Immune Modulator and Low-Temperature PTT-Induced Synergistic Immunotherapy for Cancer Treatment
Yue Duan, Han Yang, Junxiao Gao, Daohe Wei, Yue Zhang, Jian Wang, Xinhui Zhang, Jinchao Zhang, Kun Ge, Xiaoli Wu, Jin Chang
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.