Invention of a novel photodynamic therapy for tumors using a photosensitizing PI3K inhibitor

Abstract

XL147 (SAR245408, pilaralisib), an ATP-competitive pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, is a promising new anticancer drug. We examined the effect of the PI3K inhibitor on PC3 prostate cancer cells under a fluorescence microscope and found that XL147-treated cancer cells are rapidly injured by blue wavelength (430 nm) light irradiation. During the irradiation, the cancer cells treated with 0.2-2 lM XL147 showed cell surface blebbing and cytoplasmic vacuolation and died within 15 min. The extent of cell injury/death was dependent on the dose of XL147 and the light power of the irradiation. These findings suggest that XL147 might act as a photosensitizing reagent in photodynamic therapy (PDT) for cancer. Moreover, the cytotoxic effect of photosensitized XL147 was reduced by pretreatment with other ATP-competitive PI3K inhibitors such as LY294002, suggesting that the cytotoxic effect of photosensitized XL147 is facilitated by binding to PI3K in cells. In a singlecell illumination analysis using a fluorescent probe to identify reactive oxygen species (ROS), significantly increased ROS production was observed in the XL147-treated cells when the cell was illuminated with blue light. Taken together, it is conceivable that XL147, which is preferentially accumulated in cancer cells, could be photosensitized by blue light to produce ROS to kill cancer cells. This study will open up new possibilities for PDT using anticancer drugs.

Cutaneous Toxicities of PI3K Inhibitors: A Series of Two Cases and Review of the Literature

“…1 Of note, PI3K inhibitors are effective photosensitizing agents and demonstrated potential utility in photodynamic therapy for cancer, thereby suggesting a possible mechanism underlying the photo-accentuated cutaneous toxicity noted in this case series. 13 According to CTCAE guidelines, eruptions should be stratified by severity corresponding to body surface area involvement. Lower grade toxicities can be managed with high potency topical corticosteroids and antihistamines, whereas severe and persistent toxicities require systemic corticosteroids and possible interruption of PI3K inhibitor therapy.…”

An In Vitro Study of the Photodynamic Effectiveness of GO-Ag Nanocomposites against Human Breast Cancer Cells

“…Afterward, the cells were exposed for 15 min at a Laser light of 430-nm blue wavelength, irradiated with 100 J/cm 2 . After being further cultured for another 24 h, the relative cell viabilities were then measured by the MTT assay [ 36 ].…”