“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.