Yaping Zhang: Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, P.R. China. ORCID
Hongkun Xu: State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P.R. China.
Leying Jiang: State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P.R. China.
Zhaodi Liu: Department of Radiation Oncology, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, P.R. China.
Chenshan Lian: Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, P.R. China.
Xiaofeng Ding: Department of Radiation Oncology, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, P.R. China.
Chuan Wan: State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P.R. China.
Na Liu: State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P.R. China.
Yuena Wang: State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P.R. China.
Zhiqiang Yu: School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, P.R. China. ORCID
Lizhi Zhu: Department of Pharmacy, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), The First Affiliated Hospital of Shenzhen University, Shenzhen 518055, P.R. China.
Feng Yin: Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, P.R. China.
Zigang Li: Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, P.R. China. ORCID
Peptide-based neoantigen vaccines hold tremendous potential for personalized tumor immunotherapy. However, effective delivery and controllable release of antigen peptides remain major challenges in stimulating robust and sustained immune responses. Programmable DNA nanodevices provide accurate fixed positions for antigens, which are convenient for the calculation of clinical dosage, and hold great potential as precise carriers. Here, a peptide-nucleic acid conjugate was prepared, which was driven by a propargyl sulfonium-based efficient and reversible bio-orthogonal reaction under weakly alkaline conditions, and folded into regular DNA nanodevice vaccines. The well-defined nanoplatform not only exhibits outstanding stability in serum, satisfactory safety, and effective internalization by antigen-presenting cells (RAW264.7 and BMDCs) but also obviously enhances cytokine (TNF-α, IL-6, and IL-12) secretion for further immune response. , the nanovaccine cooperating with OVA model antigens and CpG adjuvants stimulated an antigen-specific CD8T cell response, significantly preventing the lung metastases of melanoma. In the B16-OVA tumor-bearing model, the growth inhibition rate of melanoma reached up to 50%. Similarly, the DNA nanodevice with neoantigen induced up to a maximum degree of complete MC-38 tumor regression in 80% of mice, possibly owing to antigen peptide reversible release driven by sulfonium and further cross-presentation. In brief, this study demonstrates that DNA nanodevices with sulfonium centers can provide a precise, biocompatible, and effective co-delivery vaccine platform for tumor immunotherapy and prevention.
