Engineered Macrophage Membrane-Camouflaged Nanodecoys Reshape the Infectious Microenvironment for Efficient Periodontitis Treatment
Sihan Lin, Zeqian Xu, Yulan Liu, Guangzheng Yang, Xuanyu Qi, Yijia Huang, Mingliang Zhou, Xinquan Jiang
Abstract
A vicious cycle between microbiota dysbiosis and hyperactivated inflammation, hardly disrupted by conventional therapies, remains a significant clinical challenge for periodontitis treatment. Herein, by cloaking a cascade catalysis system in an engineered macrophage membrane, a nanodecoy-based strategy, with targeted bacteria-killing and immunomodulatory abilities, is proposed for reshaping the hostile periodontitis microenvironment. Specifically, recombinant human antimicrobial peptide, LL-37, is anchored to a Toll-like receptor-enriched macrophage membrane via genetic engineering, which facilitates the specific bacteria elimination and efficient tissue retention of the nanodecoys. Moreover, the cascade catalysis system integrates L-amino acid oxidase (LAAO) with hollowed manganese dioxide (hMnO 2 ) by reciprocal elevation of the catalytic efficiency of hMnO 2 and LAAO, leading to accelerated O 2 generation under a hypoxic microenvironment and disrupted metabolism of periodontopathogenic bacteria. Notably, the nanodecoys trigger the nuclear translocation of NF-E2-related factor-2 (NRF2) to reduce oxidative stress response and rewire the polarization of macrophages, thereby boosting the osteogenic differentiation of osteoblasts. Furthermore, the alveolar bone regeneration therapeutically benefits from the nanodecoys in vivo. Altogether, these results highlight the attractive functions of engineered macrophage membrane-cloaked nanodecoys for effective periodontitis treatment.