Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor

Jie Zhang; Yaling Shi; Yueqin Zheng; Chengcheng Pan; Xiaoying Yang; Taoyan Dou; Binghe Wang; Wen Lu

doi:10.18632/oncotarget.20021

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Research Papers:

Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor

Jie Zhang, Yaling Shi, Yueqin Zheng, Chengcheng Pan, Xiaoying Yang, Taoyan Dou, Binghe Wang and Wen Lu _

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Oncotarget. 2017; 8:68242-68251. https://doi.org/10.18632/oncotarget.20021

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Abstract

Jie Zhang1, Yaling Shi1, Yueqin Zheng2, Chengcheng Pan1, Xiaoying Yang1, Taoyan Dou1, Binghe Wang2 and Wen Lu1

1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi’an, 710061, P.R. China

2Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, USA

Correspondence to:

Wen Lu, email: [email protected]

Binghe Wang, email: [email protected]

Keywords: drug delivery, histone deacetylase inhibitor, intracellular targeting, functionalized PLGA, cellular uptake

Received: June 26, 2017 Accepted: July 26, 2017 Published: August 07, 2017

ABSTRACT

Functionalized nanoparticles (NPs) are usually used to enhance cellular penetration for targeted drug delivery that can improve efficacy and reduce side effects. However, it is difficult to exploit intracellular targets for similar delivery applications. Herein we describe the targeted delivery of functionalized NPs by homing in on an intracellular target, histone deacetylases (HDACs). Specifically, a modified poly-lactide-co-glycolideacid (FPLGA) was yielded by conjugation with an HDAC inhibitor. Subsequently, FPLGA was used to prepare functionalized FPLGA NPs. Compared to unmodified NPs, FPLGA NPs were more efficiently uptaken or retained by MCF-7 cells and showed longer retention time intracellular. In vivo fluorescence imaging also revealed that they had a higher accumulation and a slower elimination than unmodified NPs. FPLGA NPs loaded with paclitaxel exhibited superior anticancer efficacy compared with unmodified NPs. These results offer a promising approach for intracellular drug delivery through elevating the concentration of NPs.

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PII: 20021

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Research Papers:

Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor

Abstract