Cytotoxicity of structurally-modified chlorins aimed for photodynamic therapy applications

Autor(es)

Linares, Irwin A. P. ^[1] ; Martinelli, Leticia P. ^[2] ; Moritz, Milene N. O. ^[3] ; Selistre-de-Araujo, Heloisa S. ^[3] ; de Oliveira, Kleber T. ^[4] ; Perussi, Janice Rodrigues ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, Ave Trabalhador Sao Carlense 400, Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil

^[3] Univ Fed Sao Carlos, Dept Ciencias Fisiol, Sao Carlos, SP - Brazil

^[4] Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY; v. 425, MAR 1 2022.
• Citações Web of Science: 0

Resumo

Photodynamic Therapy (PDT) is a promising treatment for various types of cancer and other non-oncological diseases. This technique uses a photosensitizer (PS) that generates reactive oxygen species (ROS), which lead cells to death in the presence of light and molecular oxygen. In this study, we evaluated the photoactivity of four chlorins that presented an L-type structure conformation (6a, 6b, 8a, and 8b) in two tumoral (HEp-2 and HeLa) and one non-tumoral (Vero) cell line under PDT conditions. Intracellular accumulation and subcellular localization were determined by confocal microscopy, showing that these chlorins exhibited an excellent (120 min) internalization through the plasmatic membrane with mitochondria and lysosome localization. The chlorins 6a-b were two and three-fold more selective than the chlorins 8a-b to HEp-2 and HeLa compared to Vero at 3 and 6 J cm-2 doses, respectively. The fluorescence microscopy and flow cytometry analysis showed that the four chlorin derivatives lead tumor cells to death predominantly by apoptosis during the treatment with light. Considering that the chlorins 6a-b exhibited good water solubility and high phototoxicity to the tumor cells, we suggested that these tetrapyrrolic molecules have the potential for clinical treatment in cancer by PDT. (AU)

• Processo FAPESP: 20/06874-6 - Aplicações das metodologias e tecnologias de síntese em regime de fluxo contínuo desenvolvidas no LQBO-UFSCar na preparação de moléculas com atividades biológicas e IFAs
• Beneficiário: Kleber Thiago de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
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• Processo FAPESP: 19/27176-8 - Fotocatálise assimétrica aplicada à síntese do medicamento Brivaracetam: abordagens sintéticas empregando tecnologias facilitadoras de síntese química
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• Modalidade de apoio: Auxílio à Pesquisa - Regular