Functionalized Prussian Blue Nanozyme as Dual-Responsive Drug Therapeutic Nanoplatform Against Maxillofacial Infection via Macrophage Polarization

Int J Nanomedicine. 2022 Nov 30:17:5851-5868. doi: 10.2147/IJN.S385899. eCollection 2022.

Abstract

Purpose: 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: Prussian blue; macrophage polarization; maxillofacial infection; nanozyme; polydopamine; reactive oxygen species.

MeSH terms

  • Anti-Inflammatory Agents*
  • Macrophages*
  • Pharmaceutical Preparations

Substances

  • ferric ferrocyanide
  • Pharmaceutical Preparations
  • Anti-Inflammatory Agents

Grants and funding

This work was supported by National Natural Science Foundation of China (Grant Nos. 81870736, 81801040, 81500816, 81570951) and the Natural Science Foundation of Heilongjiang Province of China (Grant No. YQ2020H018, LH2020H057).