The Research Of CAR-T Cell Membrane-coated Photothermal-responsive Nanoparticles In Targeted Therapy For Hepatocellular Carcinoma

Objective Hepatocellular carcinoma(HCC)is one of the most prevalent malignancies in the world.Apart from traditional surgical resection,radiotherapy,and chemotherapy,more recent techniques such as nano-photothermal therapy and biotherapy are gradually being adopted for the treatment of HCC.This project intends to contrast a novel nanoscale drug delivery systems by combining the advantages of nanotechnology with the targeting ability of chimeric antigen receptor T cells(CAR-T cells).Methods Based on cell membrane-coated nanoparticles and cell membrane-targeting modifications,a novel nanomaterial was prepared by coating CAR-T cell membranes specifically recognizing Glypican 3~+(GPC3~+)HCC cells onto mesoporous silica containing IR780 nanoparticles.Subsequently,the physical properties were characterized,and the in vitro and in vivo targeting abilities and photothermal antitumor properties of this nanoparticle were verified.Results CAR-T cells were constructed which could recognize GPC3 expressed on the cell surface of HCC cells.Then the isolated CAR-T cell membrane was successfully coated on the IR780 loaded mesoporous silica materials,as verified by transmission electron microscopy,then physical properties were characterized,.The superior targeting ability of CAR-T cell membrane coated nanoparticles compared to IR780loaded mesoporous silica nanoparticles was verified,both in vitro and in vivo.Conclusion This new nanomaterial exhibits photothermal antitumor abilities along with enhanced targeting abilities,suggesting a promising strategy for the treatment of HCC.