Ruthenium-gallic acid nanozymes encapsulated in 3D bioprintable photosensitive hydrogels for synergistic PTT/CDT therapy of glioblastoma

Confronted with the clinical challenges of glioma treatment, including incomplete resection and therapeutic resistance, we developed an integrative bioprinting strategy. At the core of our approach is a 3D-bioprintable, photosensitive hydrogel loaded with ruthenium-gallic acid (Ru-GA) nanoenzymes. This system is designed to seamlessly combine chemodynamic therapy (CDT) with photothermal therapy (PTT) to achieve precise and synergistic treatment of glioblastoma multiforme (GBM). Ru-GA, synthesized via Ru³⁺-gallic acid coordination, has potent peroxidase-like activity to catalyze reactive oxygen species generation from H₂O₂ in the tumor microenvironment. It also efficiently depletes glutathione to disrupt tumor redox homeostasis, and exhibits excellent near-infrared absorption and photothermal conversion efficiency. Based on GelMA and HAMA, the hydrogel is liquid at 37 °C and has the ability to be injected into tumor tissue, ensuring localized retention and sustained action of Ru-GA at tumor sites. In vitro tests verified Ru-GA kills GL261 glioma cells via CDT, and combining it with PTT further inhibits tumor cell proliferation, migration, and clonogenicity while boosting apoptosis. In 3D bioprinted tumor models, the hydrogel suppresses tumor cell aggregation and viability effectively. In vivo experiments showed intratumoral hydrogel injection plus near-infrared irradiation raises tumor temperature to 55 °C, exerting synergistic PTT/CDT effects to significantly inhibit tumor growth with excellent biosafety. Mechanistically, this therapy activates inflammatory pathways and inhibits metastasis-related signaling, offering a safe, efficient GBM treatment and laying a foundation for clinical translation of nanocatalyst-based photosensitive hydrogels.