title: Folate-targeted nanoparticle delivery of androgen receptor shRNA enhances the sensitivity of hormone-independent prostate cancer to radiotherapy.
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.
authors.affiliation: Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cancer Institute of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Nianli
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: ZhiYing
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Cancer Institute of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Cancer Institute of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: JiaYin
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Lianyungang Second People's Hospital, Lianyungang, Jiangsu, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Zhang
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D059002:Androgen Receptor Antagonists; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D005492:Folic Acid
keywords: Androgen receptor interference; Hormone-independent prostate cancer; Nanoparticle; Radiosensitivity; Subcutaneous xenotransplanted tumor model