Cancer cell membrane-decorated hybrid liposomes for treating metastatic breast cancer based on enhanced cancer immunotherapy

Abstract

Purpose: Our goal was to increase the targetability of our nanoparticles to specific targets to increase their penetration into the tumor and to enhance immunotherapy with ketoconazole (KTZ), BMS-202, and indocyanine green (ICG)-induced photothermal therapy (PTT) for anticancer effects. Methods: We prepared liposomes through a thin film formation process in which hydrophobic drugs BMS-202 and KTZ were embedded in a lipid bilayer, and ICG was embedded inside the liposomes as a hydrophilic drug. In the process, the cell membranes of specific target cancer cells were fused to increase penetration and targeting. The resulting nanoparticles were evaluated in vitro and in vivo to confirm their anticancer effects. Results: Numerous experiments have demonstrated the properties of BMS-202/ICG/KTZ-loaded hybrid liposomes. The results of the in vitro/in vivo experiments confirmed successful enhancement of the targeting ability of the nanoparticles prepared by fusing with the cell membranes of specific cancer cells to increase their targetability and penetration. In addition, although the drug alone did not show significant cytotoxicity to 4T1 cancer cells by MTT assay, liposomes containing both KTZ and BMS-202 showed a significant effect on secondary tumor suppression in animal experiments compared to liposomes containing only a single drug, confirming the effectiveness of the enhanced immunotherapy. Conclusion: Our study showed that exosome inhibition and immune checkpoint blockade act synergistically in cancer immunotherapy.