Antitumor effects of a novel glucose-conjugated bacteriochlorin for photodynamic therapy

Abstract

Abstract Photodynamic therapy (PDT) is a minimally invasive cancer treatment that employs photosensitizers (PSs) activated by light to generate cytotoxic reactive oxygen species (ROS). Talaporfin sodium (TS), widely used in Japan, has shown limited efficacy in advanced tumors, highlighting the need for novel PSs. We developed a glucose-conjugated bacteriochlorin derivative, Glc-TFPB, designed to enhance tumor selectivity via the Warburg effect and to enable deep tissue penetration owing to its near-infrared absorption. In vitro, Glc-TFPB exhibited time-dependent cellular uptake, predominantly in lysosomes, and induced significant ROS generation and apoptosis upon PDT. Compared with TS, Glc-TFPB-PDT demonstrated markedly higher cytotoxicity 24 h after administration (IC50: 1.10 µM vs 13.60 µM). In vivo fluorescence analysis revealed peak tumor accumulation at 24 h after administration, consistent with optimal treatment timing. PDT with Glc-TFPB significantly suppressed tumor growth in xenografted mice, with greater efficacy at 24 h than at 2 h after administration. These findings indicate that Glc-TFPB is a promising next-generation PS with improved tumor selectivity, deeper tissue penetration, and superior photodynamic efficacy, supporting its potential for clinical translation.