Temperature-dependent cell death patterns induced by functionalized gold nanoparticle photothermal therapy in melanoma cells

Sci Rep. 2018 Jun 7;8(1):8720. doi: 10.1038/s41598-018-26978-1.

Abstract

Photothermal therapy (PTT) is a promising approach for cancer targeting therapy. However, the temperature-dependent killing of tumor cells in PTT remains unclear. In this study, we report necroptosis plays a role in the anti-tumor effects observed in gold nanorod (GNR)-mediated PTT in melanoma. We first synthesized gold nanorods with a targeting adaptor FA (GNRs-FA), which achieved high efficacy of targeted delivery to melanoma cells. We further demonstrated PTT, precipitated by GNRs-FA under the induction of near-infrared laser, was temperature-dependent. Furthermore, the photothermal killing of melanoma cells showed different patterns of cell death depending on varying temperature in PTT. In a lower temperature at 43 °C, the percentages of apoptosis, necroptosis and necrosis of tumor cells were 10.2%, 18.3%, and 17.6%, respectively, suggesting the cell killing is ineffective at lower temperatures. When the temperature increased to 49 °C, the cell death pattern switched to necrosis dominant (52.8%). Interestingly, when the PTT achieved a moderate temperature of 46 °C, necroptosis was significantly increased (35.1%). Additionally, GNRs-FA/PPT-mediated necroptosis was regulated by RIPK1 pathway. Taken together, this study is the first to demonstrate that temperature-dependent necroptosis is an important mechanism of inducing melanoma cell death in GNR-mediated PTT in addition to apoptosis and necrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Gold / chemistry
  • Gold / pharmacology*
  • Hot Temperature*
  • Hyperthermia, Induced*
  • Melanoma, Experimental* / metabolism
  • Melanoma, Experimental* / pathology
  • Melanoma, Experimental* / therapy
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use*
  • Mice
  • Necrosis
  • Phototherapy*

Substances

  • Gold