Bioinspired nanomicelles with octopus-like adhesion for microenvironmental reprogramming in periodontitis.

Periodontitis is a multifactorial disease characterized by bacterial infection, inflammation, oxidative stress, and dysregulated bone remodeling, for which current treatments remain limited. Effective treatment requires not only antimicrobial action but also coordinated modulation of immune and regenerative pathways within the periodontal microenvironment. Here, this study reports a bioinspired "octopus-like" nanomicelle platform with mucoadhesive tentacles and immune-targeting surfaces, designed to enhance drug retention, selective delivery, and multifunctional therapeutic performance. Phenylboronic acid modification enables high-affinity binding to sialic acids in mucosal glycoproteins, prolonging local retention, while fucoidan decoration directs nanomicelles to scavenger receptors on macrophages and neutrophils, the key effector cells in periodontitis. As cannabidiol was used as a potential therapeutic payload, the nanomicelles exhibited potent antibacterial activity against Staphylococcus aureus and Porphyromonas gingivalis, immune microenvironment remodeling and enhanced osteogenic differentiation in vivo. This dual-targeting strategy suppresses macrophage inflammation and oxidative stress via modulating Toll-like receptor, janus kinase-signal transducer and activator of transcription (JAK-STAT), and advanced glycation end products-Receptor for AGEs (AGE-RAGE) pathways, while also reducing neutrophil extracellular traps formation via regulation of apoptosis, mitochondrial depolarization, and calcium signaling. In a mouse periodontitis model, the platform achieved superior therapeutic outcomes compared to free drug. Together, this multifunctional adhesive nanoplatform integrates mucoadhesion, immune modulation, antimicrobial activity, and bone regeneration, offering a versatile and generalizable strategy for periodontitis therapy and broader microenvironmental reprogramming in chronic inflammatory diseases.