Repair and Immunomodulation

Myocardial infarction is one of the leading cause of cardiovascular death worldwide. Invasive interventional procedures and medications are applied to attenuate the attacks associated with ischemic heart disease by reestablishing blood flow and restoring oxygen supply. However, the overactivation of inflammatory responses and unsatisfactory drug delivery efficiency in the infarcted regions prohibit functional improvement. Here, a nanoengineered monocyte (MO)-based biohybrid system, referred to as CTAs @MOs, for the heart-targeted delivery of combinational therapeutic agents (CTAs) containing anti-inflammatory IL-10 and cardiomyogenic miR-19a to overcome the limitation of malperfusion within the infarcted myocardium through a polyphenol-mediated interfacial assembly, is reported. Systemic administration of CTAs@MOs bypasses extensive thoracotomy and intramyocardial administration risks, leading to infarcted heart-specific accumulation and sustained release of therapeutic agents, enabling immunomodulation of the proinflammatory microenvironment and promoting cardiomyocyte proliferation in sequence. Moreover, CTAs@MOs, which serve as a cellular biohybrid-based therapy, significantly improve cardiac function as evidenced by enhanced ejection fractions, increased fractional shortening, and diminished infarct sizes. This polyphenol nanoengineered biohybrid system represents a general and potent platform for the efficient treatment of cardiovascular disorders.