Meccanismo d'azione del bioconiugato idrosolubile paclitaxel-acido ialuronico su linee cellulari umane di tumore della vescica

Translated title of the contribution: [Autom. eng. transl.] Mechanism of action of the water-soluble paclitaxel-hyaluronic acid bioconjugate on human bladder cancer cell lines

Pierfrancesco Bassi, Marco Racioppi, Andrea Volpe, Daniele D'Agostino, B A., I Montagner, B D., R D., C M., Z P., R. A.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

[Autom. eng. transl.] Objectives The paclitaxel-hyaluronic acid bioconjugate is a promising drug for the treatment of recurrent non-invasive bladder muscle neoplasia, both for its biocompatibility and for the results obtained in the recent phase 1-2 study against in-responsive bladder carcinoma in situ . The activity of paclitaxel-hyaluronic acid bioconjugate was evaluated after the results obtained on cell lines. Materials and methods Through flow cytometry the expression of CD 44 and RHAMM hyaluronan-binding receptors was identified in human RT -4 and RT-112/84 cell lines; the interaction of the bioconjugate with tumor cells and the modulation of CD 44 expression after its passage through the cell membrane, both of the compound and of the hyaluronate alone, was also evaluated. The analysis of the intracellular localization of the bioconjugate and the effects on the beta-tubulin organization were evaluated with confocal microscopy. Results The paclitaxel-hyaluronic acid bioconjugate binds to transitional bladder tumor cells, modulates the expression of CD 44 and penetrates into cells through a saturation mechanism that does not involve the RHAMM hyaluronana-binding receptors, as these latter they are expressed only at the intracellular level. Discussion After entering the cell, the bioconjugate is internalized inside the lysosomes, where the ester bond between paclitaxel and hyaluronic acid is broken, leading to the intracytoplasmic diffusion of the free drug which, in turn, interacting with beta tubulin leads to disintegration of the microtubule network resulting in cell death. Conclusions The paclitaxel-hyaluronic acid bioconjugate appears to be a new chemical reality characterized by a high affinity for plasma membrane receptors and a mechanism of receptor-mediated endocytosis with subsequent accumulation within the lysosomes. Finally the active molecule is released completely inside the cell thus preserving the cytotoxic potential and the pharmacological activity of paclitaxel alone.
Translated title of the contribution[Autom. eng. transl.] Mechanism of action of the water-soluble paclitaxel-hyaluronic acid bioconjugate on human bladder cancer cell lines
Original languageItalian
Title of host publicationLibro abstract dell' 84° congresso SIU, 23 - 26 Ottobre 2011, Roma
Pages99-100
Number of pages2
Publication statusPublished - 2011
Event84° congresso SIU - Roma
Duration: 23 Oct 201126 Oct 2011

Conference

Conference84° congresso SIU
CityRoma
Period23/10/1126/10/11

Keywords

  • PACLITAXEL-ACIDO IALURONICO
  • TUMORE VESCICA

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