Paclitaxel-hyaluronan hydrosoluble bioconjugate: mechanism of action in human bladder cancer cell lines

Urologic Oncology
Isabella Monia MontagnerAntonio Rosato

Abstract

A previously described hydrosoluble paclitaxel-hyaluronan bioconjugate appears particularly well suited for treatment of superficial bladder cancer because of its in vitro cytotoxic profile against urothelial carcinoma (UC) cell lines and in vivo biocompatibility. The aim of this work was to assess the mechanism of action of the bioconjugate in UC cells. Expression of CD44 and RHAMM hyaluronan-binding receptors in RT-4 and RT-112/84 UC cell lines, interaction of fluorochrome-labeled bioconjugate with tumor cells, CD44 modulation upon incubation with the compound or free hyaluronan, and caspase activation were assessed by flow cytometry. Cytotoxicity was studied by the MTT assay. Analysis of bioconjugate intracellular localization and effects on β-tubulin organization was carried out by confocal microscopy. The paclitaxel-hyaluronan bioconjugate bound to UC tumor cells entered intracellular compartments through a saturable and energy-dependent mechanism that involved CD44, as assessed by blocking with specific antibody. Upon internalization, the bioconjugate accumulated into lysosomes where the esteric bond between paclitaxel and the hyaluronan moiety was cleaved, leading to cytoplasmic diffusion of the free drug, caspase activa...Continue Reading

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Citations

Mar 20, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Silvia ArpiccoFranco Dosio
Oct 11, 2015·Journal of Drug Targeting·George MattheolabakisMansoor M Amiji
Dec 15, 2015·Expert Opinion on Drug Delivery·N Vijayakameswara RaoJae Hyung Park
Nov 26, 2015·Advanced Drug Delivery Reviews·Franco DosioElias Fattal
Oct 9, 2015·International Journal of Cell Biology·Suniti MisraShibnath Ghatak
Jun 30, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Isabella Monia MontagnerAntonio Rosato
Feb 7, 2019·The FEBS Journal·Anastasia G TavianatouNikos K Karamanos
Jun 23, 2015·Oncoscience·Isabella Monia MontagnerAntonio Rosato
Apr 10, 2021·Biomaterials·Yachao ZhangShuangying Gui

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