Subcellular Phototoxicity of Photofrin-II and Lutetium Texaphyrin in Cells In Vitro

Abstract

Abstract. Three cell types including bovine pulmonary artery endothelium cells (CPAE), rat kangaroo kidney cells (PTK 2 ), and human larynx epidermoid carcinoma cells (Hep-2) were used to study subcellular localisation and phototoxicity of Photofrin-II and lutetium texaphyrin (Lu Tex). Cells were examined for fluorescence after administration of the photosensitisers. Subcellular regions were exposed with a laser microbeam system that used an argon ion laser pumped dye laser generating a 630 nm for Photofrin-II and 730 nm for Lu Tex. Fluorescence detection suggests that the Photofrin-II is bound primarily to the mitochondria with some di#use fluorescence in the rest of the cytoplasm. The fluorescence in Lu Tex treated cells appears to be localised to the lysosomes. The percentage of damaged cells following light exposure to the di#erent subcellular regions after Photofrin-II or Lu Tex treatment demonstrates that the nuclear region was the most sensitive target followed by the perinuclear region and peripheral cytoplasm region.

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

“…These data taken together clearly indicate that NLS-mediated nuclear localization of PSs enhances their activities, again confirming that the nucleus is a hypersensitive site for photodynamic damage (1,3,4,48,49). The cytotoxic activity of the MRT-linked PSs exceeded free PSs by several orders of magnitude.…”

Chromosomes are target sites for photodynamic therapy as demonstrated by subcellular laser microirradiation

“…This observation is consistent with previous studies demonstrating that the interphase nuclei of cells treated with ALA, Photofrin and Lutetium Texaphyrin were more light sensitive than other cell regions [13,14]. However, those studies were on interphase cells.…”

“…However, this increase could be due to either more ALA in the cell and thus more Protoporphyrin IX, or a higher conversion efficiency of ALA to Protoporphyrin IX. As noted previously [13,14], the most sensitive region of the cell has the least amount of detectable fluorescence. The same observation is made in the present study: the chromosomes are the most sensitive targets and no fluorescence can be detected with the sensitive cooled CCD system.…”

“…One such study by Morena and Salet [12] confirmed that in cardiac myocytes, the mitochondria were primary target sites for PDT. Recent studies demonstrated that in cells treated with several different photosensitizers, the interphase nucleus was the most sensitive target site, followed by the perinuclear cytoplasm, and finally the peripheral cytoplasm [13,14]. It was surprising to find such a high nuclear sensitivity because the highest level of sensitizer fluorescence was found in the cytoplasm around the nucleus.…”

Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets

“…When used for photodynamic therapy, PSs are a class of drugs that would derive significant benefit from being precisely delivered into the nuclei of target cells. The cytotoxicity of PSs is critically dependent on their delivery into the cell nucleus, because it is the most vulnerable intracellular compartment to ROS, which are the active agent for PS photodynamic action but have a tissue range of only 20–40 nm [166] (See: Drugs for intracellular targeting). Because of the potential for making major gains in therapeutic effectiveness of the PSs by enhancing its nuclear delivery, the efficacy of PS-MNT conjugates was studied in vitro and in vivo [29].…”