Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots

ACS Appl Mater Interfaces. 2024 Apr 17;16(15):18534-18550. doi: 10.1021/acsami.4c00853. Epub 2024 Apr 4.

Abstract

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.

Keywords: Fenton-like reaction; copper-doped carbon dots; immunogenic cell death; immunosuppression; oxygenation.

MeSH terms

  • Carbon / pharmacology
  • Cell Line, Tumor
  • Copper / chemistry
  • Humans
  • Hydrogen Peroxide / chemistry
  • Hypoxia
  • Immunogenic Cell Death
  • Nanoparticles* / chemistry
  • Neoplasms* / drug therapy
  • Oxygen / chemistry
  • Silicon Dioxide / pharmacology
  • Tumor Microenvironment

Substances

  • Silicon Dioxide
  • Copper
  • Carbon
  • Oxygen
  • Hydrogen Peroxide