"One Stone, Four Birds" Ion Engineering to Fabricate Versatile Core-Shell Organosilica Nanoparticles for Intelligent Nanotheranostics.

Developing effective intelligent nanotheranostics is highly desirable for cancer treatment but remains challenging. In this study, an acidic tumor microenvironment-activated organosilica nanosystem, namely AD-Cu-DOX-HA, is straightforwardly constructed, which is composed of aggregation-induced emission (AIE)-active photosensitizer, copper ion-engineered aminosilica, direct coordination polymer of doxorubicin (DOX), and targeting component hyaluronic acid (HA). AD-Cu-DOX-HA is able to accurately distinguish cancer cells over normal cells; meanwhile, it simultaneously exhibits selective accumulation and copper ion-mediated rapid disassembly and turn-on fluorescence in tumor tissue, consequently achieving efficient tumor diagnosis and tumor-growth inhibition through fluorescence imaging-navigated synergetic photodynamic therapy, copper ion-mediated chemodynamic therapy, and DOX-enabled chemotherapy. This work thus brings fresh insight into the exploration of versatile theranostics and presents a momentous advance for potential clinical cancer treatment.