Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy of cancers

Bioconjug Chem. 2013 Jan 16;24(1):124-32. doi: 10.1021/bc300527n. Epub 2012 Dec 19.

Abstract

Mercaptoundecahydrododecaborate (BSH)-encapsulating 10% distearoyl boron lipid (DSBL) liposomes were developed as a boron delivery vehicle for neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in addition to its encapsulated agents. BSH-encapsulating 10% DSBL liposomes have high boron content (B/P ratio: 2.6) that enables us to prepare liposome solution with 5000 ppm boron concentration. BSH-encapsulating 10% DSBL liposomes displayed excellent boron delivery efficacy to tumor: boron concentrations reached 174, 93, and 32 ppm at doses of 50, 30, and 15 mg B/kg, respectively. Magnescope was also encapsulated in the 10% DSBL liposomes and the real-time biodistribution of the Magnescope-encapsulating DSBL liposomes was measured in a living body using MRI. Significant antitumor effect was observed in mice injected with BSH-encapsulating 10% DSBL liposomes even at the dose of 15 mg B/kg; the tumor completely disappeared three weeks after thermal neutron irradiation ((1.5-1.8) × 10(12) neutrons/cm(2)). The current results enabled us to reduce the total dose of liposomes to less than one-fifth compared with that of the BSH-encapsulating liposomes without reducing the efficacy of boron neutron capture therapy (BNCT).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Borohydrides / chemistry*
  • Boron / administration & dosage*
  • Boron / pharmacokinetics
  • Boron / therapeutic use
  • Boron Neutron Capture Therapy / methods*
  • Female
  • Isotopes / administration & dosage
  • Isotopes / pharmacokinetics
  • Isotopes / therapeutic use
  • Lipids / chemistry
  • Liposomes / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / pathology
  • Neoplasms / radiotherapy*
  • Sulfhydryl Compounds / chemistry*

Substances

  • Borohydrides
  • Isotopes
  • Lipids
  • Liposomes
  • Sulfhydryl Compounds
  • mercaptoundecahydrododecaborate
  • Boron