Lysosome-localization and tumor-targeting of novel photosensitizers enhance the ablation of cancer

Lysosomes are promising therapeutic targets for cancer therapy due to their essential function and increased vulnerability in cancer cells. Herein, we report a new category of cationic photosensitizers (compounds 1–3) containing a quaternary ammonium group. These photosensitizers exhibited selective uptake on cancer cells (about three times compared to the normal cells), lysosome-specific localization (Pearson's coefficients greater than 0.85), remarkable phototoxicity (IC₅₀ are in the range of dozens of nM), and at the same time, favorable biosafety. Mechanically, these tumor-targeting photosensitizers function as light-controlled “bombs”, inducing lysosomal membrane permeabilization (LMP), ultimately resulting in apoptosis of cancer cells. In vivo, compound 1 (a representative of these novel photosensitizers) accumulated predominantly in and visualized tumors implanted on mice. Upon exposure to near-infrared light irradiation (50 J/cm²), the compound effectively ablated the tumor at a low dose of 2 mg/kg. Our results demonstrate a novel class of photosensitizers showing potential for integrated cancer diagnosis and photodynamic treatment.