PEGylated doped- and undoped-TiO2 nanoparticles for photodynamic Therapy of cancers

Photodiagnosis Photodyn Ther. 2019 Sep:27:173-183. doi: 10.1016/j.pdpdt.2019.05.019. Epub 2019 May 25.

Abstract

Titanium dioxide has been widely known for its phototoxicity in the environmental context, but little is known for its use in the photodynamic therapy of cancers. Previous studides have shown the hazardous effects of undoped-titanium dioxide nanoparticles (undoped-TiO2 NPs) in the ecosystem; however, it remains to explore the effect of polyethylene glycol (PEG) conjugation and doping of metal and non-metal on the photodynamic activity of TiO2. Here we report the synthesis, characterizations, and applications of doped- and undoped-TiO2 NPs stabilized by PEG in the photodynamic therapy of cancers. Our results demonstrate that in vitro PEG-NPs significantly reduced the survival of human cervical cancer cells (HeLa) upon solar and ultraviolet (UV) radiations. We found that doping of the metal (cobalt) and non-metal (nitrogen) onto TiO2 nanocrystals enhanced the photoactivation of doped-TiO2 NPs in the visible/near infrared (Vis/NIR) region, but these nanocrystals were revealed by cytotoxicity assays to be less potent in killing cancer cells compared to PEGylated undoped-TiO2. The significant photodynamic effect was shown by PEGylated undoped-TiO2 synthesized through the sol-gel method with 75% killing of HeLa cells at 5.5 μg/mL concentrations in exposure to UV or sunlight radiations. In vitro cytotoxicity was measured by Sulforhodamine B (SRB) and 3-(4, 5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays after irradiations with IR, UV, and sunlight for 15-30 minutes (min). All the synthesized NPs were characterized by XRD, AFM, SEM, EDX and DRS chemical analysis. Taken together, our data demonstrate that water-soluble PEGylated TiO2 NPs maybe a good candidate for the photodynamic therapy of cervical cancer cells. Our data propose that the use of PEG surfactant can enhance the potency of already available photochemical therpeutic agents.

Keywords: Cancer; Nanoparticles; PEGylation; Photodynamic therapy; Phototoxicity; Titanium dioxide.

MeSH terms

  • Cell Survival / drug effects
  • Cobalt / chemistry
  • Drug Carriers / chemistry
  • Gold / chemistry
  • HeLa Cells
  • Humans
  • Metal Nanoparticles / chemistry*
  • Nitrogen / chemistry
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Polyethylene Glycols / chemistry*
  • Sunlight
  • Titanium / chemistry
  • Titanium / pharmacology*
  • Ultraviolet Rays

Substances

  • Drug Carriers
  • Photosensitizing Agents
  • titanium dioxide
  • Cobalt
  • Polyethylene Glycols
  • Gold
  • Titanium
  • Nitrogen