Enhanced Antitumor Immunity Using a Tumor Cell Lysate-Encapsulated CO2-Generating Liposomal Carrier System and Photothermal Irradiation.

Abstract

Dendritic cell (DC)-based cancer immunotherapies have been studied extensively. In cancer immunotherapy, the initial key step is the delivery of tumor-specific antigens, leading to the maturation and activation of DCs. To promote effective antigen delivery, liposome-based delivery systems for tumor-specific antigens have been investigated, and although promising, a triggered release of the antigen from the liposome is required to attain an optimum immune response. In this study, we developed CO2-bubble-generating thermosensitive liposomes (BG-TSLs) that encapsulate whole tumor cell lysates (TCLs). The release of the lysate from BG-TSLs can be triggered using near-infrared (NIR) irradiation. We also developed BG-TSLs able to encapsulate doxorubicin (DOX) for combination therapy. The DOX-BG-TSLs and TCL-BG-TSLs have a mean particle size of 114.17 ± 8.28 nm and 123.8 ± 10.2 nm and a surface charge of -22.56 ± 1.3 mV and -28.9 ± 0.8 mV, respectively. CO2 bubble generation within TCL-BG-TSLs and DOX-BG-TSLs by NIR irradiation led to the burst release of TCL or DOX. TCL release from TCL-BG-TSLs promoted dendritic cell maturation and activation, leading to the emergence of antigen-specific cytotoxic CD8+ T cells. The combination of TCL-BG-TSLs with DOX-BG-TSLs showed a significantly greater antitumor efficacy in B16F10 tumor-bearing mice compared to that seen in the control mice (P < 0.001). Taken together, our liposomal delivery system, combined with NIR irradiation, could enhance the therapeutic efficacy of cancer immunotherapies.