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

Edina C. Wang, Yuanzeng Min, Robert C. Palm, James J. Fiordalisi, Kyle T. Wagner, Nabeel Hyder, Adrienne D. Cox, Joseph M. Caster, Xi Tian, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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 invitro and are more effective as radiosensitizers than small molecule HDACIs invivo 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.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalBiomaterials
Volume51
DOIs
StatePublished - May 1 2015
Externally publishedYes

Keywords

  • Chemotherapy
  • Controlled drug release
  • Drug delivery
  • Nanoparticle

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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