A Dual-Functional PEG-Tyrosine Hydrogel with Photothermal Effect and Antioxidant Capacity for Cancer Therapy and Tissue Regeneration

Abstract Achieving optimal tumor eradication while minimizing off-target toxicity and enhancing patient recovery remains a central challenge in translational oncology. Traditional therapies such as radiotherapy and chemotherapy are associated with systemic toxicities and resistance, compromising outcomes. Photothermal therapy provides spatial targeting and a minimally invasive approach but risks collateral tissue damage, particularly to skin. We report an injectable, biodegradable PEG-tyrosine hydrogel with oxidative modification (PETyrO) designed for dual-function tumor photothermal therapy and post-treatment wound regeneration. PETyrO is prepared in two steps: (i) ring-opening polymerization of L-tyrosine N-carboxyanhydride (Tyr-NCA) monomers, followed by (ii) enzymatic oxidation using tyrosinase. The hydrogel forms at a final concentration of 100 mg/mL before injection. Owing to its phenolic groups, PETyrO exhibits pronounced reactive oxygen species (ROS) scavenging capacity, promoting epithelial regeneration at treatment sites. In summary, the melanin-like, biocompatible system shows minimal cytotoxicity, achieves a photothermal conversion efficiency of 36% at 808 nm, and integrates ROS scavenging with wound-healing properties. More importantly, unlike traditional dopamine-based hydrogels, this peptide hydrogel features a well-defined structural framework and can degrade gradually in vivo. Through sequential control, it achieves tunable and repeatable structures and mechanical properties, increasing its potential for clinical translation. This multifunctional biomaterial offers a new paradigm for dual therapeutic capabilities.