Recombinant VAR2CSA malaria protein-targeted exosome-mediated DACT2 gene therapy for effective glioma treatment.

A good non-viral vector is the key to the success of gene delivery and therapy; hence, modified exosomes may overcome the physiological barrier in the delivery in vivo. This study aims to design a novel non-viral vector and verify its gene delivery function in vitro and in vivo for dapper homolog 2 (DACT2) genes. In this study, amphipathicity cationic exosomes with receptor targeted function and DACT2 gene loading function were constructed by exosomes, PEG, glycidyl hexadecyl dimethylammonium chloride, and recombinant VAR2CSA malaria protein (RVP) antibody. Characterizations of RVP antibody and PEG modified cationic lipid exosome (RVP-CL) nanocomplexes were evaluated by dynamic light scattering, atomic force microscopy, FTIR, and so on. The DNA condensation ability and stability were assessed by agarose gel electrophoresis. Cellular uptake efficiency and cytotoxicity in glioma cells were investigated. Furthermore, the tumor suppressive effect was evaluated in vitro and in vivo. The results indicated that RVP-CL had a uniform size of 100–200 nm and positive zeta potential. With high uptake efficiency, RVP-CL can rapidly target, recognize, and enter the glioma cell (KNS-42 and U118 mg) and release the gene. Moreover, RVP-CL/DACT2 can effectively inhibit the growth of glioma cells in vitro and in vivo. The modified cationic exosomes may offer a promising strategy for gene delivery in the treatment of RVP-positive gliomas or other tumors. [ABSTRACT FROM AUTHOR]