Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors.

Journal Article (Journal Article)

Histone deacetylase inhibitors (HDACIs) represent a class of promising agents that can improve radiotherapy in cancer treatment. However, the full therapeutic potential of HDACIs as radiosensitizers has been restricted by limited efficacy in solid malignancies. In this study, we report the development of nanoparticle (NP) formulations of HDACIs that overcome these limitations, illustrating their utility to improve the therapeutic ratio of the clinically established first generation HDACI vorinostat and a novel second generation HDACI quisinostat. We demonstrate that NP HDACIs are potent radiosensitizers in vitro and are more effective as radiosensitizers than small molecule HDACIs in vivo using mouse xenograft models of colorectal and prostate carcinomas. We found that NP HDACIs enhance the response of tumor cells to radiation through the prolongation of γ-H2AX foci. Our work illustrates an effective method for improving cancer radiotherapy treatment.

Full Text

Duke Authors

Cited Authors

  • Wang, EC; Min, Y; Palm, RC; Fiordalisi, JJ; Wagner, KT; Hyder, N; Cox, AD; Caster, JM; Tian, X; Wang, AZ

Published Date

  • May 2015

Published In

Volume / Issue

  • 51 /

Start / End Page

  • 208 - 215

PubMed ID

  • 25771011

Pubmed Central ID

  • PMC4361776

Electronic International Standard Serial Number (EISSN)

  • 1878-5905

Digital Object Identifier (DOI)

  • 10.1016/j.biomaterials.2015.02.015

Language

  • eng

Conference Location

  • Netherlands