Nanovaccine of tumor-derived antigenic microparticles for enhancing effect of arsenic trioxide in cancer immunotherapy

Arsenic trioxide (ATO) is highly effective for acute promyelocytic leukemia but has limited potency in solid tumors. Mitigating the systemic toxicity of ATO while enhancing its efficacy in treating solid tumors through the combination of ATO and immunotherapy remains a formidable challenge. In this study, we designed a cancer nanovaccine (MANs-CpG@T-MPs) consisting of ATO and CpG-loaded amino-modified mesoporous silica (MANs-CpG) coated with tumor-derived antigenic microparticles (T-MPs). MANs-CpG@T-MPs exhibited a homologous targeting ability, successfully delivering ATO to tumor tissue and eliciting an effective immunogenic cell death (ICD) response to improve the immunogenicity of the tumor. Furthermore, MANs-CpG@T-MPs comprised tumor antigens, endogenous danger signals, and additional CpG, activating dendritic cells and promoting antigen presentation by dendritic cells (DCs). Consequently, this triggered immune responses from antigen-specific T cell. The in vivo study suggested that MANs-CpG@T-MPs exhibited strong prophylactic and therapeutic efficacy in BALB/c mice with H22 tumors. Notably, the nanovaccine induced an ICD effect that activated the immunogenically "cold" tumor microenvironment into a "hot" one, displaying specific antitumor effects on H22 tumor-bearing mice with remarkable infiltration of effector immune cells. Our study presents an encouraging approach to improve chemotherapeutic outcomes utilizing targeted nanovaccine to boost anti-tumor immune responses.