Maedeh Ghaffari1, Seyed Mehdi Kalantar2, Mahdie Hemati3,4, Ali Dehghani Firoozabadi5, Amir Asri6, Ali Shams7, Sina Jafari Ghalekohneh8, Fateme Haghiralsadat9,10. 1. Department of Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 2. Genetic and Reproductive Unit, Recurrent Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 3. Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 4. Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 5. Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 6. Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. 7. Immunology Department, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 8. Department of Mechanical Engineering, University of Tehran, Tehran, Iran. 9. Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. fhaghirosadat@gmail.com. 10. Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. fhaghirosadat@gmail.com.
Abstract
OBJECTIVE: Tumor suppressor miRNAs, miR-15a and miR-16-1, with high-specificity and oncogenic targeting of Bcl-2, can target tumor tissues. Disadvantages of the clinical application of free miRNAs include poor cellular uptake and instability in plasma, which can be partially improved by using nanocarriers to deliver anti-cancer agents to the tumor cell. METHOD: In this study, cationic niosomes were designed and optimized with the specific formulation. Then, the physical characteristics, the cytotoxicity, the impact of transfected miRNAs on the expression of the Bcl-2 gene, and the apoptosis rate of the different formulation into prostate cancer cell were determined. RESULTS: The optimum formulation containing tween-60: cholesterol: DOTAP: DSPE-PEG2000 at 70:30:25:5 demonstrated that the vesicle size and zeta potentials were 69.7 nm and + 14.83 mV, respectively. Additionally, noisome-loaded miRNAs had higher toxicity against cancer cells comparing with free forms. The transfection of PC3 cells with the combination therapy of nanocarriers loaded of two miRNAs led to a significant decrease in the expression of the Bcl-2 gene and increased the degree of cell death in PC3 cells compared with other treatment groups, and the synergistic effects of co-delivery of miR-15a and miR-16-1 on prostate cancer cells were shown. CONCLUSION: According to the results, it seems the designed niosomes containing miR-15a and miR-16-1 can target the Bcl-2 gene and provide a cheap, applicable, cost-effective, and safe drug delivery system against prostate cancer.
OBJECTIVE:Tumor suppressor miRNAs, miR-15a and miR-16-1, with high-specificity and oncogenic targeting of Bcl-2, can target tumor tissues. Disadvantages of the clinical application of free miRNAs include poor cellular uptake and instability in plasma, which can be partially improved by using nanocarriers to deliver anti-cancer agents to the tumor cell. METHOD: In this study, cationic niosomes were designed and optimized with the specific formulation. Then, the physical characteristics, the cytotoxicity, the impact of transfected miRNAs on the expression of the Bcl-2 gene, and the apoptosis rate of the different formulation into prostate cancer cell were determined. RESULTS: The optimum formulation containing tween-60: cholesterol: DOTAP: DSPE-PEG2000 at 70:30:25:5 demonstrated that the vesicle size and zeta potentials were 69.7 nm and + 14.83 mV, respectively. Additionally, noisome-loaded miRNAs had higher toxicity against cancer cells comparing with free forms. The transfection of PC3 cells with the combination therapy of nanocarriers loaded of two miRNAs led to a significant decrease in the expression of the Bcl-2 gene and increased the degree of cell death in PC3 cells compared with other treatment groups, and the synergistic effects of co-delivery of miR-15a and miR-16-1 on prostate cancer cells were shown. CONCLUSION: According to the results, it seems the designed niosomes containing miR-15a and miR-16-1 can target the Bcl-2 gene and provide a cheap, applicable, cost-effective, and safe drug delivery system against prostate cancer.
Authors: Amelia Cimmino; George Adrian Calin; Muller Fabbri; Marilena V Iorio; Manuela Ferracin; Masayoshi Shimizu; Sylwia E Wojcik; Rami I Aqeilan; Simona Zupo; Mariella Dono; Laura Rassenti; Hansjuerg Alder; Stefano Volinia; Chang-Gong Liu; Thomas J Kipps; Massimo Negrini; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2005-09-15 Impact factor: 11.205