Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo

被引:65
|
作者
Zhao, Jing [1 ,2 ,3 ,4 ]
Liu, Juan [2 ,3 ]
Wei, Tuo [2 ,3 ]
Ma, Xiaowei [2 ,3 ]
Cheng, Qiang [5 ]
Huo, Shuaidong [2 ,3 ]
Zhang, Chunqiu [2 ,3 ]
Zhang, Yanan [4 ]
Duan, Xianglin [1 ]
Liang, Xing-Jie [2 ,3 ]
机构
[1] Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Peoples R China
[2] Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, 11 First North Rd, Beijing 100190, Peoples R China
[3] Natl Ctr Nanosci & Technol, CAS Key Lab Biol Effects Nanomat & Nanosafety, 11 First North Rd, Beijing 100190, Peoples R China
[4] Hebei Med Univ, Dept Histol & Embryol, Shijiazhuang 050017, Peoples R China
[5] Peking Univ, Inst Mol Med, Lab Nucle Acid Technol, Beijing 100871, Peoples R China
关键词
DRUG-DELIVERY; ANTIOXIDANT ACTIVITY; DOCETAXEL; PHARMACOKINETICS; NANOPARTICLES; PLATFORM;
D O I
10.1039/c5nr08966b
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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-PEG(2000) 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 mu M) of M-QCTs was much lower than free QCT (>200 mu M). 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.
引用
收藏
页码:5126 / 5138
页数:13
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