title: Hyaluronan as carrier of carboranes for tumor targeting in boron neutron capture therapy.
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.
authors.affiliation: Department of Chemistry, University of Rome, La Sapienza, P. le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Chiara Di
authors.initials: CD
authors.lastname: Meo
authors.forename: Luigi
authors.initials: L
authors.lastname: Panza
authors.forename: Donatella
authors.initials: D
authors.lastname: Capitani
authors.forename: Luisa
authors.initials: L
authors.lastname: Mannina
authors.forename: Alessandra
authors.initials: A
authors.lastname: Banzato
authors.forename: Maria
authors.initials: M
authors.lastname: Rondina
authors.forename: Davide
authors.initials: D
authors.lastname: Renier
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Vittorio
authors.initials: V
authors.lastname: Crescenzi
mesh_terms: D001896:Boron Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy*; D012995:Solubility
chemical_list: D001896:Boron Compounds; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid