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

We have investigated the association of matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor alpha (TNF-alpha) 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-alpha correlated with colitis severity. In parallel, we developed assays to detect fecal MMP-9 and serum TNF-alpha 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-alpha, an anti-TNF antibody was used as the cap. The introduction of TNF-alpha 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-alpha effectively, although signal amplification is required to meet clinical sensitivity.

Automated summary

The association of MMP-9 and TNF-alpha levels with colitis severity was investigated using an established IL10-/- mouse model. Assays using cap and release mesoporous silica nanoparticles were developed to detect fecal MMP-9 and serum TNF-alpha. The assays effectively detected MMP-9 and TNF-alpha, but signal amplification is needed for clinical sensitivity.