Schumann, M. | bioRxiv Science

bioRxiv2023

Osteopontin in colitis-associated carcinoma

Patients with ulcerative colitis (UC) and Crohns disease (CD) face a lifelong risk of developing colitis-associated carcinoma (CAC). Current insights into CAC development originate from murine CAC models, while human CAC studies primarily focus on mutational analysis of patient samples. Although the mutational landscape reveals distinct patterns and frequencies compared to colorectal cancer, it falls short in elucidating the inflammatory mechanisms of CAC development. Consequently, we adopted a multi-omics approach to unravel CAC carcinogenesis from an immunological perspective. Our data revealed a robust upregulation of SPP1 gene in CAC at both RNA and protein levels, expressed by CD68+ macrophages. In vitro OPN stimulation demonstrated no direct effect on intestinal epithelial organoids. However, the mutually exclusive spatial location of SPP1/OPN+ macrophages and CD8+ T cells suggests a crucial indirect role of SPP1/OPN in mediating an immunosuppressive tumour microenvironment.

cancer biology↗

bioRxiv2021

Selective uptake into inflamed human intestinal tissue and immune cell targeting by wormlike polymer micelles

Over the 21st century, inflammatory bowel disease (IBD) has become a global disease with no causal therapeutic options. Selective targeting of inflamed areas in the gastrointestinal tract could be an effective treatment circumventing severe side effects for healthy tissue. Our study demonstrates that the shape of polymeric nanostructures represents so far rarely addressed key to required tissue selectivity in the intestine. Ex vivo experiments on human colonic biopsies revealed that crosslinked wormlike micelles featuring a dense poly(ethylene oxide) (PEO) shell exclusively enter the inflamed human mucosa without affecting healthy tissue. Similarly designed spherical micelles ([~]25 nm) or vesicles ([~]120 nm) penetrate both tissues or were barely uptaken at all, respectively. Moreover, it was found that the particles colocalize with immune cells in the lamina propria facilitating a specific targeting of the main pro-inflammatory cells within the diseased human mucosa. These findings demonstrate an untapped potential in particle design and enable new vistas for an effective treatment of IBD.

physiology↗