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

被引：60

作者：

Wang, Edina C. ^{[1
,2
]}

Min, Yuanzeng ^{[1
,2
]}

Palm, Robert C. ^{[1
,2
]}

Fiordalisi, James J. ^{[2
]}

Wagner, Kyle T. ^{[1
,2
]}

Hyder, Nabeel ^{[1
,2
]}

Cox, Adrienne D. ^{[2
]}

Caster, Joseph M. ^{[1
]}

Tian, Xi ^{[1
,2
]}

Wang, Andrew Z. ^{[1
,2
]}

机构：

[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Carolina Ctr Canc Nanotechnol Excellence, Lab Nano & Translat Med,Carolina Inst Nanomed, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Radiat Oncol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

来源：

BIOMATERIALS | 2015年 / 51卷

基金：

美国国家卫生研究院;

关键词：

Nanoparticle; Drug delivery; Chemotherapy; Controlled drug release; GAMMA-H2AX FOCI; PHASE-I; CANCER; RADIATION; CELLS; RADIOSENSITIZATION; PROLONGATION; VORINOSTAT; MODULATION; BREAKS;

D O I：

10.1016/j.biomaterials.2015.02.015

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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 gamma-H2AX foci. Our work illustrates an effective method for improving cancer radiotherapy treatment. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：208 / 215

页数：8

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