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Reshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide-Assembly-Based Nanosystem

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    Reshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide-Assembly-Based Nanosystem
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    • Jiayan Lang
      Jiayan Lang
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      Sino-Danish Center for Education and Research, Sino-Danish College of UCAS, Beijing 100190, China
      More by Jiayan Lang
    • Xiao Zhao
      Xiao Zhao
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      More by Xiao Zhao
    • Yingqiu Qi
      Yingqiu Qi
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      School of Basic Medical Sciences, Zhengzhou University, Henan 450001, China
      More by Yingqiu Qi
    • Yinlong Zhang
      Yinlong Zhang
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      More by Yinlong Zhang
    • Xuexiang Han
      Xuexiang Han
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      More by Xuexiang Han
      Orcidhttp://orcid.org/0000-0003-0011-5222
    • Yanping Ding
      Yanping Ding
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      More by Yanping Ding
    • Jiajing Guan
      Jiajing Guan
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      More by Jiajing Guan
    • Tianjiao Ji*
      Tianjiao Ji
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      *E-mail: [email protected]
      More by Tianjiao Ji
      Orcidhttp://orcid.org/0000-0002-4479-4821
    • Ying Zhao*
      Ying Zhao
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      *E-mail: [email protected]
      More by Ying Zhao
    • Guangjun Nie*
      Guangjun Nie
      CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
      Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
      *E-mail: [email protected]
      More by Guangjun Nie
      Orcidhttp://orcid.org/0000-0001-5040-9793
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    ACS Nano

    Cite this: ACS Nano 2019, 13, 11, 12357–12371
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    https://doi.org/10.1021/acsnano.9b04857
    Published September 23, 2019
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    Abstract

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    Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAFs) play an important role in prostate tumor metastasis by shaping the malignant tumor microenvironment. Herein, we constructed a CAF-targeting siRNA delivery system by loading the fibroblast activation protein-α (FAP-α) antibody onto the cell-penetrating peptide (CPP)-based nanoparticles, which specifically downregulated C–X–C motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation generated a series of changes through inactivating CAFs so that the malignant prostate tumor microenvironment was reshaped. The tumor cell invasion, migration, and tumor angiogenesis were significantly inhibited, which all contributed to the suppression of the metastasis of an orthotopic prostate tumor. This tumor microenvironment reshaping strategy via CAF targeting and inactivation provides an alternative approach for malignant prostate tumor metastasis inhibition.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.9b04857.

    • Additional experimental data such as DLS characterization, expression changes of cytokines, cytotoxicity, and blood clearance rate shown in Tables S1–S3 and Figure S1–S9 (PDF)

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    Cite this: ACS Nano 2019, 13, 11, 12357–12371
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