Multifunctional Nanoplatform for Synergistic Cancer Therapy via Enhanced Immunogenic Cell Death and Immune Modulation

The development of treatments is highly demanded as cancer continues to rank among the serious threats to human health. Herein, we developed a multifunctional nanoplatform, ZnO2@PtMn@Tir@HA (denoted as ZPMTH), to facilitate the activation of immunogenic cell death and immune responses for tumor therapy. The ZPMTH acted as nanozyme to drive cascade reactions to produce abundant intratumoral reactive oxygen species including (•OH) and 1O2 at the tumor region, resulting in the death of tumor cells. The release of damage-associated molecular patterns accompanied by cancer cells apoptosis could stimulate effective immunogenic cell death (ICD) and reinforce the tumor immunogenicity. Simultaneously, the presence of Mn2+/Zn2+ would facilitate activation of cGAS-STING signaling pathway and arouse robust immunity. Additionally, the drug Tirabrutinib (Tir) could suppress activity of Bruton’s tyrosine kinase (BTK) and alleviate the immunosuppressive tumor microenvironment. Further study revealed that the ZPMTH was qualified in promoting the maturation of dendritic cells (DCs). The in vitro and in vivo investigation verified that the ZPMTH could restrain the proliferation of primary and contralateral rechallenge tumor model with satisfactory effectiveness. Therefore, ZPMTH provided a promising approach for introducing ICD nanoinducer into antitumor immunotherapy for synergistic cancer therapy.