Biodegradable Multifunctional Nanotheranostic Based on AgS-Doped Hollow BSA-SiO for Enhancing ROS-Feedback Synergistic Antitumor Therapy.

Stimuli-responsive silica nanoparticles are an attractive therapeutic agent for effective tumor ablation, but the responsiveness of silica nanoagents is limited by intrastimulation level and silica framework structure. Herein, a biodegradable hollow SiO-based nanosystem (AgS-GOx@BHS NYs) is developed by a novel one-step dual-template (bovine serum albumin (BSA) and cetyltrimethylammonium bromide (CTAB)) synthetic strategy for image-guided therapy. The AgS-GOx@BHS NYs can be specifically activated in the tumor microenvironment via a self-feedback mechanism to achieve reactive oxygen species (ROS)-induced multistep therapy. In response to the inherent acidity and HO at the tumor sites, AgS-GOx@BHS would accelerate the structural degradation while releasing glucose oxidase (GOx), which could efficiently deplete intratumoral glucose to copious amounts of gluconic acid and HO. More importantly, the sufficient HO not only acts as a reactant to generate Ag from AgS for metal-ion therapy and improves the oxidative stress but also combines with gluconic acid results in the self-accelerating degradation process. Moreover, the released AgS nanoparticles can help the AgS-GOx@BHS NYs realize the second near-infrared window fluorescence (NIR-II FL) and photoacoustic (PA) imaging-guided precise photothermal therapy (PTT). Taken together, the development of a self-feedback nanosystem may open up a new dimension for a highly effective multistep tumor therapy.