A simple strategy for chemo-photothermal ablation of breast cancer cells by novel smart gold nanoparticles

Photodiagnosis Photodyn Ther. 2019 Dec:28:25-37. doi: 10.1016/j.pdpdt.2019.08.019. Epub 2019 Aug 24.

Abstract

Combined therapeutics dependent on the synergistic effect between photothermal therapy (PTT) and chemotherapy have been anticipated to be the next generation of cancer treatment. For this purpose, a novel gold hydrosol was synthesized by a one-pot approach using poly (2-(dimethylamino) ethyl methacrylate-co- N-isopropylacrylamide-co- 2-vinylpyridine) P(DMAEMA-co-NIPAAM-co-VP) terpolymers as a reducing and stabilizing agent. The synthesized gold hydrosol was recoated by a novel carboxylic acid rich poly (N-isopropyl acrylamide-co-maleic anhydride-graft-citric acid) (PNIPAAm-co-PMA-g-CA) copolymer. Then the gold nanoparticles conjugated with Doxorubicin (DOX) and served as a smart photo synthesizer for chemo/photothermal therapy of MCF-7 breast cancer cells. The synthesized nanoparticles had mono-dispersed spherical morphology with a diameter below 30 nm. Our results from cellular uptake indicated that around 100% of the particles were uptake by MCF-7 cells in the first 3 h of exposure time. The temperature of nanocomposites considerably went up to 45 °C with 10 min exposure to near-infrared irradiation. As a striking result, a single round of PTT combined with a sub-therapeutic dose of DOX revealed a synergistic effect with an ability of robust anti-tumor response up to 99.99% (sum of the population of apoptotic and necrotic cells) demonstrated by Annexin-V, cell cycle and DAPI staining techniques. In conclusion, Near-infrared-mediated photothermal conversion exhibited high effectiveness of a combinational chemo-thermotherapy to treat cancer cells.

Keywords: Apoptosis; Combination therapy; Doxorubicin; Photothermal effect; Smart gold hydrosol.

MeSH terms

  • Breast Neoplasms / therapy*
  • Cell Survival
  • Combined Modality Therapy
  • Doxorubicin / pharmacology*
  • Female
  • Gold / pharmacology*
  • Humans
  • Hyperthermia, Induced / methods*
  • MCF-7 Cells
  • Metal Nanoparticles
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / pharmacology*
  • Phototherapy / methods*

Substances

  • Photosensitizing Agents
  • Gold
  • Doxorubicin