Bioengineered Lipid Droplets Enable Synergistic Mitochondria-Targeted Periodontitis Therapy

This study engineers biomimetic lipid droplet-based nanotherapeutics that integrate antimicrobial and mitochondrial repair functions, overcoming the limitations of conventional periodontitis therapies in achieving simultaneous antibacterial, anti-inflammatory, and tissue-reparative effects. In LPS-stimulated RAW264.7, CRAMP was recruited onto LDs, confirmed by IF and WB. GA loading efficiency (UV-Vis) and cytotoxicity (CCK-8) were assessed over 24–72 h. The diameter, zeta potential of GA@LDs-CRAMP were characterized via DLS. Bacterial inhibition against Aa and Pg was quantified via CFU. Mitochondrial repairing was validated using confocal (JC-1, MitoTracker) and DCFH-DA in MGFs. Inflammatory cytokines (IL-6, TNF-α, iNOS, Arg1) and Nrf2 pathway activation (RNA-seq) were quantified via qPCR in BMDMs. In vivo experiments employed 8-week-old male C57BL/6 mice (approved by the Ethics Committee). Periodontitis was induced by ligature placement for 14 days. Nanoparticles were administered locally every 3 days. Maxillae were analyzed by micro-CT and H&E, Masson staining. Inflammatory indicators were quantified via IHC. Statistical significance (p<0.05) was determined by ANOVA. GA@LDs-CRAMP nanoparticles suppress periodontopathogens, repair mitochondria via ROS scavenging, inhibit inflammation through Nrf2 pathway activation, polarize macrophages to M2 phenotypes, and attenuate alveolar bone loss in murine periodontitis models. Bioengineered GA@LDs-CRAMP nanoparticles achieve multimodal periodontitis therapy through mitochondrial repair, anti-inflammatory action, and bone protection, leveraging endogenous lipid droplets to establish targeted nanomedicine and marking a breakthrough in precision treatment of inflammatory oral diseases.