A Multitarget Synergistic Core‐Shell Nanogel for Experimental Periodontitis Treatment

Abstract Periodontitis, a multifactorial inflammatory disease affecting periodontal tissues, threatens the oral health of millions worldwide. Traditional single‐target treatments are insufficient for addressing the disease's complex multifactorial pathological mechanisms. This study presents a novel multitarget synergistic core‐shell nanogel, a type of biocompatible nanosized polymeric material with hydrogel‐like properties designed for periodontitis treatment. The nanogel comprises a biocompatible quaternized chitosan‐polydopamine (CSQ–PDA) shell and resveratrol (RES)‐loaded casein nanomicelles (R@C) core. Nanomicelles can self‐assemble in water to enhance the solubility of RES, thus improving its functional properties in vivo. The CSQ–PDA shell can be self‐polymerized and noncovalently bound to R@C to form (R@C)PC nanogel without any organic reagents. This design allows the nanogel to remodel the immune microenvironment by promoting macrophage M2 polarization, downregulating proinflammatory factors, and upregulating anti‐inflammatory factors. Its significant antioxidant capacity can also upregulate superoxide dismutase to scavenge reactive oxygen species. Notably, this cationic nanogel can target and bind bacteria by electrostatic interaction and has an effective photothermal conversion ability for antimicrobial photothermal therapy. Its high adhesion and minimal fluidity ensure the precise, sustained treatment of periodontitis. The results demonstrate that this nanogel is a promising multitarget synergistic nanoplatform for enhancing periodontitis treatment efficacy.