A Multifunctional γ-Polyglutamic Acid Hydrogel for Combined Tumor Photothermal and Chemotherapy

Efficient and precise cancer therapy remains a challenge due to limitations in current treatment modalities. In this study, we developed a multifunctional hydrogel system that integrates photothermal therapy (PTT) and chemotherapy to achieve combined tumor treatment. The hydrogel, composed of γ-polyglutamic acid (γ-PGA), fifth-generation polyamide-amine dendrimers (G5), and polydopamine (PDA) nanoparticles, exhibits high photothermal conversion efficiency and temperature-responsive drug release properties. The hydrogel exhibited a high photothermal conversion efficiency of 45.6% under 808 nm near-infrared (NIR) irradiation. Drug release studies demonstrated a cumulative hydrophilic anticancer drug doxorubicin DOX release of 79.27% within 72 h under mild hyperthermia conditions (50 °C). In vivo experiments revealed a significant tumor inhibition rate of 82.3% with minimal systemic toxicity. Comprehensive in vitro and in vivo evaluations reveal that the hydrogel demonstrates excellent biocompatibility, photothermal stability, and biodegradability. Unlike conventional hydrogel systems, our γ-PGA-based hydrogel uniquely integrates a biocompatible and biodegradable polymer with polydopamine (PDA) nanoparticles, providing a smart and responsive platform for precise cancer therapy. This multifunctional hydrogel system represents a promising platform that combines PTT precision and chemotherapy efficacy, providing a robust strategy for advanced and safer cancer treatment.