Photobiomodulation combined with photodynamic therapy using ruthenium phthalocyanine complexes in A375 melanoma cells: Effects of nitric oxide generation and ATP production

J Photochem Photobiol B. 2019 Sep:198:111564. doi: 10.1016/j.jphotobiol.2019.111564. Epub 2019 Jul 25.

Abstract

Light irradiation has been used in clinical therapy for several decades. In this context, photobiomodulation (PBM) modulates signaling pathways via ROS, ATP, Ca2+, while photodynamic therapy (PDT) generates reactive oxygen species by excitation of a photosensitizer. NO generation could be an important tool when combined with both kinds of light therapy. By using a metal-based compound, we found that PBM combined with PDT could be a beneficial cancer treatment option. We used two types of ruthenium compounds, ([Ru(Pc)], Pc = phthalocyanine) and trans-[Ru(NO)(NO2)(Pc)]. The UV-vis spectra of both complexes displayed a band in the 660 nm region. In the case of 0.5 μM trans-[Ru(NO)(NO2)(Pc)], light irradiation at the Q-band reduced the percentage of viable human melanoma (A375) cells to around 50% as compared to [Ru(Pc)]. We hypothesized that these results were due to a synergistic effect between singlet oxygen and nitric oxide. Similar experiments performed with PDT (660 nm) combined with PBM (850 nm) induced more photocytotoxicity using both [Ru(Pc)] and trans-[Ru(NO)(NO2)(Pc)]. This was interpreted as PBM increasing cell metabolism (ATP production) and the consequent higher uptake of the ruthenium phthalocyanine compounds and more efficient apoptosis. The use of metal-based photosensitizers combined with light therapy may represent an advance in the field of photodynamic therapy.

Keywords: Light irradiation therapy; Metal-based drug; Nitrosyl ruthenium-phthalocyanine complex; Photobiomodulation.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Coordination Complexes / therapeutic use
  • Humans
  • Light
  • Melanoma / drug therapy
  • Melanoma / metabolism
  • Melanoma / pathology
  • Nitric Oxide / metabolism*
  • Organometallic Compounds / chemistry*
  • Photochemotherapy
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Singlet Oxygen / metabolism

Substances

  • Coordination Complexes
  • Organometallic Compounds
  • Photosensitizing Agents
  • ruthenium phthalocyanine
  • Singlet Oxygen
  • Nitric Oxide
  • Adenosine Triphosphate