Format

Send to

Choose Destination
Nanomedicine. 2017 May;13(4):1309-1321. doi: 10.1016/j.nano.2017.01.015. Epub 2017 Feb 6.

Folate-targeted nanoparticle delivery of androgen receptor shRNA enhances the sensitivity of hormone-independent prostate cancer to radiotherapy.

Author information

1
Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
2
Cancer Institute of Xuzhou Medical University, Xuzhou, Jiangsu, China.
3
Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
4
Department of Radiation Oncology, Lianyungang Second People's Hospital, Lianyungang, Jiangsu, China.
5
Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, North, CA, USA. Electronic address: ronald_chen@med.unc.edu.
6
Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Cancer Institute of Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation for Cancer Biotheray, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: jsxzzlz@126.com.

Abstract

Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro. The radiosensitizing effect of NP AR-shRNA could be validated in vivo, as NP AR-shRNA significantly suppressed tumor growth and prolonged the survival of HIPC tumor-bearing mice. Analysis at the molecular level revealed that NP AR-shRNA inhibits DNA damage repair signaling pathways. Our study supports further investigation of NP AR-shRNA for the improvement of radiotherapy efficacy in HIPC.

KEYWORDS:

Androgen receptor interference; Hormone-independent prostate cancer; Nanoparticle; Radiosensitivity; Subcutaneous xenotransplanted tumor model

PMID:
28185938
DOI:
10.1016/j.nano.2017.01.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center