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

Author(s)

Negri, Laisa Bonafim ^[1] ; Martins, Tassia Joi ^[2] ; da Silva, Roberto Santana ^{[3, 2, 1]} ; Hamblin, Michael R. ^{[3, 4]}

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Ave Cafe S-N, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Ribeirao Preto, SP - Brazil

^[3] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 - USA

^[4] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 - USA

• Document type: Journal article
• Source: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY; v. 198, SEP 2019.
• Web of Science Citations: 1

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 mu M 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. (AU)

• FAPESP's process: 16/12707-0 - Cytotoxicity and photo-cytotoxicity of new ruthenium-phthalocyanines compounds as nitric oxide and oxygen singlet producers in cancer cell lines. an innovative purpose for metal based drug
• Grantee: Roberto Santana da Silva
• Support type: Regular Research Grants
• FAPESP's process: 15/03746-9 - Chemo-phototherapeutic process of phthalocyanine-ruthenium system and cisplatin: chemical and photobiological evaluation in aqueous solution and in drug delivery system
• Grantee: Laísa Bonafim Negri
• Support type: Scholarships in Brazil - Doctorate