Iron sulfate-reinforced hydrogel reactors with glucose deprivation, serial reactive oxygen species generation, ferroptosis induction, and photothermal ablation for cancer therapy

Abstract

Glucose deprivation, hydroxyl radical generation, photothermal ablation, and ferroptosis induction-installed injectable hydrogel reactor was designed for multiple therapy of localized breast cancer. Iron sulfate (IS) was introduced to hydrogel reactor network for coordination with catechol groups of hyaluronic acid-catechol (HC) conjugate, photothermal conversion by reaction with catechols, Fenton-reaction-related hydroxyl radical production, and ferroptosis induction of cancer cells. Glucose oxidase (GOx) was incorporated in hydrogel reactor for the decomposition of glucose and production of H2O2. Following curing strategies were elaborately organized in the one-pot hydrogel reactor structure: i) starvation of cancer cells and self-supply of H2O2 by GOx, ii) hydroxyl radical generation (from H2O2) and ferroptosis induction by IS, and iii) photothermal therapy by catechol polymerization and iron ion-catechol binding. Exquisite arrangement of therapeutic modalities in HC-based hydrogel network by local injection to breast cancer was applied in this study. Also, the rheological properties of HC hydrogel were tuned by pH adjustment for endowing immediate and uniform gelation features, injection through single syringe, shear-thinning behaviors, and self-healing characteristics. It is expected that fabricated hydrogel reactor system can be used efficiently and safely for curing cancers following its local injection.