Polydopamine Modified Ceria Nanorods Alleviate Inflammation in Colitis by Scavenging ROS and Regulating Macrophage M2 Polarization

Int J Nanomedicine. 2023 Aug 14:18:4601-4616. doi: 10.2147/IJN.S416049. eCollection 2023.

Abstract

Background: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy.

Methods: CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model.

Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury.

Conclusion: The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.

Keywords: PDA; anti-inflammation; antioxidation; ceria; colitis; macrophage polarization; nanozyme.

MeSH terms

  • Animals
  • Cell Polarity
  • Cerium
  • Colitis* / drug therapy
  • Colitis* / pathology
  • Disease Models, Animal
  • Free Radical Scavengers* / chemistry
  • Free Radical Scavengers* / pharmacology
  • Free Radical Scavengers* / therapeutic use
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Indoles* / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanotubes*
  • Polymers* / chemistry
  • Polymers* / pharmacology
  • Polymers* / therapeutic use
  • RAW 264.7 Cells
  • Reactive Oxygen Species* / metabolism

Substances

  • polydopamine
  • Indoles
  • Polymers
  • Free Radical Scavengers
  • Reactive Oxygen Species
  • ceric oxide
  • Cerium

Grants and funding

This work was funded by the National Natural Sciences Foundation of China (81571800), Jiangsu Provincial Key Research and Development Program (BE2020629), Development of Science and Technology of Nanjing (YKK19094), and “3456” Cultivation Program for Junior Talents of Nanjing Stomatological Hospital, Medical School of Nanjing University (0222R212).