title: Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.
abstract: The polyhedral borane ion [n-B20H18]2- reacts with liquid ammonia in the presence of a suitable base to produce an apical-equatorial (ae) isomer of the [B20H17NH3]3- ion, [1-(2'-B10H9)-2-NH3B10H8]3-. The structure of this product has been confirmed by 11B NMR spectroscopy and x-ray crystallography. This species undergoes acid-catalyzed rearrangement to an apical-apical (a2) isomer, [1-(1'-B10H9)-2-NH3B10H8]3-, whose structure has been determined by 11B NMR spectroscopy. The sodium salts of both the ae and the a2 isomers of [B20H17NH3]3- have been encapsulated within small unilamellar liposomes, composed of distearoyl phosphatidylcholine/cholesterol (1:1), and investigated as boron-delivery agents for boron neutron capture therapy (BNCT) of cancer. The biodistribution of boron was determined after the injection of liposomal suspensions into BALB/c mice bearing EMT6 tumors. Both [B20H17NH3]3- isomers exhibited excellent tumor uptake and selectivity at very low injected doses, achieving peak tumor boron concentrations of 30-40 micrograms of B/g of tissue and tumor/blood boron ratios of approximately 5. The enhanced retention of the [B20H17NH3]3- isomers by EMT6 tumors may be attributed to their facile intracellular oxidation to an extremely reactive NH3-substituted [n-B20H18]2- ion, the electrophilic [B20H17NH3]- ion. Both isomers of [B20H17NH3]3- are at least 0.5 V more easily oxidized than other previously investigated species containing 20 boron atoms. In another experiment, [ae-B20H17NH3]3- was encapsulated in liposomes prepared with 5% PEG-2000-distearoyl phosphatidylethanolamine in the liposome membrane. As expected, these liposomes exhibited a longer circulation lifetime in the biodistribution experiment, resulting in the continued accumulation of boron in the tumor over the entire 48-hr experiment and reaching a maximum of 47 micrograms of B/g of tumor.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.
authors.forename: D A
authors.initials: DA
authors.lastname: Feakes
authors.forename: K
authors.initials: K
authors.lastname: Shelly
authors.forename: C B
authors.initials: CB
authors.lastname: Knobler
authors.forename: M F
authors.initials: MF
authors.lastname: Hawthorne
mesh_terms: D000818:Animals; D001880:Boranes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D005260:Female; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010084:Oxidation-Reduction; D014018:Tissue Distribution
chemical_list: D001880:Boranes; D008081:Liposomes