Efficient radical generator with NIR emission by donor modulation for mitochondria-targeted photodynamic therapy

Development of NIR type I photosensitizers (PSs) that can specifically target subcellular organelles remains a significant challenge in photodynamic therapy (PDT). In this work, two D–π–A PSs named TPE-IN and TPA-IN were constructed via the strategy of changing donors. In detail, replacing donor group tetraphenylethylene ( TPE-IN ) with triphenylamine ( TPA-IN ) could extend the emission wavelength of PSs into the NIR-I region. Meanwhile, the singlet-triplet energy gap (Δ E ST  = 0.53 eV) of PSs was also narrowed, which efficiently promoted the production of superoxide anion radical (O 2 − ) and hydroxyl radical ( OH), especially for TPA-IN . Further mechanistic studies demonstrated that the generation of OH mainly relied on the cascaded electron-transfer process mediated by the Haber-Weiss reaction (O 2 −  → H 2 O 2  →  OH). More importantly, TPA-IN could specifically accumulate in mitochondria through electrostatic interactions ( Pr  = 0.81), which could decrease mitochondrial membrane potential, inducing cell late apoptosis (95.8 %) upon light exposure. This study established innovative theoretical and technological groundwork for designing high-efficiency, precision-targeted optical theranostic agents aimed at eliminating cancer cells.