Yiran Zhang1,2,3, Yanming Wang4, Li Meng4, Qingqing Huang4, Yueqi Zhu2, Wenguo Cui5, Yingsheng Cheng6, Ranlu Liu7. 1. Tianjin Institute of Urology & Department of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin, 300211, People's Republic of China. 2. Department of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, People's Republic of China. 3. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China. 4. Tianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. 5. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China. wgcui80@hotmail.com. 6. Department of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, People's Republic of China. chengyingshengradio@hotmail.com. 7. Tianjin Institute of Urology & Department of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin, 300211, People's Republic of China. liuranlu1976@126.com.
Abstract
BACKGROUND: Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. RESULTS: The particle size of the micelles was 42 nm, the zeta potential increased from - 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. CONCLUSIONS: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.
<span class="abstract_title">BACKGROUND: C<ne">span class="Chemical">hemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCLmicelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. RESULTS: The particle size of themicelles was 42 nm, thezeta potential increased from - 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of theDCL ligand resulted in high toxicity toward PSMA-positive cells and that theTAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and thetumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. CONCLUSIONS: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.
Authors: Philip Cornford; Joaquim Bellmunt; Michel Bolla; Erik Briers; Maria De Santis; Tobias Gross; Ann M Henry; Steven Joniau; Thomas B Lam; Malcolm D Mason; Henk G van der Poel; Theo H van der Kwast; Olivier Rouvière; Thomas Wiegel; Nicolas Mottet Journal: Eur Urol Date: 2016-08-31 Impact factor: 20.096
Authors: Esther W Bouman-Wammes; H Pieter van den Berg; Linda de Munck; Aart Beeker; Carolien H Smorenburg; Walter L Vervenne; Juleon L L M Coenen; Henk M W Verheul; Winald R Gerritsen; Alfons J M Van den Eertwegh Journal: Eur J Cancer Date: 2017-12-18 Impact factor: 9.162
Authors: Christopher J Sweeney; Yu-Hui Chen; Michael Carducci; Glenn Liu; David F Jarrard; Mario Eisenberger; Yu-Ning Wong; Noah Hahn; Manish Kohli; Matthew M Cooney; Robert Dreicer; Nicholas J Vogelzang; Joel Picus; Daniel Shevrin; Maha Hussain; Jorge A Garcia; Robert S DiPaola Journal: N Engl J Med Date: 2015-08-05 Impact factor: 91.245