Mesoporous Silica Nanoparticles Doped with Gold Nanoparticles for Combined Cancer Immunotherapy and Photothermal Therapy.

Abstract

Cancer immunotherapy is a treatment that utilizes the host immune system to fight against cancer. Inducing a cancer antigen-specific adaptive immune response is key in cancer immunotherapy. Although diverse immune cells including dendritic cells (DCs) and T cells infiltrate a tumor, the activation of such immune cells is inhibited, owing to an immunosuppressive tumor microenvironment. In this study, we propose mesoporous silica nanoparticles (XL-MSNs) decorated with gold nanoparticles (Au@XL-MSNs) for the delivery of a high amount of CpG-ODNs to the tumor site to activate DCs infiltrated within the tumor for the induction of an antigen-specific adaptive immune response. During an in vitro test, CpG-ODNs delivered using Au@XL-MSNs were shown to be more effectively internalized by bone-marrow-derived dendritic cells (BMDCs), resulting in an enhanced expression of costimulatory molecules and an increased secretion of pro-inflammatory cytokines compared to soluble CpG-ODNs. Furthermore, an in vivo test demonstrated a more significant tumor growth inhibition and an enhanced survival rate result from the intratumoral injection of Au@XL-MSN-CpG compared to that treated using soluble CpG-ODNs. Furthermore, through the induction of a photothermal effect based on the assembled AuNPs on XL-MSNs, an enhancement of the cancer immunotherapy was achieved by generating a cancer antigen at the tumor site, which can be processed by tumor-infiltrated DCs. These findings suggest that our approach can be applied as a synergistic platform for efficient cancer immunotherapy, enabling a delivery of immunostimulating signals as well as in situ antigen generation through a photothermal effect.