Shno Asad, Alexandra Teleki

Affiliates

Science for Life Laboratory, Department of Pharmacy, Uppsala University, Sweden

Abstract

Background:
The alarming trend of increased incidence and prevalence of patients suffering of inflammatory bowel disease (IBD) has made the condition a highly concerning disorder globally. The challenging and invasive diagnostic procedures makes IBD a problematic condition to detect, particularly for pediatric patients. Our work aims to complement the current diagnostic measures by developing targeted contrast agents for detecting IBD via magnetic resonance imaging (MRI).
Together with gastroenterologists at Uppsala University Hospital and Linköping University, we develop MRI active biosensors for localizing and assessing IBD disease activity in vivo. We engineer superparamagnetic iron oxide nanoparticles (SPIONs) for oral administration to act as MRI contrast agents in the gastrointestinal tract. The nanomaterials are functionalized with antibodies on their surface to target and thereby visualize inflamed intestinal tissue by MRI. Secreted luminal biomarkers, e.g. calprotectin or lipocalin, are targeted by magnetic biosensors for direct in situ quantification of disease activity.

Methods:
SPIONs were synthesized using flame spray pyrolysis. Surface modification with amines followed by linker-conjugation onto SPION surface was achieved through chemical reactions. Cytotoxicity of SPION was evaluated in Caco-2 cells. Cell monolayer integrity was investigated using Lucifer yellow as permeation marker. ICAM-1 protein was identified as a common biomarker in both human cell- and animal models for IBD, which consisted of inflamed Caco-2 cells and DSS-treated mice, respectively.

Results:
Successful amine-functionalization of SPION was confirmed by spectroscopic and thermal methods. The linker was obtained at 94 % yield, confirmed by NMR spectroscopy, and attached onto SPION surface. Cytotoxic effects were not observed in cells exposed to various concentrations of SPIONs (100-500 ug/ml) and did not seem to induce increased permeability in the inflamed cell model either. In our ongoing work, we are coupling the linker-modified SPIONs with antibodies for ICAM-1 and evaluating their targeting capability after oral administration to our in vivo model for IBD.

Conclusions:
Functionalized SPIONs could serve as targeted MRI-contrast agents for IBD. The development of non-invasive and safe biosensors for IBD patients would complement the currently used diagnostic measures.