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• W1999414270 abstract "A unique structural and functional configuration renders the human urothelium, one of the hardest to overcome biological barriers, and accounts for critical shortcomings in the adjuvant localized therapy of bladder cancer and other severe medical conditions. Strategies to improve intravesical drug absorption are urgently sought, but so far have hardly adopted biorecognitive delivery vectors that are more specifically tailored to the natural characteristics of the target site. The efficient cytoinvasion of uropathogenic bacteria, mediated via a mannose-directed FimH lectin adhesin, and malignancy-dependent differences in bladder cell glycosylation point to considerable unrealized potential of lectins as targeting vectors on the molecular/functional and recognitive level. Here, we outline the ability of wheat germ agglutinin (WGA) to induce endocytosis of conjugated payload in human urothelial SV-HUC-1 cells after stable adhesion to internalizing receptors. A panel of model bioconjugates was prepared by covalently coupling one to six WGA units to fluorescein-labeled bovine serum albumin (fBSA). Cytoadhesive capacity was found to directly correlate to the degree of modification up to a critical threshold of on average three targeting ligands per conjugate. The highly specific, glycan-triggered interaction proved essential for endosomal sorting and was followed by rapid (<60 min) and extensive (>40%) internalization. fBSA/WGA bioconjugates were processed analogously to the free lectin, irrespective of the significantly higher molecular weight (100–300 kD). Durable entrapment of conjugates in acidic, perinuclear compartments without kiss-and-run recycling to the plasma membrane was found in both single cells and monolayers. Our results assign promising potential to glycotargeted delivery concepts in the intravesical setting and offer new perspectives for the application of complex biologicals in the urinary tract." @default.
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• W1999414270 date "2012-10-01" @default.
• W1999414270 modified "2023-10-12" @default.
• W1999414270 title "Lectin bioconjugates trigger urothelial cytoinvasion – A glycotargeted approach for improved intravesical drug delivery" @default.
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• W1999414270 doi "https://doi.org/10.1016/j.ejpb.2012.07.016" @default.
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