Binary regulation of the tumor microenvironment by a pH-responsive reversible shielding nanoplatform for improved tumor chemo-immunotherapy. (15th January 2022)

• Record Type: Journal Article
• Authors: Sun, Xiaoyan; Zhang, Jiulong; Zhao, Xiufeng; Yang, Chunrong; Shi, Menghao; Zhang, Benzhuo; Hu, Haiyang; Qiao, Mingxi; Chen, Dawei; Zhao, Xiuli
• Is Part Of: Acta biomaterialia. Volume 138(2022)
• Page Start: 505
• Page End: 517
• Publication Date: 2022-01-15
• Subjects: phenylboronic acid PBA -- immunogenic cell death ICD -- calreticulin CRT -- adenosine-5′-triphosphate ATP -- high-mobility group box 1 HMGB1 -- platinum nanoparticle Pt NPs -- reactive oxygen sepsis ROS -- peroxidase POD -- oxidase OXD -- hydroxyl radical ·OH -- tumor associated macrophages TAMs -- interleukin-6 IL-6 -- epidermal growth factor EGF -- interleukin-10 IL-10 -- colony stimulating factor 1 receptor CSF-1R -- poly (lactic-co-glycolic acid PLGA -- tumor associated antigen TAAs -- enhanced permeability and retention effect EPR -- interferon-γ IFN-γ -- tumor necrosis factor-α TNF-α; Tumor microenvironment -- Cancer chemo-immunotherapy -- Tumor-associated macrophages -- Reversible ligand shielding -- pH-responsive; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2021.11.017
• Languages: English
• ISSNs: 1742-7061

Abstract

Abstract: The limited infiltration of specific T cells in an immunosuppressive microenvironment is a major challenge for cancer immunotherapy. Reversing tumor microenvironment and inducing an antitumor immune response are crucial for cancer therapy. Here, phenylboronic acid (PBA) derivative-stabilized ultrasmall platinum nanoparticles (PBA-Pt) and dextran-coated BLZ-945 nanoparticles (DNPs) were co-assembled through a pH-responsive borate ester bond to construct a versatile reversible shielding multifunctional nanoplatform (Pt@DNPs) for the first time. Pt@DNPs dissociated into two individual components, namely PBA-Pt and DNPs, in the tumor acid microenvironment. Both in vitro and in vivo studies revealed that Pt@DNPs induced immunogenic cell death (ICD) (through multimechanisms involving Pt Ⅱ release and a multienzyme catalytic process by PBA-Pt) and relieved immunosuppressive microenvironment (depletion of tumor-associated macrophages by BLZ-945), which led to tumor-associated antigen release, maturation of dendritic cells, and infiltration of cytotoxic T cells for efficient antitumor immune response against both primary tumor and pulmonary metastatic tumor nodules. Therefore, Pt@DNPs is a promising option for cancer chemo-immunotherapy. Statement of significance: A versatile reversible shielding multifunctional nanoplatform (Pt@DNPs) was engineered for the first time for combinational cancer chemo-immunotherapy. Multimechanisms involving induction of immunogenic cell death by PBA-Pt and sufficient TAM depletion by DNPs could efficiently relieve tumor immunosuppressive microenvironment and activate the antitumor immune response. The synergistic effect not only increased the infiltration of specific T cells in primary tumor, but it also induced a strong immune response against pulmonary metastatic nodules. Collectively, this nanoplatform may represent a promising strategy for combinational chemo-immunotherapy for cancers. Graphical abstract: Image, graphical abstract