초록 |
Nanostructures such as nanosheets, and nanoballs have been studied for delivery of chemical anticancer drugs and oligonucleotides. Although numerous studies have been done, the translation to commercialized products has not been successful. We aimed to design nanosystems which can modulate the immune microenvironment of tumors. For immunotherapy, adjuvant-loaded nanoparticles were modified with immune checkpoint blockade. In tumor-bearing xenograft, the surface-modified nanostructures provided selective activation by cleavage of fibroblast-associated protein at tumor microenvironment, and greater antitumor effect than other comparison groups. Moreover, we designed an adjuvant-entrapped nanoparticle which can assemble with tumor antigens in situ for effective activation of immune cells. The systemic administration of adjuvant-entrapped nanoparticles with near infrared light irradiation increased the activity of immune cell infiltration to the tumor cells, and inhibited tumor growth. In another study, we used gene-editing technique for restructuring of tumor immune microenvironment. The delivery of plasmid DNA encoding Cas9 and TGF-specific sgRNA using lipid nanoparticles increased the infiltration of immune cells to the tumor microenvironments. Taken together, these studies provide potentials of modulating immune microenvironment of tumors for potentiated immunotherapy. |