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

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. Copyright © 2017 Elsevier Inc. All rights reserved.

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Xinjun Zhang, Nianli Liu, ZhiYing Shao, Hui Qiu, Hong Yao, JiaYin Ji, Jianshe Wang, Wenchao Lu, Ronald C Chen, Longzhen Zhang. Folate-targeted nanoparticle delivery of androgen receptor shRNA enhances the sensitivity of hormone-independent prostate cancer to radiotherapy. Nanomedicine : nanotechnology, biology, and medicine. 2017 May;13(4):1309-1321

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PMID: 28185938

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