Ferric Hydroxide-Modified Upconversion Nanoparticles for 808 nm NIR-Triggered Synergetic Tumor Therapy with Hypoxia Modulation

ACS Appl Mater Interfaces. 2019 Jan 9;11(1):385-393. doi: 10.1021/acsami.8b18427. Epub 2018 Dec 28.

Abstract

The efficacy of dynamic therapy for solid tumors suffers daunting challenges induced by tumor hypoxia. Herein, we report a biocompatible nanosystem containing Fe(OH)3-modified upconversion nanoparticles (UCNPs) for promoting synergetic chemo- and photodynamic therapy with the modulation of tumor hypoxia. In this system, UCNPs convert 808 nm near-infrared excitation to visible photon energy, which stimulates chlorin-e6 photosensitizers to generate toxic reactive oxygen species (ROS) by consumption of dissolved oxygen in cancer cells. Importantly, we employ Fe(OH)3 compounds to enable continuous oxygen generation in cancer cells and, meanwhile, induce extra ROS formation through the Fenton-like reaction. The system consequently improves the tumor treatment efficacy in vitro and in vivo. This study puts forward a novel combinatorial therapeutic platform for tumor microenvironment modulation and enhanced cancer therapy.

Keywords: Fenton-like reaction; ferric hydroxide nanocolloid; photodynamic therapy; tumor hypoxia; upconversion nanoparticles.

MeSH terms

  • Animals
  • Cell Hypoxia / drug effects
  • Cell Line, Tumor
  • Chlorophyllides
  • Ferric Compounds* / chemistry
  • Ferric Compounds* / pharmacokinetics
  • Ferric Compounds* / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Photochemotherapy*
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacokinetics
  • Photosensitizing Agents* / pharmacology
  • Porphyrins* / chemistry
  • Porphyrins* / pharmacokinetics
  • Porphyrins* / pharmacology
  • Reactive Oxygen Species / metabolism
  • Tumor Microenvironment / drug effects

Substances

  • Chlorophyllides
  • Ferric Compounds
  • Photosensitizing Agents
  • Porphyrins
  • Reactive Oxygen Species
  • ferric hydroxide
  • phytochlorin