Boron neutron capture therapy kills cancer cells without harming normal cells

Cancer painfully ends more than 500,000 lives in the United States each year, according to the Centers for Disease Control and Prevention. The scientific crusade against cancer recently achieved a victory under the leadership of University of Missouri Curators’ Professor M. Frederick Hawthorne. Hawthorne’s team has developed a new form of radiation therapy that successfully put cancer into remission in mice. This innovative treatment produced none of the harmful side-effects of conventional chemo and radiation cancer therapies. Clinical trials in humans could begin soon after Hawthorne secures funding.

Cancer cells grow faster than normal cells and in the process absorb more materials than normal cells. Hawthorne’s team took advantage of that fact by getting cancer cells to take in and store a boron chemical designed by Hawthorne. When those boron-infused cancer cells were exposed to neutrons, a subatomic particle, the boron atom shattered and selectively tore apart the cancer cells, sparing neighboring healthy cells.

PNAS – Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

The physical properties of boron made Hawthorne’s technique possible. A particular form of boron will split when it captures a neutron and release lithium, helium and energy. Like pool balls careening around a billiards table, the helium and lithium atoms penetrate the cancer cell and destroy it from the inside without harming the surrounding tissues.

“A wide variety of cancers can be attacked with our BNCT technique,” Hawthorne said. “The technique worked excellently in mice. We are ready to move on to trials in larger animals, then people. However, before we can start treating humans, we will need to build suitable equipment and facilities. When it is built, MU will have the first radiation therapy of this kind in the world.”

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-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 Na3[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 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg 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 × 1012 neutrons per cm2 (±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.

SOURCES – PNAS, University of Missouri

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