Cardiac stromal cell/platelet-inspired nanoparticles for targeted heart repair
Statement of Purpose: The development of stem cell-derived biomimetics as therapeutic biologics has the potential to revolutionize cardiovascular regenerative medicine.1 Here, we report on developing a cardiac stromal cell/platelet-inspired nanoparticle (SPIN) that has a cardiac stromal cell (CSC) core and a CSC-platelet hybrid membrane shell. The CSC core consists of therapeutic CSC-secreted secretome encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticle for sustained factor release to inhibit the upregulation of inflammatory cytokines (e.g., IL-1 and TNF-α) associated with myocardial ischemia/reperfusion (I/R) injury and encourage targeted repair of the injured heart. As shown in Fig. 1, CSC-platelet hybrid membranes (1:1 protein weight ratio) are fused with the PLGA nanoparticle encasing the CSC secretome to form the CSC-platelet hybrid membrane-coated nanoparticle (SPIN). For comparison, the nanoparticle coated with only CSC membrane (S-NP) and that with only platelet membrane (P-NP) are prepared in a similar fashion. The dual-membrane-coating is expected to combine the functions of two different cell types to both enhance the targetability to cardiovascular cells and trigger the regenerative beta 1 integrin signaling through contact with the injured host cardiomyocytes.2 We test the therapeutic potency of SPINs for the treatment of myocardial I/R injury in immunocompetent rats.
