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

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.Chinese Natural Science Foundation key project [31430031]; National Distinguished Young Scholars grant [31225009]; State High-Tech Development Plan [2012AA020804, SS2014AA020708]; Natural Science Foundation of Hebei province, China [C2014206350]; external cooperation program of BIC, Chinese Academy of Science [121D11KYSB20130006]; "Strategic Priority Research Program" of the Chinese Academy of Sciences [XDA09030301]SCI(E)EIPubMedARTICLExlduan0311@163.com; liangxj@nanoctr.cn95126-5138