Effect of pH on uptake and photodynamic action of chlorin p6 on human colon and breast adenocarcinoma cell lines

Abstract

The effect of reducing the extracellular pH from 7.4 to 6.0 on the uptake and photosensitivity of chlorin p6, a potential photosensitising drug, has been investigated using two mammalian cell lines, human colon (Colo-205) and breast (MCF-7) adenocarcinoma cells. In Colo-205 cells, the uptake and phototoxicity of chlorin p6 was observed to increase as the pH of the incubation medium decreased. For light doses of up to [similar]6 kJ m(-2), although there was no evidence of mitochondrial damage, a significant reduction in Neutral Red uptake was observed, signifying damage to lysosomes. At higher light doses, significant mitochondrial damage was observed, accompanied by saturation of the lysosomal damage. This suggests light-induced relocalization of the photosensitizer from lysosomes to mitochondria. Furthermore, it was found that for a given light dose, lysosomes exhibit greater photosensitivity at lower pH. Since chlorin p6 is known to aggregate at pH 6.0, this observation suggests that the dye accumulation in these cells mainly takes place through endocytosis. In contrast, no significant variation in uptake, photosensitivity, and sites of photodamage was observed for MCF-7 cells at different extracellular pH. Additionally, the lower photosensitivity of lysosomes as compared to mitochondria in these cells suggests chlorin p6 is taken up through diffusion rather than endocytosis.

The photodynamic effect of methylene blue and toluidine blue on Candida albicans is dependent on medium conditions

“…Böhmer and Morstyn (1985) showed that the uptake of hematoporphyrin derivative from normal and malignant cells increased when the medium pH was decreased from 7.4 to 6.0. This effect was also described by Sharma et al (2004), who demonstrated that both the uptake and phototoxicity of chlorin p6 were increased as the pH of the incubation medium decreased, in human colon adenocarcinoma cells. Uzdensky et al (2007) recently studied the involvement of Ca 2+ -mediated signaling pathways in photooxidative injury of neurons and glia.…”

Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development

“…The accumulation of chlorin e6 in A549 and A549/CDDP cell lines at 4°C was significantly lower than that at 37°C, indicating the temperature dependence of the uptake of chlorin e6 in these cell lines. Involvement of passive diffusion and/or the endocytic pathway in chlorin e6 uptake has been indicated,29–31 but the molecular mechanisms underlying the cellular uptake remain to be fully elucidated. Recently, chlorin e6 and hematoporphyrin were reported to competitively inhibit the organic anion transporting polypeptide 1B1 (OATP1B1)‐mediated uptake,32 although the paper did not show whether the photosensitizers are transported by OATP1B1.…”

Effect of Complexing with Silica Nanoparticles on the Phototoxicty of Some Photosensitisers

“…This enabl Cp 6 has three ionizable carboxylic a protonation-deprotonation of the three Figure 5. r as it has a strong absorption band at ~660 nm which ood triplet yield and good tumor selectivity [16][17][18][19]. Our p eritoneally administered free Cp 6 can cause complete nec e <100 mm 3 in hamster cheek pouch animal model [20] ug, only superficial necrosis and size reduction was observ used to achieve higher drug delivery in tumor because o led complete regression of bigger tumors ( 1000 mm 3 ).…”

“…In aqueous medium at physiological pH the drug exists predominantly as negatively charged (i.e. closer to structure D in Figure 5) and as the pH is progressively lowered, successive protonation of the carboxyl groups (forming structures C to A in Scheme 1) makes it hydrophobic leading to aggregation of the drug which has been shown to enhance its uptake in human colon adenocarcinoma (Colo-205) cells [19]. The change in acid/base ionization equilibrium of the PS also leads to significant changes in its absorption and fluorescence characteristics.…”