Supritha Muppuri, Yu-I Hsu, Hiroshi Uyama
Temperature regulates biochemical reactions, and controlled hyperthermia has been widely investigated for therapeutic applications. However, conventional hyperthermia is limited by non-specific heat distribution, which can damage surrounding healthy tissues. Photothermal therapy (PTT) enables localized heat generation under near-infrared (NIR) irradiation, although most reported PTT systems involve exogenous nanomaterials that require complex synthesis, surface functionalization, or integration with carrier systems to improve dispersion and retention at the target site. These modifications increase material complexity and may introduce toxicity concerns. Herein, poly(γ-glutamic acid)-tyramine (PGA-Tyr) hydrogels were prepared via Fenton reaction-mediated crosslinking, in which dityramine bonds formed the hydrogel network and in situ-generated ferric ions facilitated NIR-to-thermal energy conversion. The effects of iron(II) chloride (FeCl2), hydrogen peroxide (H2O2), and the degree of substitution (DS) of PGA-Tyr on gelation kinetics, mechanical properties, swelling behavior, and pore structure were systematically investigated. Ferric ion-containing hydrogels demonstrated efficient photothermal conversion, and the temperature increased to approximately 52.5-53.1 °C under NIR irradiation. Futhermore, optimization of the hydrogel formulation increased the photothermal conversion efficiency from ∼16% to 36.52%, with stable performance over repeated irradiation cycles. Hydrogel network density and ferric ion content regulated light penetration and heat retention, thereby enabling efficient thermal regulation. Increasing the network density improved hydrogel stability, whereas enzymatic treatment accelerated degradation. Overall, Fenton-mediated PGA-Tyr hydrogels exhibit tunable mechanical, swelling, and photothermal properties and provide a material platform for further biological evaluation in photothermal biomedical applications.