Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma

Anticancer Res. 2016 Mar;36(3):907-11.

Abstract

Background: Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells.

Materials and methods: In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model.

Results: HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT.

Conclusion: Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM.

Keywords: BNCT; BSH; CD44; HA; MPM; hyaluronan formulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron Neutron Capture Therapy / methods*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / pharmacology
  • Mesothelioma / mortality
  • Mesothelioma / therapy*
  • Mice
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiation-Sensitizing Agents / pharmacology
  • Survival Analysis
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Radiation-Sensitizing Agents
  • Hyaluronic Acid