Xiao Leyi, Feng Mengge, Chen Chen, Xiao Qi, Cui Yu, Zhang Yufeng
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
Medical Research Institute School of Medicine, Wuhan University, Wuhan, 430071, P. R. China.
Adv Mater. 2023 Oct 24:e2304982. doi: 10.1002/adma.202304982.
The oral cavity comprises an environment full of microorganisms. Dysregulation of this microbial-cellular microenvironment will lead to a series of oral diseases, such as implant-associated infection caused by Staphylococcus aureus (S. aureus) biofilms and periodontitis initiated by Streptococcus oralis (S. oralis). In this study, a liposome-encapsulated indocyanine green (ICG) and rapamycin drug-delivery nanoparticle (ICG-rapamycin) is designed to treat and prevent two typical biofilm-induced oral diseases by regulating the microbial-cellular microenvironment. ICG-rapamycin elevates the reactive oxygen species (ROS) and temperature levels to facilitate photodynamic and photothermal mechanisms under near-infrared (NIR) laser irradiation for anti-bacteria. In addition, it prevents biofilm formation by promoting bacterial motility with increasing the ATP levels. The nanoparticles modulate the microbial-cellular interaction to reduce cellular inflammation and enhance bacterial clearance, which includes promoting the M2 polarization of macrophages, upregulating the anti-inflammatory factor TGF-β, and enhancing the bacterial phagocytosis of macrophages. Based on these findings, ICG-rapamycin is applied to implant-infected and periodontitis animal models to confirm the effects in vivo. This study demonstrates that ICG-rapamycin can treat and prevent biofilm-induced oral diseases by regulating the microbial-cellular microenvironment, thus providing a promising strategy for future clinical applications.
口腔是一个充满微生物的环境。这种微生物 - 细胞微环境的失调会导致一系列口腔疾病，例如由金黄色葡萄球菌（S. aureus）生物膜引起的种植体相关感染以及由口腔链球菌（S. oralis）引发的牙周炎。在本研究中，设计了一种脂质体包裹的吲哚菁绿（ICG）和雷帕霉素药物递送纳米颗粒（ICG - 雷帕霉素），旨在通过调节微生物 - 细胞微环境来治疗和预防两种典型的生物膜诱导性口腔疾病。ICG - 雷帕霉素可提高活性氧（ROS）水平和温度，以便在近红外（NIR）激光照射下促进光动力和光热机制来抗菌。此外，它通过提高ATP水平促进细菌运动来防止生物膜形成。这些纳米颗粒调节微生物 - 细胞相互作用，以减少细胞炎症并增强细菌清除，这包括促进巨噬细胞的M2极化、上调抗炎因子转化生长因子 -β（TGF -β）以及增强巨噬细胞对细菌的吞噬作用。基于这些发现，将ICG - 雷帕霉素应用于种植体感染和牙周炎动物模型以证实其体内效果。本研究表明，ICG - 雷帕霉素可通过调节微生物 - 细胞微环境来治疗和预防生物膜诱导性口腔疾病，从而为未来的临床应用提供了一种有前景的策略。
