Facile synthesis of dendrimer like mesoporous silica nanoparticles to enhance targeted delivery of interleukin-22. (28th October 2021)

• Record Type: Journal Article
• Authors: Elshaer, Dana; Moniruzzaman, Md.; Ong, Yi Theng; Qu, Zhi; Schreiber, Veronika; Begun, Jakob; Popat, Amirali
• Is Part Of: Biomaterials science. Volume 9:Number 22(2021)
• Page Start: 7402
• Page End: 7411
• Publication Date: 2021-10-28
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm01352a
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Interleukin (IL)-22 is a multifunctional cytokine with a very short half-life that activates STAT3 and can elicit an anti-inflammatory response. We show encapsulation of IL-22 in LPMSN enhances its biological activity and stability in in vitro and human colonic organoids. Abstract : Interleukin (IL)-22 is a multifunctional cytokine with a very short half-life that activates STAT3 and can elicit strong anti-inflammatory effects in the intestine but can induce inflammation in other sites. Several long-circulating IL-22 fusion proteins have been manufactured to date; however, those were associated with adverse effects in other organs limiting their utility for treating intestinal inflammation. Targeted delivery of IL-22 to the intestine could utilize its anti-inflammatory properties and overcome systemic toxicity. Therefore, this study aimed to synthesise large pore mesoporous silica nanoparticles (LPMSN), load recombinant (r)IL-22 in the LPMSN and test its bioactivity in the STAT3 reporter LS174T, wild type LS174T, Caco-2 intestinal epithelial cells, and healthy human colonic organoids. Our data showed one hundred percent loading capacity (w/w) of the synthesised LPMSN, which prolonged IL-22 induced STAT3 luciferase activities in LS174T and p-STAT3 immunofluorescence in Caco-2 cells. LPMSN also stabilized and increased the permeability of rIL-22 across Caco-2 monolayers. Moreover, LPMSN-IL-22 retained the functionality of the cytokine in human colonic organoids. Taken together, these data demonstrate the protection and effective delivery of IL-22 using bio-nanomaterials (LPMSN) that could enable targeted oral delivery of this IL-22.