Work

Novel one−/two-photon excited β-carboline/quinolinium photosensitizers for hypoxia-resistant tumor photodynamic therapy through apoptosis and necrosis

Year: 2025

Type: article

Abstract: Photodynamic therapy (PDT) represents an innovative modality that employs photosensitizer for the treatment of tumors, dermatological conditions, and vascular disorders. Herein, a series of novel photosensitizers 2a-e were designed and synthesized by incorporating quinolinium into the β-carboline. In particular, photosensitizer 2d generated a large amount of type-I/-II active oxygen species, including 1 O 2 , •O 2 − , and •OH under one−/two-photon excitation. Furthermore, 2d effectively overcame the tumor hypoxic microenvironment and exhibited strong one−/two-photon photodynamic activities against HT29 cells (IC 50 s = 0.18–0.56 μM, PIs = 88–263). Additionally, 2d could significantly induce cancer cell apoptosis via reducing Bcl-2 and increasing Bax/Cleaved-caspase-3, and simultaneously promote programmed necrosis through boosting P-MLKL and P-RIPK1/3 expression. In vivo experiments substantiated that 2d powerfully suppressed colonic tumor growth under one−/two-photon irradiation (suppression rates 77–91 %). Therefore, this work may provide an effective approach for designing novel β-carboline/quinolinium photosensitizers and present a promising prospect in the field of one−/two-photon tumor photodynamic therapy.

Source: Bioorganic Chemistry

DOI: 10.1016/j.bioorg.2025.108538