International Journal of Nanomedicine (Nov 2022)
Functionalized Prussian Blue Nanozyme as Dual-Responsive Drug Therapeutic Nanoplatform Against Maxillofacial Infection via Macrophage Polarization
Abstract
Junlong Da,1 Ying Li,1 Kai Zhang,1 Junyu Ren,1 Jianqun Wang,1 Xinpeng Liu,1 Xiaoyao Liu,2 Jiahui Zhang,1 Lixue Liu,1 Wenxuan Zhang,1 Shujian Zhang,1 Yuyao Guo,1 Bin Zhang,1,3 Han Jin1 1Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Orthodontics, the First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Heilongjiang Academy of Medical Sciences, Harbin, People’s Republic of ChinaCorrespondence: Han Jin; Bin Zhang, Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China, Tel/Fax +86 0451-86297231, Email [email protected]; [email protected]: Maxillofacial infection is a common disease in stomatology and is difficult to treat owing to its high potential to spread to vital anatomical structures. Excessive levels of reactive oxygen species (ROS) in infected tissues lead to cellular damage and impede tissue regeneration. However, uncontrollable strategies to remove ROS have limited therapeutic efficacy. Nanoparticle systems for scavenging ROS and remodeling the inflammatory microenvironment offer much promise in the treatment of maxillofacial inflammation.Methods: Here, a novel microenvironment-stimuli-responsive drug delivery nanoplatform (HMPB@Cur@PDA) based on a polydopamine (PDA)-functionalized hollow mesoporous Prussian blue (HMPB) nanozyme was developed for the delivery of curcumin (Cur) in the treatment of maxillofacial infection. Low pH and excess ROS in the inflammatory microenvironment cause degradation of the outer PDA layer of the nanocomplex, exposing the HMPB nanozyme and loaded Cur, which synergistically act as a ROS scavenger and anti-inflammatory agent, respectively, and induce macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype.Results: Experiments in vitro provided strong evidence for the application of novel nanocomplexes in scavenging multiple ROS and inhibiting lipopolysaccharide-induced inflammation. In addition, in vivo results obtained using a mouse maxillofacial infection model demonstrated that HMPB@Cur@PDA had excellent biocompatibility, significantly attenuated the inflammatory response in periodontal tissue, and improved the repair of damaged tissue.Conclusion: Our results indicate that HMPB@Cur@PDA nanocomposites have great potential for ROS regulation as well as having anti-inflammatory effects, providing new insights for the development of dual-response maxillofacial infection treatments.Keywords: maxillofacial infection, Prussian blue, nanozyme, polydopamine, reactive oxygen species, macrophage polarization
