Toward Point-of-Care Diagnostics to Monitor MMP-9 and TNF-α Levels in Inflammatory Bowel Disease

Abstract

We have investigated the association of matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNF-α) levels with colitis severity using an established IL10-/- mouse model, which reflects the severity of inflammation in humans with inflammatory bowel disease (IBD). We found that MMP-9 and TNF-α correlated with colitis severity. In parallel, we developed assays to detect fecal MMP-9 and serum TNF-α using "cap and release"mesoporous silica nanoparticles (MSNs). MMP-9 peptide substrates as "caps"were attached to dye-loaded MSNs. The introduction of MMP-9 resulted in substrate cleavage and subsequent dye release, which was rapidly detected using a fluorometer. For TNF-α, an anti-TNF antibody was used as the "cap". The introduction of TNF-α antigen leads to the release of the dyes because the antigen binds more strongly to the antibody cap. The MSN-based assays can detect MMP-9 and TNF-α effectively, although signal amplification is required to meet clinical sensitivity.