Silk Fibroin-Based Injectable Hydrogel Encapsulated with Layered Double Hydroxide for Tumor Therapy via Continuous Radical Generation

In recent decades, reactive oxygen species (ROS)-based tumor therapies, including photodynamic therapy (PDT) and chemodynamic therapy (CDT), have gained widespread attention. However, factors such as limited light penetration depth, hypoxic tumor environments, and insufficient H2O2 levels restrict their effectiveness. To address this, we developed an injectable silk fibroin (SF)-based gel system, NSO/ZFL@SLH, leveraging peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) to generate radicals such as sulfate radical (•SO4–) at the tumor site. The system coloads a metal catalyst Zn–Fe layered double hydroxide (ZnFe-LDH, ZFL) and a PMS donor (Na2S2O8 nanoparticles, NSO) into an SF solution with lauroyl arginine ethyl hydrochloride (LAE). LAE rapidly induces the β-sheet formation of SF. Moreover, prepared by introducing Zn(OH)2 into an Fe(III)-based catalyst, Zn(OH)2 provides a neutral microenvironment at the phase interface. This microenvironment enables efficient activation of PMS at the slightly acidic tumor site, continuously generating ≡FeIV═O. Consequently, it facilitates the Fe(II)/PMS system’s cycling from Fe(II) to Fe(III) and ensures the continuous production of active radicals. In vitro and in vivo experiments demonstrate that NSO/ZFL@SLH achieves rapid gelation, effective radical production, and long-term tumor suppression. This study holds positive guiding significance for the development of ROS-based antitumor therapies and the expansion of PMS-based AOPs in biomedical applications.