Bacterial biofilm colonization and persistent chronic inflammation in periodontitis cause periodontal tissue destruction and eventual tooth loss. Bacterial biofilms disruption and immune cell metabolism reprogramming are critical for the treatment of periodontitis. Herein, we developed an injectable MXene-based hydrogel (GQM), composed of oxidized gellan gum, quaternized chitosan, and magnesium–tannic acid-modified MXene nanosheets (MTA-Mg), which serves as a flexible scaffold for targeted delivery of MTA-Mg within periodontal pockets. The GQM hydrogels can be injected into periodontal pockets and targetedly deliver MTA-Mg, which disrupts the dense biofilm efficiently by photothermal effect, while the bacteria are killed through the electrostatic interaction and charge neutralization from quaternized chitosan. MTA-Mg nanosheets serve as interfacial electron transfer to activate oxidative phosphorylation pathway, while delivering the magnesium and tannic acid to improve mitochondrial function, which reprogram the immune cell metabolism by inducing macrophage toward the M2 phenotype. The rat periodontitis model demonstrated that the GQM hydrogel effectively eradicates bacterial biofilms, alleviates inflammation, and reverses alveolar bone resorption, thereby treating periodontitis efficiently. All in all, the GQM hydrogel achieves a synergistic effect of "biofilm disruption–immune metabolic reprogramming" and offers a novel strategy for the reversal of inflammatory bone resorption in periodontitis.

Near-infrared (NIR) fluorescent metal nanodots may have significant advantages in biological detection and bioimaging. Herein, we introduce tunable near-infrared fluorescent gold nanodots (AuNDs) protected by branched polyethylenimine (PEI) modified by surface segmental attachment of sulfhydryl groups (PEI-SH), abbreviated as PEI-SH-AuNDs, for simultaneous gene delivery and cell imaging. The modified PEI endows the resultant PEI-SH-AuNDs with the following excellent advantages. Sulfhydryl groups of PEI-SH anchor to the surface of AuNDs, and such polycations with amine groups give PEI-SH-AuNDs remarkable stability. The cationic polymer PEI-SH with positive charges enables PEI-SH-AuNDs to perform gene delivery, and the gene transfection efficiency can reach 22.8%. Moreover, the fluorescence of PEI-SH-AuNDs is tunable from visible red light (wavelength 609 nm) to NIR light (wavelength 811 nm) via an increase in the size of AuNDs. PEI-SH-AuNDs yielded gene transfection efficiency similar to that of commercial PEI, but showed much lower cytotoxicity and much greater red-shift fluorescence. With excellent photoluminescent properties, such multifunctional fluorescent PEI-SH-AuNDs hold promise in applications to bioimaging and as ideal fluorescent probes for tracking gene transfection behavior.