Hyaluronan as carrier of carboranes for tumor targeting in boron neutron capture therapy

Chiara Di Meo, Luigi Panza, Donatella Capitani, Luisa Mannina, Alessandra Banzato, Maria Rondina, Davide Renier, Antonio Rosato, Vittorio Crescenzi

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Boron neutron capture therapy (BNCT) represents a promising approach for tumor therapy. A critical requirement for BNCT is tumor targeting, a goal that is currently addressed with the development of low and high molecular weight agents capable of interacting with receptors expressed by cancer cells. Here, we describe a new bioconjugate (HApCB) composed by n-propyl carborane linked to hyaluronan (HA) via an ester linkage for a degree of substitution of approximately 30%, leading to a water-soluble derivative. The structure and main physicochemical characteristics of the new HA derivative were determined by means of Fourier transform infrared, fluorescence, and 1H, 13C, and 10B NMR analysis and are herein reported in detail. As HA is recognized by the CD44 antigen, densely populating the surface of many tumor cells, HApCB is expected to deliver boron atoms from the locally released carborane cages directly to target cells for antitumor application in BNCT. In vitro biological experiments showed that HApCB was not toxic for a variety of human tumor cells of different histotypes, specifically interacted with CD44 as the native unconjugated HA, and underwent uptake by tumor cells, leading to accumulation of amounts of boron atoms largely exceeding those required for a successful BNCT approach. Thus, HApCB may be regarded as a promising new BNCT agent for specific targeting of cancer cells overexpressing the CD44 receptor.

Lingua originaleInglese
pagine (da-a)552-559
Numero di pagine8
RivistaBiomacromolecules
Volume8
Numero di pubblicazione2
DOI
Stato di pubblicazionePubblicato - feb 2007

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