An Ion-Enhanced Oncolytic Virus-Like Nanoparticle for Tumor Immunotherapy

Angew Chem Int Ed Engl. 2022 Nov 7;61(45):e202210487. doi: 10.1002/anie.202210487. Epub 2022 Oct 12.

Abstract

T lymphocytes (T cells) are essential for tumor immunotherapy. However, the insufficient number of activated T cells greatly limits the efficacy of tumor immunotherapy. Herein, we proposed an oncolytic virus-mimicking strategy to enhance T cell recruitment and activation for tumor treatment. We constructed an oncolytic virus-like nanoplatform (PolyIC@ZIF-8) that was degraded in the acidic tumor environment to release PolyIC and Zn2+ . The released PolyIC exhibited an oncolytic virus-like function that induced tumor cell apoptosis and promoted T cell recruitment and activation through a tumor antigen-dependent manner. More importantly, the released Zn2+ not only enhanced T cell recruitment by inducing CXCL9/10/11 expression but also promoted T cell activation to increase interferon-γ (INF-γ) expression by inducing the phosphorylation of ZAP-70 via a tumor antigen-independent manner. This Zn2+ -enhanced oncolytic virus-mimicking strategy provides a new approach for tumor immunotherapy.

Keywords: Ion; Oncolytic Virus-Like; T Cell Activation; T Cell Recruitment; Tumor Immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Cell Line, Tumor
  • Humans
  • Immunotherapy
  • Nanoparticles*
  • Neoplasms* / therapy
  • Oncolytic Virotherapy*
  • Oncolytic Viruses* / metabolism

Substances

  • Antigens, Neoplasm