An Antibody-like Polymeric Nanoparticle Removes Intratumoral Galectin-1 to Enhance Antitumor T-Cell Responses in Cancer Immunotherapy

ACS Appl Mater Interfaces. 2021 May 19;13(19):22159-22168. doi: 10.1021/acsami.1c02116. Epub 2021 May 6.

Abstract

Antibodies have shown potential to deplete immunosuppressive factors in tumor tissues. However, intrinsic drawbacks, including time-consuming processes in preparation, high cost, and short half-life time, greatly restrict their applications. In this work, we report an antibody-like polymeric nanoparticle (APN) that is capable of specifically capturing and removing galectin-1 in tumor tissues, thereby enhancing the antitumor T-cell responses. The APN is composed of an albumin-polymer hybrid nanoparticle (core) and an acid-responsive PEG shell. The core of the APN contains multiple recognition units and Tuftsin peptides to capture target factors and activate macrophage-mediated phagocytosis, respectively. By employing galactose as recognition units, the APN facilitated the phagocytosis of galectin-1 in tumor tissues, thereby improving the antitumor responses of tumor-infiltrating T cells. Since the recognition units in the APN can be further replaced to capture and remove other peptides/proteins, the APN provides a feasible approach for the development of synthetic nanoformulations to regulate biological systems and treat diseases.

Keywords: antibody-like polymeric nanoparticle; cancer immunotherapy; galectin-1; macrophage; tumor microenvironment.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Galectin 1 / isolation & purification*
  • Humans
  • Immunotherapy / methods*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Phagocytosis
  • Polymers / chemistry*
  • RAW 264.7 Cells
  • Tumor Microenvironment / immunology

Substances

  • Galectin 1
  • Polymers