Dual Gene-Loaded Near-Infrared AIEgen Nanoplatforms with Promoted Proliferation, Relieved Immunosuppression, and Tracking Capabilities for Cardiomyocyte Transplantation

Direct transplantation of cardiomyocytes (CMs) holds great potential to address the risk of arrhythmia and tumorigenesis associated with transplantation of pluripotent stem cell-derived CMs and the off-target issue related to in situ activation of cardiomyocyte proliferation using small molecules or genes for treating cardiovascular diseases (CVD). However, there remain several challenges associated with CM transplantation, such as limited proliferation capability, poor survival caused by immunosuppression from T lymphocytes, and a lack of information about CMs after in vivo administration. In this paper, we developed dual gene-loaded near-infrared AIEgen nanoplatforms with enhanced proliferation, relieved immunosuppression, and tracking capabilities for CM transplantation. First, we encapsulated a near-infrared emitting AIEgen (AIE810) with a customized amphiphilic polymer DSPE-PEI 2000 to afford AIE810@PEI nanoparticles (NPs). Then, we loaded the NPs with microRNA-302 for activating CM proliferation and siSOCS1 for attenuating immunosuppression from T lymphocytes by facilely mixing with nanoparticles to yield final nanoplatforms (i.e., AIE810@PEI-miR302-siSOCS1 NPFs). We demonstrated both in vitro and in vivo that CMs treated with the developed NPFs show significantly enhanced viability, proliferation, and in vivo survival as indicated by the MTT assay, Ki-67 staining, and in vivo subcutaneous CM tracking, respectively. The developed AIE810@PEI-miR302-siSOCS1 NPFs would be a powerful tool in advancing CM transplantation for treating CVD and optimizing the therapeutic route by in vivo CM tracking for accelerating clinical translation.