Nanoscale Organic-Inorganic Hybrid Photosensitizers for Highly Effective Photodynamic Cancer Therapy

Recently, photodynamic therapy (PDT) has attracted significant attention as a minimally invasive approach for cancer treatment. Clinical applications of current photosensitizers are often limited by their poor water solubility, low singlet oxygen (¹O₂) quantum yields, long-term toxicity, instability, and complex nanostructures. Here, we report a rational design of polyhedral oligomeric silsesquioxanes (POSSs)-based porphyrin (PPP₅₀₀₀) used as an intrinsically nanoscale photosensitizer. In this strategy, inorganic 3D rigid block POSSs not only act as antiaggregate units but also provide conjugating reactive sites for further chemical modification. Without an additional carrier and formulation process, PPP₅₀₀₀ intrinsically shows high water solubility (∼40 mg/mL), good PDT efficiency, and more excellent anticancer performance compared to tetra(hydroxyphenyl)porphyrin (the parent compound of m-THPC, Foscan). Considering the organic nature of porphyrin and the biodegradable property of inorganic POSS scaffolds at physiological conditions, the present work may lead to a new generation of biodegradable and intrinsic PDT agents with overall performance superior to conventional agents in terms of ¹O₂ production efficiency, water solubility, structurally stability, photostability, and biocompatibility.