A Silicon-Rhodamine-Based Heavy-Atom-Free Photosensitizer for Mitochondria-targeted Photodynamic Therapy

Silicon-xanthene derivatives (SiXs) have gained popularity in the field of bioimaging due to their advantageous far-red to near-infrared (NIR) absorption and emission wavelengths, notable brightness (ε × Φ), inherent mitochondrial targeting properties and high photo-stability, making them an excellent candidate for photodynamic therapy (PDT). Nevertheless, the utilization of SiXs as photosensitizers (PSs) for PDT in cancer treatment remains largely unexplored, primarily due to their limited capacity to generate cytotoxic reactive oxygen species (ROS). However, the potential of SiXs in PDT warrants further investigation. In this study, utilizing the spin-orbit charge transfer-induced intersystem crossing (SOCT-ISC) mechanism, we reported one novel heavy-atom-free, mitochondria-targeted, silicon-rhodamine-based photosensitizer (SiR-PXZ), which demonstrated excellent biocompatibility, minimal dark toxicity, favorable water-solubility and stability, and considerable singlet oxygen quantum yield under 660 nm light irradiation (Φ_Δ = 0.16 in air-saturated PBS). Moreover, SiR-PXZ could be rapidly taken up by the mitochondria and efficiently induced apoptosis of cancer cells with an IC₅₀ value of 1.2 μM. The in vivo studies showed that SiR-PXZ exhibited excellent anti-tumor effects, making it potentially valuable for clinical application. This study offers a source of ideas for the construction of SiXs-based photosensitizers for photodynamic cancer treatment in the future.