Comparison of the In Vitro Photodynamic Activity of the C1α and C1β Anomers of a Glucosylated Boron Dipyrromethene

Abstract

Photodynamic therapy (PDT) is an established treatment modality for a range of superficial and localized cancers. There has been tremendous interest in the development of advanced photosensitizers that exhibit superior photophysical properties, high tumor selectivity, and improved pharmacokinetics. Glucose is one of the well-studied targeting moieties that can deliver various therapeutic agents to cancer cells selectively via the Warburg effect. However, the use of glucosylated photosensitizers for targeted PDT has remained little studied and to the best of our knowledge, the PDT effect of the positional isomers of these conjugates has never been compared. We report herein the preparation and photophysical properties of the C1α and C1β anomers of a glucosylated boron dipyrromethene-based photosensitizer. The cellular uptake and photocytotoxicity of both anomers were also studied and compared using A549 human lung carcinoma cells and HEK293 human embryonic kidney cells. Interestingly, the cellular uptake of the C1α anomer was approximately 2-fold higher than that of the C1β anomer regardless of the cell type and incubation time. The uptake pathway of both anomers was also studied. It was found that they were internalized through energy-dependent receptor/protein-mediated endocytosis rather than the well-known glucose transporters and sodium-driven glucose symporters.

Toward Precise Antitumoral Photodynamic Therapy Using a Dual Receptor‐Mediated Bioorthogonal Activation Approach

“…Interestingly, when the cells were further incubated with 2 , only the biotin receptor‐ and EGFR‐positive A549 cells were killed effectively. The half‐maximal inhibitory concentration was determined to be 0.1 μM, which was lower compared with that for our previously reported BODIPY‐based photosensitizers [31a, 42] . The high photocytotoxicity against A549 cells could be attributed to the dual receptor‐mediated bioorthogonal activation of the photodynamic activity of 1 by 2 .…”

Toward Precise Antitumoral Photodynamic Therapy Using a Dual Receptor‐Mediated Bioorthogonal Activation Approach

“…Interestingly, when the cells were further incubated with 2 , only the biotin receptor‐ and EGFR‐positive A549 cells were killed effectively. The half‐maximal inhibitory concentration was determined to be 0.1 μM, which was lower compared with that for our previously reported BODIPY‐based photosensitizers [31a, 42] . The high photocytotoxicity against A549 cells could be attributed to the dual receptor‐mediated bioorthogonal activation of the photodynamic activity of 1 by 2 .…”

Glycosylated BODIPY- Incorporated Pt(II) Metallacycles for Targeted and Synergistic Chemo-Photodynamic Therapy

“…As mentioned in the Introduction, GLUT1 has been exploited as an important target for the delivery of theranostic agents against cancer . To examine the targeting effect of the glucose moieties in the triangular Pt(II)-BODIPY complex 1 , the cellular uptake of this metallacycle was studied using the GLUT1-positive HT29 human colorectal adenocarcinoma cells and A549 human lung carcinoma cells, as well as the non-cancerous human embryonic kidney cells HEK293 used as the negative control. , These cells were incubated with 1 (4 μM) for 1, 4, and 8 h, respectively, and then examined using confocal fluorescence microscopy. As shown in Figure a, bright green fluorescence due to 1 was observed in HT29 and A549 cells, while the fluorescence was much weaker in HEK293 cells after incubation for 1 h. The intensity was generally increased slightly upon prolonged incubation (to 4 and 8 h) for all of the three cell lines (Figure b,c, respectively).…”