Immune Modulator and Low-Temperature PTT-Induced Synergistic Immunotherapy for Cancer Treatment

Abstract

Immunotherapy has shown great potential in cancer therapeutics but has limitations of the insufficient activation of dendritic cells (DCs) and immune-suppressive microenvironment. To overcome these obstacles, a cascade synergistic immunotherapy nanosystem (denoted as CpG@PDA-FA) was designed to elevate anticancer immune response. The combination nanosystem including a photothermal agent polydopamine (PDA) and immunomodulator CpG oligodeoxynucleotides (CpG ODNs). On the one hand, polydopamine (PDA) acts as a photothermal agent to induce low-temperature PTT. It leads to immunogenic cell death (ICD), a programmed cell death pathway, which can activate DCs and enhance the antitumor immune response of T cells. On the other hand, CpG ODNs further promote maturation and migration of DCs as well as ameliorates the immunosuppression microenvironment of the tumor (TME). This paper focuses on a cancer synergistic treatment of ICD-induced immunotherapy by low-temperature PTT and ameliorates TME by immunomodulator CpG ODNs. We proved that CpG@PDA-FA NPs realized a remarkable synergistic treatment effect compared with respective single PTT or CpG therapy in the maturation of DCs and activation of T cells. In addition, CpG@PDA-FA NPs also reduced myeloid-derived suppressor cells and regulatory T cells to relieve immunosuppression. Hence, CpG@PDA-FA NPs provide a bidirectional immunotherapy strategy for tumor inhibition and highlight the cascade effects of low-temperature PTT and immunotherapy.