A versatile nanocomposite based on nanoceria for antibacterial enhancement and protection from aPDT-aggravated inflammation via modulation of macrophage polarization

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 CeO2. 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.