Synthetic Polymer Nanoparticles Conjugated with FimH_A from E. coli Pili to Emulate the Bacterial Mode of Epithelial Internalization

Abstract

Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic Escherichia coli type 1 pilus adhesin FimHA through amidation chemistry to enable bladder epithelial cell binding and internalization of the nanoparticles in vitro.

Urinary Tract Infection: Pathogenesis and Outlook

“…, Yersinia pestis ). Direct application to the bladder luminal surface of nanoparticles, perhaps coated with the FimH adhesin [85], has also been explored in mice as a means to accomplish targeted delivery of novel therapeutics to the host [86]. …”

Morphologic Design of Silver-Bearing Sugar-Based Polymer Nanoparticles for Uroepithelial Cell Binding and Antimicrobial Delivery

“…Flow cytometry and fluorescent confocal microscopy characterizations were carried out on the fluorescently labeled NPs derived from dye-PDGC­(cys) 70 - b -PLLA 18 , dye-PDGC­(cys) 47 - b -PLLA 44 , and dye-PDGC­(cys) 39 - b -PLLA 74 to quantitatively determine their association with uroepithelial cells and visualize internalization, respectively. Cultured uroepithelial cells, either as subconfluent adherent cells or in suspension, were treated with MB 488-labeled NPs of various morphologies, using concentrations and exposure times established in our prior work . Cellular association with NPs was quantified by flow cytometry, and internalization was observed qualitatively by confocal fluorescence microscopy after cell-surface staining with AlexaFluor 594-labeled wheat germ agglutinin (WGA).…”

“…Previous work demonstrated that shell cross-linked knedel-like (SCK) spherical NPs having dimensions of ca . 20–40 nm and functionalized with E. coli FimH A , the type 1 pilus tip adhesin that mediates bacterial attachment to bladder epithelium, readily bound cultured uroepithelial cells but were rarely internalized. , This result indicated that, despite specific interactions between NPs and cell-surface receptors, achieving epithelial internalization of NPs would require more than merely installing a targeting ligand. A logical next approach relies on the optimization of NP size and shape to promote multivalent cell binding and improve internalization. , …”

Bioadhesive Bacterial Microswimmers for Targeted Drug Delivery in the Urinary and Gastrointestinal Tracts

“…Specific eukaryotic cells express mannose on their cell membranes. Pathogenic E. coli strains use a lectin–mannose attachment and some other virulence factors to colonize cells in intestinal and urinary tract . We showed that the bacteriabots that were fabricated from E. coli MG1655 (having pili) have the competence to become immobilized on mannose‐functionalized surfaces.…”