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 H 2 O 2 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 ( • SO 4 – ) at the tumor site. The system coloads a metal catalyst Zn–Fe layered double hydroxide (ZnFe-LDH, ZFL) and a PMS donor (Na 2 S 2 O 8 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 ≡Fe IV ═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.