Lin Sihan, Xu Zeqian, Liu Yulan, Yang Guangzheng, Qi Xuanyu, Huang Yijia, Zhou Mingliang, Jiang Xinquan
Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People's Republic of China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, People's Republic of China.
ACS Nano. 2025 Apr 29;19(16):15345-15362. doi: 10.1021/acsnano.4c14305. Epub 2025 Apr 14.
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) by reciprocal elevation of the catalytic efficiency of hMnO and LAAO, leading to accelerated O 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.
微生物群失调与炎症过度激活之间的恶性循环难以被传统疗法打破，仍然是牙周炎治疗面临的重大临床挑战。在此，通过将级联催化系统包裹在工程化巨噬细胞膜中，提出了一种基于纳米诱饵的策略，该策略具有靶向杀菌和免疫调节能力，用于重塑恶劣的牙周炎微环境。具体而言，重组人抗菌肽LL-37通过基因工程锚定在富含Toll样受体的巨噬细胞膜上，这有助于纳米诱饵特异性清除细菌并有效保留在组织中。此外，级联催化系统通过相互提高空心二氧化锰（hMnO）和L-氨基酸氧化酶（LAAO）的催化效率，将LAAO与hMnO整合在一起，导致在缺氧微环境下加速O生成并破坏牙周病原菌的代谢。值得注意的是，纳米诱饵触发核因子E2相关因子2（NRF2）的核转位，以降低氧化应激反应并重新调整巨噬细胞的极化，从而促进成骨细胞的成骨分化。此外，纳米诱饵在体内对牙槽骨再生具有治疗益处。总之，这些结果突出了工程化巨噬细胞膜包裹的纳米诱饵在有效治疗牙周炎方面的诱人功能。
