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

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 journal › Article › peer-review

59 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 language	English (US)
Pages (from-to)	208-215
Number of pages	8
Journal	Biomaterials
Volume	51
DOIs	https://doi.org/10.1016/j.biomaterials.2015.02.015
State	Published - May 1 2015
Externally published	Yes

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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10.1016/j.biomaterials.2015.02.015

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title = "Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors",

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.",

keywords = "Chemotherapy, Controlled drug release, Drug delivery, Nanoparticle",

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

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

month = may,

day = "1",

doi = "10.1016/j.biomaterials.2015.02.015",

language = "English (US)",

volume = "51",

pages = "208--215",

journal = "Biomaterials",

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publisher = "Elsevier BV",

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T1 - Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors

AU - Wang, Edina C.

AU - Min, Yuanzeng

AU - Palm, Robert C.

AU - Fiordalisi, James J.

AU - Wagner, Kyle T.

AU - Hyder, Nabeel

AU - Cox, Adrienne D.

AU - Caster, Joseph M.

AU - Tian, Xi

AU - Wang, Andrew Z.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Chemotherapy

KW - Controlled drug release

KW - Drug delivery

KW - Nanoparticle

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DO - 10.1016/j.biomaterials.2015.02.015

M3 - Article

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AN - SCOPUS:84924869222

SN - 0142-9612

VL - 51

SP - 208

EP - 215

JO - Biomaterials

JF - Biomaterials

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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