Physiochemotherapy alginate-based hydrogel inhibiting lipogenesis through antioxidant and ant-inflammatory effects for obesity treatment.

Obesity is strongly associated with hypertension, hyperglycemia, insulin resistance, and other metabolic syndrome symptoms, emphasizing the urgent need for innovative therapeutic strategies. Physiochemotherapy, which combines the advantages of chemical and physical therapies, has attracted significant research interest. However, the precise outcomes and mechanisms of this integrative approach for obesity treatment remain poorly understood. In this study, we developed a physically photothermal nanocomposite hydrogel (termed SDAR) loaded with chemical resveratrol nanoparticles for obesity mitigation. SDAR was synthesized using polydopamine-functionalized sodium alginate, Zn, and resveratrol nanoparticles. The resveratrol nanoparticles exhibited a size distribution of 5-15 nm and a minor Zetal potential below 1.3 mV across varying pH conditions. The engineered SDAR hydrogel demonstrated stable photothermal performance with a steady temperature around 44 °C, high biocompatibility, strong antioxidant capacity (antioxidant rate of 93.7 %), and anti-inflammatory properties. In a lipid differentiation model, photothermal SDAR hydrogel administration effectively reduced intracellular reactive oxygen species (ROS) and inflammatory markers by over 50 % in 3T3-L1 preadipocytes. Furthermore, SDAR attenuated CCAAT/enhancer-binding protein beta (C/EBPβ) binding activity to downstream target genes, thereby inhibiting lipogenic differentiation. Collectively, the photothermal-responsive SDAR hydrogel presents a promising physiochemotherapy strategy for obesity treatment by suppressing lipogenesis.