Ferrocene and glucose oxidase-installed multifunctional hydrogel reactors for local cancer therapy

A hyaluronic acid (HA)-based one-pot hydrogel reactor with single syringe injection and immediate gelation was developed for starvation therapy (ST), chemodynamic therapy (CDT), ferroptosis, and photothermal therapy (PTT) against breast cancer. A rheologically tuned hydrogel network, composed of HA-phenylboronic acid (HP) and HA-dopamine (HD), was designed by introducing a boronate ester linkage (phenylboronic acid-dopamine interaction) and polydopamine bond (pH control). Ferrocene (Fc)-conjugated HP (Fc-HP) was synthesized to achieve ferroptosis, Fenton reaction-involved toxic hydroxyl radical ((OH)-O-center dot) generation, and photothermal ablation in cancer therapy. Glucose oxidase (GOx) was entrapped in the pH-modulated Fc-HP (Fc-HP degrees)/HD hydrogel network for converting intracellular glucose to H2O2 to enable its own supply. The GOx/Fc combination-installed hydrogel reactor system can provide sustained ST/CDT/PTT functions along with ferroptosis. Injection of Fc-HP degrees/HD/GOx hydrogel with single-syringe injectability, shear-thinning feature, and self-healing capability offered a slow biodegradation rate and high safety profiles. Peritumorally injected Fc-HP degrees/HD/GOx hydrogel also efficiently suppressed the growth of breast cancer based on multifunctional therapeutic approaches with reduced dosing frequency. Hyperthermia induced by near-infrared (NIR) laser absorption may amplify the therapeutic effects of free radicals. It is expected that this Fc-HP degrees/HD/GOx hydrogel system can be applied to local cancer therapy with high efficacy and safety profiles.

Automated summary

This study developed a hyaluronic acid-based hydrogel reactor that can be formed into a gel with a single syringe injection for multiple therapies against breast cancer. The hydrogel system provides sustained therapeutic functions and high safety profiles.