Peiqi Zhao,1 Yali Fan,2 Ziyou Wang,2 Heyun Tang,2 Yu Tian,3 Yingying Zhang2 

1Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China; 2School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 3School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, People’s Republic of China

Correspondence: Yu Tian; Yingying Zhang, Email tianyu@stu.pku.edu.cn; zhangyy@xzhmu.edu.cn

Introduction: Tumor vaccines can activate tumor-specific immune responses to inhibit tumor growth, recurrence, and metastasis. However, the efficiency of antigen and adjuvants combined delivery to lymph nodes (LNs) is relatively low, leading to weak immune stimulation and tolerance. In this study, a tumor nanovaccine was constructed for the targeted dendritic cells (DCs)-mediated immunotherapy.
Methods: Ovalbumin (OVA) antigen was first loaded into manganese-doped mesoporous silica nanoparticles (MMSNs) and coated with bacterial cytoplasmic membrane (BM), which was further inserted with mannose to prepare OVA@MMSNs@BM-Man nanovaccines. In vitro and in vivo experiments were conducted to assess their properties and function of the synthesized nanovaccines.
Results: The nanovaccine can effectively target DCs in LNs by the combination of mannose with mannose receptor (CD205). BM serves as an immune adjuvant and co-delivers with OVA antigen, effectively improving antigen presentation efficiency. In an acidic environment, the Mn2+ produced by the degradation of MMSNs can not only serve as an MR imaging agent but also activate the cGAS-STING pathway, followed by the release of IFN-β. The activated DCs further activate the body’s cytotoxic T cells (CTLs), thereby exerting anti-tumor effects.
The conclusion: This study will provide a new idea for the construction of tumor nanovaccines.

Keywords: tumor nanovaccine, immunotherapy, cGAS-STING pathway, MR imaging