Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line

Abstract

Melanoma is the most dangerous form of skin cancer, with an abrupt growth of its incidence over the last years. It is extremely resistant to traditional treatments such as chemotherapy and radiotherapy, but therapies for this cancer are gaining attention. Photodynamic therapy (PDT) is considered an effective modality to treat several types of skin cancers and can offer the possibility to treat one of the most aggressive ones: melanoma. In this work, the effect of PDT on a melanotic cell line (B16F10 cells) was assessed by exposing cultured cells to 5,10,15-tris(pentafluorophenyl)-20-(4pyridyl)porphyrin (PS1) and to its chlorin (PS2) and isobacteriochlorin (PS3) corresponding derivatives and red LED light (λ = 660 ± 20 nm). The PDT effect in the cells' viability was measured using the MTT assay. The cell apoptosis was quantified by flow cytometry, and the subcellular localization of the photosensitizer was determined by fluorescence microscopy. In addition, the ability of PS2 to generate superoxide radicals was qualitatively assessed by tyrosine nitration. The results show that the efficiency of the PDT process is dependent on the structure of the PS and on their ability to produce singlet oxygen. Besides that, the photoactivation efficiency is highly dependent on the cellular sublocalization of the PS and on its cellular uptake and singlet oxygen production. We also found that the resistant cell line B16F10 has distinctive chlorin, isobacteriochlorin, or porphyrin-specific resistance profiles. Furthermore, it is shown that the highly fluorescent chlorin derivative PS2 can also be considered in imaging diagnostics.

Porphyrin Photosensitizers Grafted in Cellulose Supports: A Review

“…Naturally occurring chlorophylls and bacteriochlorophylls are essential constituents of plants and bacteria, often called the “pigments of life” [ 134 , 135 ] owing to their important role in photosynthetic processes. Nowadays, their synthetic counterparts also present multiple applications essentially due to their absorbance of light in a broad range of the spectrum, particularly in the red (chlorins) and near infra-red region, NIR (bacteriochlorins) [ 65 , 143 , 144 , 145 , 146 ]. Intense red and NIR photons absorption is a desirable feature for biomedical applications (Imaging, PDT, aPDT), since the phototherapeutic window (650–900 nm) for electromagnetic radiation is the most penetrating and least harmful to human tissues [ 147 , 148 ].…”

Synthesis of chlorins and bacteriochlorins from cycloaddition reactions with porphyrins

“…Considering that photodynamic therapy (PDT) can be an effective modality to treat several types of skin cancers, namely the most aggressive ones like melanoma, Castro et al 61 decided to revisit the reaction of 5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)porphyrin 52 with the azomethine ylide AZ1 and to evaluate the photodynamic action of the resulting chlorin 53 and isobacteriochlorin 54 (Figure 13) towards the melanotic cell line (B16F10). For comparison, the studies were also extended to the starting porphyrin 52.…”

Recent Photosensitizer Developments, Delivery Strategies and Combination‐based Approaches for Photodynamic Therapy†

“…Castro et al . (27) synthesized chlorin derivatives using 1,3‐dipolar cycloadditions on 5,10,15‐tris(pentafluorophenyl)‐20‐(4‐pyridyl) porphyrin, resulting in enhanced singlet oxygen generation ( φ Δ values from 0.65 to 0.81) with good photostability and with relatively strong absorption band in 650 nm. The authors reported that the reduction of one of the β‐pyrrolic because of the introduction of a pyrrolidine group is responsible for the intense absorption in 650 nm.…”

“…Chemical structures of Porphyrin derivatives. Summarized for references (27,41,42). [Colour figure can be viewed at wileyonlinelibrary.com]…”