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In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy

  • Yue Yin
    Yue Yin
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
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  • , 
  • Xiaoyang Li
    Xiaoyang Li
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
    Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
    More by Xiaoyang Li
  • , 
  • Haixia Ma
    Haixia Ma
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
    More by Haixia Ma
  • , 
  • Jie Zhang
    Jie Zhang
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
    More by Jie Zhang
  • , 
  • Di Yu
    Di Yu
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden
    More by Di Yu
  • , 
  • Ruifang Zhao
    Ruifang Zhao
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
    More by Ruifang Zhao
  • , 
  • Shengji Yu
    Shengji Yu
    Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
    More by Shengji Yu
  • , 
  • Guangjun Nie*
    Guangjun Nie
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
    University of Chinese Academy of Sciences, Beijing 100049, China
    *(G.N.) Email: [email protected]
    More by Guangjun Nie
    Orcidhttp://orcid.org/0000-0001-5040-9793
  • , and 
  • Hai Wang*
    Hai Wang
    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
    University of Chinese Academy of Sciences, Beijing 100049, China
    *(H.W.) Email: [email protected]
    More by Hai Wang
    Orcidhttp://orcid.org/0000-0002-1292-998X
Cite this: Nano Lett. 2021, 21, 5, 2224–2231
Publication Date (Web):February 17, 2021
https://doi.org/10.1021/acs.nanolett.0c05039
Copyright © 2021 American Chemical Society
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    Abstract

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    Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumor-associated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8+ T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.nanolett.0c05039.

    • Experimental section; characterizations of GO, GLP, and GLP-RO Gel; transform capability, cellular uptake, GFP expression, and cytotoxicity of GLP-RO gel; activation of RAW264.7 and DC2.4 cells; gating strategy used for the flow cytometry analyses; body weight and H&E images of major organs for in vivo studies (PDF)

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