Yao Wan

Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to inhibit M1 polarization of macrophages by the favorable ability of reactive oxygen species (ROS) scavenging. However, the function of nanoceria on macrophage polarization toward M2 phenotype (anti-inflammation) in reparative phase of periodontal inflammation is quite limited. In this work, by introducing an antioxidant drug quercetin onto nano-octahedral ceria, synergistic and intense regulation of host immunity against periodontal disease is realized. Such nanocomposite can control the phenotypic switch of macrophages by not only inhibition of M1 polarization for suppressing the damage in the destructive phase but also promotion of M2 polarization for regenerating the surrounding tissues in reparative phase of periodontal disease. As-prepared nanocomposite can effectively increase the M2/M1 ratio of macrophage polarization in inflammatory cellular models by lipopolysaccharide stimulation. More importantly, the nanocomposite also exerts an improved therapeutic potential against local inflammation by significant downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines in an animal model with periodontal inflammation. Therefore, this newly developed nanomedicine is efficient in ROS scavenging and driving pro-inflammatory macrophages to the anti-inflammatory phenotype to eliminate inflammation, thereby providing a promising candidate for treating periodontal inflammation.

Abstract Numerous nanomedicines currently emerge to reduce the dramatic threat in antibiotics resistance for antibacterial application against severe bacterial infections, while it is restricted by over‐reacted immune response to pathogenic bacteria. Herein, enzymatic activity is introduced into the zeolitic imidazolate framework‐8 (ZIF‐8) to achieve sterilization by releasing Zn ions, as well as inflammation regulation through the variable valence of Mn ions that are uniformly doped into its framework. Within this simple metal organic framework (MOF) structure design, Mn‐ZIF‐8 possesses the co‐existence of Mn 2+ /Mn 4+ to endow the nanocomposite with the anti‐inflammatory capabilities, which can be adjusted through the redox environment. The enzymatic activity of Mn ions and superiority of pore structure of ZIF‐8 are effectively combined to realize the substrate selection via reactant molecular size and high‐efficiency internal catalytic performance. By such design, this nanocomposite would not only exhibit an excellent antibacterial performance against pathogenic bacteria, but also reshape the inflammatory immunity by regulating macrophage polarization to suppress over‐reacted inflammation, leading to a favorably therapeutic efficiency on bacteria‐infected wound healing in animal models. Taken together, this nanoplatform provides effective approach for accelerating infected wound healing via bacteria killing and inflammation modulation, and may be extended for the therapy of other severe bacteria‐induced infections.

Abstract The hypoxic microenvironment, continuous oxygen consumption, and poor excitation light penetration depth during antimicrobial photodynamic therapy (aPDT) tremendously hinder the effects on bacterial inactivation. Herein, a smart nanocomposite with oxygen‐self‐generation is presented for enhanced and selective antibacterial properties against anaerobe‐induced periodontal diseases. By encapsulating Fe 3 O 4 nanoparticles, Chlorin e6 and Coumarin 6 in the amphiphilic silane, combined light (red and infrared) stimulated aPDT is realized due to the increased conjugate structure, the corresponding red‐shifted absorption, and the magnetic navigation performance. To address the hypoxic microenvironment problem, further modification of MnO 2 nanolayer on the composites is carried out, and catalytical activity is involved for the decomposition of hydrogen peroxide produced in the metabolic processing, providing sufficient oxygen for aPDT in infection sites. Experiments in the cellular level and animal model proved that the rising oxygen content could effectively relieve the hypoxia in a periodontal pocket and enhance the ROS production, remarkably boosting aPDT efficacy. The increasing local level of oxygen also shows the selective inhibition of pathogenic and anaerobic bacteria, which determines the success of periodontitis treatment. Therefore, this finding is promising for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria‐induced infections, for future clinical application.

The heavy burden of oral diseases such as oral cancers, dental caries, periodontitis, etc. and their consequence on the patient's quality of life demonstrated an urgent demand for developing effective therapeutics. Quercetin as a natural derived flavonoid, could be utilized in the therapeutic formulation of various diseases such as diabetes, breast cancer and asthma, owing to its prominent pharmacological values. In the last decade, the applications of quercetin as a natural compound in oral treatment have attracted increasing interest due to its multifunction including antioxidant, antibacterial, anti-inflammatory and antineoplastic activities. Besides, considering the low bioavailability of quercetin, great efforts have been made in its drug delivery systems to address the problem of limited application. Therefore, this review summarized the cutting-edge researches on versatile effects and enhanced bioavailability of quercetin resulting from innovative drug delivery systems, particularly focused on its potential against oral diseases. The application of quercetin would provide novel and promising therapeutic approach for clinical treatment, promoting the development of global dental public health.