In Situ Programming of Nanovaccines for Lymph Node-Targeted Delivery and Cancer Immunotherapy

  • ACS Nano. 2022 Sep 27;16(9):15226-15236. doi: 10.1021/acsnano.2c06560.
Liangjie Jin  1 Dongmei Yang  2 Yonghong Song  3 Dongdong Li  1 Weijia Xu  2  4 Yueqiang Zhu  2  4 Cong-Fei Xu  2 Yang Lu  3 Xianzhu Yang  1  2  4  5
Affiliations
  • 1. Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, P. R. China.
  • 2. School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, Guangdong, P. R. China.
  • 3. Key Laboratory of Advanced Catalytic Materials and Reaction Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009, Anhui, P. R. China.
  • 4. National Engineering Research Center for Tissue Restoration and Reconstruction, and Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, Guangdong, P. R. China.
  • 5. Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology; Guangzhou 510006, P. R. China.
Abstract

In situ Cancer vaccines consisting of antigens and adjuvants are a promising Cancer treatment modality; however, the convenient manufacture of vaccines in vivo and their efficient delivery to lymph nodes (LNs) remains a major challenge. Herein, we outline a facile approach to simultaneously achieve the in situ programming of vaccines via two synergetic nanomedicines, Tu-NPFN and Ln-NPR848. Tu-NPFN (∼100 nm) generated a large number of antigens under an alternating magnetic field, and Ln-NPR848 (∼35 nm) encapsulating Adjuvant R848 captured a portion of generated antigens for the manufacture of nanovaccines in situ and LN-targeted delivery, which significantly promoted the uptake and maturation of dendritic cells to initiate potent Anticancer immune responses. Notably, combined with an anti-CTLA4 antibody (aCTLA-4), this therapy completely eradicated distant tumors in some mice and exerted a long-term immune memory effect on tumor metastasis. This study provides a generalizable strategy for in situ Cancer vaccination.

Keywords
cancer immunotherapy; immune response; in situ cancer vaccines; lymph nodes-targeted delivery; nanovaccines.
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