Facile synthesis of dendrimer like mesoporous silica nanoparticles to enhance targeted delivery of interleukin-22.

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.