Powerful Anticolon Tumor Effect of Targeted Gene Immunotherapy Using Folate-Modified Nanoparticle Delivery of CCL19 To Activate the Immune System

Targeted gene delivery systems have recently shown potential clinical benefits in cancer treatment. Recently, the immunologic therapies application in cancer therapy also showed a continuously increase. CCL19 has shown its great potential as a candidate immunomodulator for colon cancer therapy by increasing the possibility of interaction among dendritic cells, T and B cells in secondary lymphatic tissue, thus regulating the primary (or secondary) adaptive immune responses. In this work, a folic acid modified targeted gene-delivery system consisting of DOTAP, MPEG-PLA, and Fa-PEG-PLA (F-DMA) was developed successfully through a self-assembly approach. We proved that CCL19 expression was much higher in cancer cells after transfection with F-DMA/CCL19 than after transfection with DMA/CCL19. The supernatant from cancer cells transfected with both F-DMA/CCL19 and DMA/CCL19 stimulated the activation and cytotoxicity of T lymphocytes, the maturation of DCs, and the polarization of macrophages in vitro. Moreover,...