title: Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo.
abstract: Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to "castration-resistant prostate cancer" (CRPC). Thus, more effective therapeutic strategies are required. Quercetin (QCT) is a natural flavonoid compound that has attracted increasing interest due to its anticancer activity. However, the clinical application of quercetin is largely hampered by its poor water solubility and low bioavailability. The objective of this study was to evaluate the therapeutic potential of novel QCT-loaded nanomicelles (M-QCTs) assembled from DSPE-PEG2000 for prostate cancer treatment. Our results indicated that QCT was efficiently encapsulated into micelles up to 1 mg mL(-1), which corresponds to a 450-fold increase of its water solubility. In vitro studies showed that the half-maximal inhibitory concentration (IC50) value (20.2 μM) of M-QCTs was much lower than free QCT (>200 μM). Thus, M-QCTs were considerably more effective than free QCT in proliferation inhibition and apoptosis induction of human androgen-independent PC-3 cells. Furthermore, M-QCTs showed superior antitumor efficacy and the tumor proliferation rate reduced by 52.03% compared to the control group in the PC-3 xenograft mouse model, possibly due to increased accumulation of M-QCTs at the tumor site by the enhanced permeability and retention (EPR) effect. Collectively, our studies demonstrated that M-QCTs significantly increase drug accumulation at the tumor site and exhibit superior anticancer activity in prostate cancer. Thus, our nanomicelle-based drug delivery system constitutes a promising and effective therapeutic strategy for clinical treatment.
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050016, China. xlduan0311@163.com and CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn and Department of Histology and Embryology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn.
authors.forename: Tuo
authors.initials: T
authors.lastname: Wei
authors.affiliation: CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn.
authors.forename: Shuaidong
authors.initials: S
authors.lastname: Huo
authors.affiliation: CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn.
authors.forename: Chunqiu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050016, China. xlduan0311@163.com.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Duan
authors.affiliation: CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China. liangxj@nanoctr.cn.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism*; D011794:Quercetin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011794:Quercetin