Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, China; Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, China.
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, China; Department of Prosthodontics, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Biomaterials. 2021 Jan;268:120614. doi: 10.1016/j.biomaterials.2020.120614. Epub 2020 Dec 18.
Antibacterial photodynamic therapy (aPDT) is of vital importance for the treatment of periodontal diseases due to its great potential on effective elimination of pathogenic bacteria via overwhelming reactive oxygen species (ROS) generation. However, the excessive ROS after the therapeutic process may impose an oxidative stress within periodontal pockets, consequently leading to an irreversible destroy in surrounding tissue and severely limit its biomedical applications. In this study, considering the contradiction between ROS in bacteriostasis and inflammation, the role of ROS in different temporal and spatial states has been fully studied. Accordingly, we have designed composite nanomaterials that can play ROS based aPDT and anti-inflammatory effect by eliminating ROS, taking account of different ratio of photosensitizer/ROS scavenger to realize a time-sequential manner. Herein, a simple multifunctional nanocomposite was fabricated by coating red light-excited photosensitizer chlorin e6 (Ce6) onto nanoceria, achieving simultaneous sterilization and inflammation elimination via a dual directional regulation effect. This nano-based platform could utilize the aPDT for antibacterial purpose in the first stage with red-light irradiation, and subsequently scavenge the residual ROS via nanoceria to modulate host immunity by down-regulating the M1 polarization (pro-inflammatory) of macrophages and up-regulating the M2 polarization (anti-inflammatory and regenerative) of macrophages. Moreover, the local ROS level induced by activated inflammation pathway can be adjusted in a very long time because of the charge conversion effect of CeO. The regenerative potential of inflammatory surrounding tissues was improved in the animal model. Our strategy will open a new inspiration to fight against the defects of aPDT in the treatment of periodontal disease, even in the anti-infection therapy for the future clinical application.
抗菌光动力疗法（aPDT）对于治疗牙周病至关重要，因为它通过产生大量的活性氧（ROS）来有效消除致病菌具有很大的潜力。然而，治疗过程中产生的过多 ROS 可能会在牙周袋内造成氧化应激，从而导致周围组织的不可逆破坏，并严重限制其在生物医学中的应用。在本研究中，考虑到抑菌和炎症过程中 ROS 的矛盾，充分研究了 ROS 在不同时间和空间状态下的作用。因此，我们设计了复合纳米材料，通过消除 ROS 发挥基于 ROS 的 aPDT 和抗炎作用，考虑到不同的光敏剂/ROS 清除剂的比例以实现时间顺序方式。在这里，通过将红光激发的光敏剂氯代叶绿素 e6（Ce6）涂覆到纳米氧化铈上，制备了一种简单的多功能纳米复合材料，通过双重定向调控作用实现了同时杀菌和消除炎症。该纳米平台可以在第一阶段通过红光照射利用 aPDT 进行抗菌，随后通过纳米氧化铈清除残留的 ROS，通过下调巨噬细胞的 M1 极化（促炎）和上调巨噬细胞的 M2 极化（抗炎和再生）来调节宿主免疫。此外，由于 CeO 的电荷转换效应，激活炎症途径所诱导的局部 ROS 水平可以在很长一段时间内进行调节。在动物模型中，改善了炎症周围组织的再生潜力。我们的策略将为克服 aPDT 在治疗牙周病方面的缺陷开辟新的思路，甚至为未来的抗感染治疗提供新的思路。
