Phototoxicity evaluation of tetra-cationic ruthenium-arene-phosphine porphyrins in ovarian tumor cells.
PEREIRA, George Bueno Santana; ROCHA, Josias da Silveira; MELLO, Marcos Vinicius Palmeira; TEIXEIRA, Tamara; MORAES, Carlos André Ferreira; SILVA, Nádija Natalice Paixão da; DUTRA, Jocely de Lucena; FORTALEZA, Dario Batista; PRESCILIO, Isabella Cristina; SANTIAGO, Pedro Henrique de Oliveira; ARAUJO NETO, João Honorato de; COMINETTI, Marcia Regina; ELLENA, Javier; BATISTA, Alzir Azevedo; ROCHA, Fillipe Vieira.
PEREIRA, George Bueno Santana; ROCHA, Josias da Silveira; MELLO, Marcos Vinicius Palmeira; TEIXEIRA, Tamara; MORAES, Carlos André Ferreira; SILVA, Nádija Natalice Paixão da; DUTRA, Jocely de Lucena; FORTALEZA, Dario Batista; PRESCILIO, Isabella Cristina; SANTIAGO, Pedro Henrique de Oliveira; ARAUJO NETO, João Honorato de; COMINETTI, Marcia Regina; ELLENA, Javier; BATISTA, Alzir Azevedo; ROCHA, Fillipe Vieira.
Abstract: Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment, enabling selective cytotoxicity through light-activated photosensitizers. In this work, four tetra-cationic porphyrins and their zinc(II) metalloporphyrin analogues, each coordinated to four peripheral ruthenium(II) arene-phosphine units, were investigated as a new class of compounds (PRAP: Porphyrin-Ruthenium-Arene-Phosphine). The compounds were fully characterized by NMR spectroscopy (1H, 31P, COSY), UV-vis and fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, elemental analysis, and molar conductivity. No significant cytotoxicity toward MRC-5 cells was observed below 25 µM. In contrast, strong phototoxic activity was detected in A2780 ovarian cancer cells following irradiation (415 nm). The free-base porphyrins exhibited higher photodynamic activity (IC50 = 0.06 ± 0.01 µM) than their zinc(II) analogues (IC50 = 0.36 ± 0.08 µM). Among the compounds, H2P displayed the highest phototoxicity index. Morphological analyses revealed pronounced membrane and nuclear alterations consistent with oxidative stress-induced damage. These findings are supported by ROS generation, apoptosis-related features, and DNA photocleavage activity. Furthermore, photodynamic treatment inhibited spheroid growth in a 3D tumor model, particularly affecting the proliferative outer regions. Overall, PRAP compounds represent a promising platform for developing new photosensitizers for PDT.
@article={003307458,author = {PEREIRA, George Bueno Santana; ROCHA, Josias da Silveira; MELLO, Marcos Vinicius Palmeira; TEIXEIRA, Tamara; MORAES, Carlos André Ferreira; SILVA, Nádija Natalice Paixão da; DUTRA, Jocely de Lucena; FORTALEZA, Dario Batista; PRESCILIO, Isabella Cristina; SANTIAGO, Pedro Henrique de Oliveira; ARAUJO NETO, João Honorato de; COMINETTI, Marcia Regina; ELLENA, Javier; BATISTA, Alzir Azevedo; ROCHA, Fillipe Vieira.},title={Phototoxicity evaluation of tetra-cationic ruthenium-arene-phosphine porphyrins in ovarian tumor cells},journal={Biomaterials Advances},note={v. 187, p. 214953-1-214953-14 + supplementary data},year={2026}}