Hyaluronan-fullerene/AIEgen nanogel as CD44-targeted delivery of tirapazamine for synergistic photodynamic-hypoxia activated therapy

Nanotechnology. 2021 Aug 23;32(46). doi: 10.1088/1361-6528/ac18da.

Abstract

The therapeutic effect of oxygen-concentration-dependent photodynamic therapy (PDT) can be diminished in the hypoxic environment of solid tumours, the effective solution to this problem is utilising hypoxic-activated bioreduction therapy (BRT). In this research, a biocompatible HA-C60/TPENH2nanogel which can specifically bind to CD44 receptor was developed for highly efficient PDT-BRT synergistic therapy. The nanogel was degradable in acidic microenvironments of tumours and facilitated the release of biological reduction prodrug tirapazamine (TPZ). Importantly, HA-C60/TPENH2nanogel produced reactive oxygen species and consumed oxygen content in the cell to activate TPZ, leading to higher cytotoxicity than the free TPZ did. The intracellular observation of nanogel indicated that the HA-C60/TPENH2nanogel was self-fluorescence for cell imaging. This study applied PDT-BRT to design smart HA-based nanogel with targeted delivery, pH response, and AIEgen feature for efficient cancer therapy.

Keywords: AIEgen; hyaluronic acid; hypoxic-activated therapy; nanogel; photodynamic therapy.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Cell Line
  • Cell Line, Tumor
  • Fullerenes / chemistry*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Hyaluronic Acid / chemistry*
  • Hypoxia / drug therapy*
  • Hypoxia / metabolism
  • Nanogels / chemistry*
  • Nanoparticles / chemistry
  • Photochemotherapy / methods
  • Photosensitizing Agents / administration & dosage
  • Polyethylene Glycols / chemistry*
  • Polyethyleneimine / chemistry*
  • Prodrugs / administration & dosage
  • Reactive Oxygen Species / metabolism
  • Tirapazamine / administration & dosage*
  • Tirapazamine / chemistry*
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • CD44 protein, human
  • Fullerenes
  • Hyaluronan Receptors
  • Nanogels
  • Photosensitizing Agents
  • Prodrugs
  • Reactive Oxygen Species
  • polyethylene glycol polyethyleneimine nanogel
  • Tirapazamine
  • Polyethylene Glycols
  • Polyethyleneimine
  • Hyaluronic Acid