A Spirocyclic BODIPY Photosensitizer with pH-Triggered Triplet-State Activation for Tumor-Selective Photodynamic Therapy

Abstract

Conventional photosensitizers for photodynamic therapy (PDT) suffer from poor tumor selectivity. Here, we develop BDP-I, a spirocyclic BODIPY-based photosensitizer that exploits the acidic tumor microenvironment (pH~6.5-6.8) to achieve selective activation. By integrating β-iodine atoms and electronwithdrawing vinyl groups with a meso-2-(hydroxymethyl)phenyl switching unit, BDP-I enables, for the first time, pH-triggered restoration of triplet-state-mediated reactive oxygen species generation (pKa = 6.87). This design affords selective phototoxicity in tumor cells over normal cells, establishing spirocyclic BODIPY as a promising scaffold for tumor-acidity-targeted PDT.