Development of glyco‐conjugated chlorin e6 for photodynamic therapy

Abstract

PDT (photodynamic therapy) has much attracted as less invasive method for treating cancer.1 To increase the antitumor effects and shorten the light shielding duration, we developed third‐generation photosensitizers for PDT. We have focused much attention to the glyco‐conjugation of chlorin derivatives mainly for the purpose of improving their biocompatibility and tumor selectivity. Generally, cancer cells uptake higher level of glucose than normal cells in a phenomenon known as Warburg's effect, which is also utilized in positron emission tomography (19FDG‐PET‐CT). We developed a number of glyco‐conjugated chlorins resulting finally in Glc‐chlorin e6, which showed the strongest antitumor effects in PDT ever reported for synthesized glyco‐conjugated chlorins.2 Furthermore, Glc‐chlorin e6 is discharged very fast from the body. We also confirmed extremely promising antitumor effects of 40% CR in vivo under conditions that killed all mice in the comparable TS (talaporfin sodium) PDT group. We have also already synthesized 14C‐labeled Glc‐chlorin e6 and examined its pharmacokinetics in rat to reveal a plasma half‐life of 42.65 h, which is shorted than that of TS. In rat, 14C‐labeled Glc‐chlorin e6 was mainly discharged in bile and faster than TS. Single time toxicity test of Glc‐chlorin e6 in mouse also showed the lowest published lethal dose of 250 mg/kg. From these findings, we consider that Glc‐chlorin e6 is the ideal sugar for conjugating to chlorin, evidenced by the remarkable antitumor PDT effects, rapid excretion, and low toxicity demonstrated herein. Glc‐chlorin e6 is considered to be the best candidate PS thus far for third‐generation PDT and we plan to continue with our investigatory studies with the ultimate aim of clinical trials. We examined the efficacy of PDT with Glc‐chlorin e6 for tumor‐bearing dogs.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.