期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 16, 页码 6512-6517出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1303437110
关键词
oncology; radiation; cancer; nanoparticles
资金
- US Department of Energy [DE-FG03-95ER61975]
- National Institutes of Health [R01CA097342]
The application of boron neutron capture therapy (BNCT) following liposomal delivery of a B-10-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na-3[1-(2'-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)(15)-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 mu g/g tumor at 54 h-with tumor/blood boron ratios being greatest at 96 h (5.68: 1; 43 mu g boron/g tumor)-following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 x 10(12) neutrons per cm(2) (+/- 7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study.
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