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

doi:10.1016/j.biomaterials.2015.02.015

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

Journal article

Open access

Peer reviewed

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 and Andrew Z Wang

Biomaterials, Vol.51, pp.208-215

05/2015

DOI: 10.1016/j.biomaterials.2015.02.015

PMCID: PMC4361776

PMID: 25771011

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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 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.

Chemotherapy

Drug delivery

Controlled drug release

Nanoparticle

Details

Title: Subtitle: Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors
Creators: Edina C Wang - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Yuanzeng Min - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Robert C Palm - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
James J Fiordalisi - Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Kyle T Wagner - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Nabeel Hyder - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Adrienne D Cox - Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Joseph M Caster - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Xi Tian - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Andrew Z Wang - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Resource Type: Journal article
Publication Details: Biomaterials, Vol.51, pp.208-215
DOI: 10.1016/j.biomaterials.2015.02.015
PMID: 25771011
PMCID: PMC4361776
NLM abbreviation: Biomaterials
ISSN: 0142-9612
eISSN: 1878-5905
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100006808, name: University of North Carolina; name: National Institutes of Health/National Cancer Institute, award: R01CA178748-01; name: National Institutes of Health Center for Nanotechnology Excellence, award: 1-U54-CA151652-01
Language: English
Date published: 05/2015
Academic Unit: Radiation Oncology
Record Identifier: 9984047894902771

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