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In Situ Manipulation of Dendritic Cells by an Autophagy-Regulative Nanoactivator Enables Effective Cancer Immunotherapy

  • Yi Wang
    Yi Wang
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
    More by Yi Wang
    Orcidhttp://orcid.org/0000-0003-3077-2899
  • , 
  • Yao-Xin Lin
    Yao-Xin Lin
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
    More by Yao-Xin Lin
  • , 
  • Jie Wang
    Jie Wang
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
    More by Jie Wang
  • , 
  • Sheng-Lin Qiao
    Sheng-Lin Qiao
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
    More by Sheng-Lin Qiao
    Orcidhttp://orcid.org/0000-0001-5006-5257
  • , 
  • Yu-Ying Liu
    Yu-Ying Liu
    National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, P.R. China
    More by Yu-Ying Liu
  • , 
  • Wen-Qian Dong
    Wen-Qian Dong
    National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, P.R. China
    More by Wen-Qian Dong
  • , 
  • Junqing Wang
    Junqing Wang
    Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
    More by Junqing Wang
  • , 
  • Hong-Wei An
    Hong-Wei An
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100149, P.R. China
    More by Hong-Wei An
  • , 
  • Chao Yang
    Chao Yang
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    More by Chao Yang
  • , 
  • Muhetaerjiang Mamuti
    Muhetaerjiang Mamuti
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
    More by Muhetaerjiang Mamuti
  • , 
  • Lei Wang
    Lei Wang
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    More by Lei Wang
  • , 
  • Bo Huang
    Bo Huang
    National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, P.R. China
    More by Bo Huang
  • , and 
  • Hao Wang*
    Hao Wang
    CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, P.R. China
    Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
    *E-mail: [email protected]
    More by Hao Wang
    Orcidhttp://orcid.org/0000-0002-1961-0787
Cite this: ACS Nano 2019, 13, 7, 7568–7577
Publication Date (Web):July 1, 2019
https://doi.org/10.1021/acsnano.9b00143
Copyright © 2019 American Chemical Society
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    Abstract

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    Cellular immunotherapeutics aim to employ immune cells as anticancer agents. Ex vivo engineering of dendritic cells (DCs), the initial role of an immune response, benefits tumor elimination by boosting specific antitumor responses. However, directly activating DCs in vivo is less efficient and therefore quite challenging. Here, we designed a nanoactivator that manufactures DCs through autophagy upregulating in vivo directly, which lead to a high-efficiency antigen presention of DCs and antigen-specific T cells generation. The nanoactivator significantly enhances tumor antigen cross-presentation and subsequent T cell priming. Consequently, in vivo experiments show that the nanoactivators successfully reduce tumor growth and prolong murine survival. Taken together, these results indicate in situ DCs manipulation by autophagy induction is a promising strategy for antigen presentation enhancement and tumor elimination.

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.9b00143.

    • Data file S1: The MS-ESI spectra of B peptide (TIF)

    • Data file S2: The HPLC spectra of B peptide (TIF)

    • Data file S3: The MS-ESI spectra of OVA peptide (TIF)

    • Data file S4: The HPLC spectra of OVA peptide (TIF)

    • Data file S5: The MS-ESI spectra of B(S) peptide (TIF)

    • Data file S6: The HPLC spectra of B(S) peptide (TIF)

    • Materials, methods of transfection, RNA extraction and laser scanning confocal microscopy imaging, characterization of peptide and copolymers, and toxicity assessment of nanoactivators in vitro and in vivo (PDF)

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