Rectal delivery of Zr-labeled infliximab-loaded nanoparticles enables PET imaging-guided localized therapy of inflammatory bowel disease

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2023-12, Vol.11 (47), p.11228-11234
• Main Authors: Fan, Yeli, Wang, Xinyu, Yan, Ge, Gao, Hongfang, Yang, Min
• Format: Article
• Language: English
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d3tb02128a

Inflammatory bowel diseases (IBDs) like Crohn's disease and ulcerative colitis involve chronic gastrointestinal inflammation. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) drives IBD pathogenesis. Anti-TNF-α therapies using monoclonal antibodies (mAbs) like infliximab (INF) help treat IBD but have limitations. We developed inflammation-targeting polyphenol-poloxamer nanoparticles loaded with the anti-inflammatory mAb INF (INF@PPNP) as a novel IBD therapy. Characterization showed that INF@PPNP had favorable stability and purity. Radiolabeling INF@PPNP with 89 Zr enabled tracking localization with positron emission tomography (PET) imaging. Rectal administration of 89 Zr-INF@PPNP led to colon delivery with remarkably reduced systemic exposure versus intravenous INF revealed by non-invasive PET imaging. 89 Zr-INF@PPNP retention at inflamed foci indicated prolonged INF@PPNP action. INF@PPNP rectally achieved similar anti-inflammatory effects as intravenously injected INF, demonstrating the high therapeutic potential. Our findings support the use of nanoparticle-based rectal administration for localized drug delivery, prolonging drug activity and minimizing systemic exposure, ultimately offering an effective approach for treating IBD. Rectal delivery of radiolabeled infliximab nanoparticles enabled PET imaging confirmation of colon targeting and prolonged retention at inflammation sites, while demonstrating comparable anti-inflammatory efficacy to intravenous antibody therapy.