An Orally Administered CeO₂@Montmorillonite Nanozyme Targets Inflammation for Inflammatory Bowel Disease Therapy

Abstract

Safe, effective, and convenient administration of therapeutic nanomaterials is one of the greatest difficulties in nanomedicine. To tackle this challenge, a system which couples multi-enzyme mimicking CeO 2 nanoparticles with clinically approved montmorillonite (MMT) for inflammatory bowel disease (IBD) therapy is reported. CeO 2 exhibits superoxide dismutase-and catalase-like activities, and hydroxyl radical scavenging activity, making it more efficient at scavenging reactive oxygen species (ROS) than noncatalytic antioxidants while being more stable than free enzymes. In addition, negatively-charged MMT can be orally administered and specifically adsorbed onto positively-charged inflamed colon tissue via electrostatic interactions for targeted delivery. When the two are assembled together by in situ growth of CeO 2 onto MMT, the optimized CeO 2 @MMT(1:9) is stable in the stomach for oral delivery, targets the inflamed colon through electrostatic interactions, and reduces inflammation through ROS scavenging, all without any significant systemic exposure as demonstrated by the relief of murine IBD in vivo.

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications

“…For example, the lack of targeting strategies and the risk of side effects with increasing dosage increased the difficulty in treating inflammatory bowel disease (IBD) [397]. By growing CeO 2 NPs in situ on montmorillonite (MMT) sheets, Zhao et al designed CeO 2 @ MMT nanozymes with SOD-type, CAT-type and • OH scavenging properties to directly target the inflammatory colon for IBD therapy [394]. In this system, MMT alleviated the potential nanotoxicity of CeO 2 NPs via reducing their https://doi.org/10.1007/s40820-021-00674-8 © The authors [396].…”

Reactive-oxygen-species-scavenging nanomaterials for resolving inflammation

“… Materials Working mechanisms Indications Ref. CeO 2 NPs SOD- and CAT-mimetic nanozyme activities Colitis; acute liver injury; stroke therapy; Alzheimer's disease; monocrotaline-induced pulmonary arterial hypertension; diabetic ulcer wounds; Parkinson's disease; rheumatoid arthritis [ 36 , 41 , 45 , [119] , [120] , [121] , [122] , [123] ] Pt NPs POD-, CAT-, and SOD-like nanozyme activities Chronic inflammatory diseases; vascular diseases; cerebral cavernous malformation disease; hepatic ischemia/reperfusion injury [ 50 , [124] , [125] , [126] ] Cu-based NPs POD-, CAT-, SOD-, and glutathione-like enzyme activities Parkinson's disease; kidney and liver injury; inflamed wounds; enteritis and wound healing; caries [ 15 , 56 , 57 , 127 , 128 ] PB NPs POD-, CAT-, and SOD-like multienzyme activities High glucose contents, and oxygen glucose deprivation and reperfusion; acute pancreatitis; dextran sulfate sodium-induced colitis; brain diseases; inflammatory bowel disease [ 16 , [59] , [60] , [61] , [62] ] SOD-containing NPs SOD enzyme activity Brain ischemia–reperfusion injury; colitis; testicular oxidative stress; myocardial ischemia–reperfusion injury; neuroprotective [ 63 , 65 , [129] , [130] , [131] ...…”

“…Copyright 2018, Wiley. (C) Design and synthesis of orally administered CeO 2 @MMT aimed at targeting an inflamed colon during the treatment of inflammatory bowel disease (IBD) [ 36 ]. Copyright 2020, Wiley-VCH Verlag.…”

“…IL-10) levels are significantly upregulated ( Fig. 5 C) [ 36 ]. The suppression of ROS-triggered inflammation by ceria-NP scavenging of ROS can inhibit the translocation of the P65 NF- κ B subunit.…”

Recent Progress in the Diagnosis and Precise Nanocarrier-Mediated Therapy of Inflammatory Bowel Disease

“…Zhao et al designed and synthesized a nanozyme system of CeO 2 @MMT, which is capable of oral administration. 66 The MMT sheets can effectively avoid systemic absorption of CeO 2 and enhance the accumulation of the DDSs in inflamed sites through charge interactions. CeO 2 can impart MMT with anti-ROS capabilities, and thus inflammation can be alleviated.…”