Photosensitizer (PS)/polyhedral oligomeric silsesquioxane (POSS)-crosslinked nanohybrids for enhanced imaging-guided photodynamic cancer therapy

Photodynamic therapy (PDT) has drawn extensive attention as a promising cancer treatment modality. However, most PDT nanoagents suffer from insufficient drug loading capacity, a severe self-quenching effect, premature release of drugs and/or potential toxicity. Herein, we rationally designed an inorganic-organic nanohybrid with high drug loading capacity and superior chemical stability for enhanced PDT. Polyhedral oligomeric silsesquioxane (POSS), an amine-containing cage-shaped building block, was crosslinked with chlorin e6 (Ce6), a carboxyl-containing photosensitizer, via the amine-carboxyl reaction. Polyethylene glycol (PEG) polymers were further modified on the surface of the nanoparticle to improve the aqueous dispersibility and prolong the circulation time of the final nanoconstruct (POSS-Ce6-PEG). The as-prepared POSS-Ce6-PEG has a considerably high loading rate of Ce6 (19.8 wt%) with desirable fluorescence emission and singlet oxygen generation. Besides, in vitro experiments revealed that the nanoagent exhibited enhanced cellular uptake and a preferred intracellular accumulation within mitochondria and the endoplasmic reticulum, resulting in high anticancer efficiency under light irradiation. Furthermore, in vivo imaging-guided PDT was also successfully achieved, showing the effective tumor targeting and ablation ability of POSS-Ce6-PEG. More importantly, the nanoagent possesses negligible dark cytotoxicity and systemic side effects. Therefore, POSS-Ce6-PEG as an eligible PDT theranostic agent holds great potential in clinical applications.