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

Le résumé fourni par la source

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.

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