Prolonged lipid oxidation after photodynamic treatment. Study with oxidation‐sensitive probe C11‐BODIPY^581/591

Abstract

Photodynamic treatment (PDT) is an emerging procedure for the therapy of cancer, based on photosensitizers, compounds that generate highly reactive oxygen species on illumination with visible light. Photodynamic peroxidation of cellular lipids is a consequence of PDT associated with cytolethality. We used chloromethyl dichlorodihydrofluorescein diacetate and a novel fluorescent ratiometric oxidation-sensitive probe, C11-BODIPY 581/591 (C11-BO), which reports on lipid peroxidation, for visualizing oxidative stress in cells subjected to PDT with a phthalocyanine photosensitizer Pc4. With C11-BO loaded into the cells before or immediately after PDT, we observed a prolonged oxidation, which continued up to 30 min after illumination. In contrast, H 2 O 2 caused oxidation of C11-BO only when the cells were in direct contact with H 2 O 2 . PDT-induced oxidative stress was most pronounced in vesicular perinuclear organelles, most likely photodamaged lysosomes. We hypothesize that the lysosomal localization of the prolonged oxidative stress is a consequence of the presence of redox-active iron in lysosomes. In conclusion, we have found that oxidative stress induced in cells by PDT differs from one induced by H 2 O 2 in respect of induction of prolonged oxidation of lipids.

Photochemical Internalization of Tamoxifens Transported by a “Trojan‐Horse” Nanoconjugate into Breast‐Cancer Cell Lines

“…[14] Thus,the present results are consistent with the photochemically induced release of tamoxifen from mTHPPbCD within the endocytic vesicles.…”

Photochemical Internalization of Tamoxifens Transported by a “Trojan‐Horse” Nanoconjugate into Breast‐Cancer Cell Lines

“…The PCIinduced translocation of drugs and the photosensitizer itself into the cytosol has been found to take some time and may take as long as 1 h. [13] The singlet oxygen formed has a very short lifetime (submicrosecond level) but induces lipidperoxidation chain reactions that may last for approximately 20-40 min. [14] Thus, the present results are consistent with the photochemically induced release of tamoxifen from mTHPPbCD within the endocytic vesicles.…”

Photolon™, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis

“…A recent study showed that after treatment with the photosensitiser, Pc4, ROS production was most pronounced in lysosomes, even though the photosensitiser itself was not specifically localised to lysosomes (Sakharov, Elstak, Chernyak, & Wirtz, 2005). These authors propose that lysosomes have a specific environment which makes them very susceptible targets for reaction oxygen species, and the attack of ROS on lipids in the lysosomes leads to lipid peroxidation.…”