|
|
|
| Targeted Delivery of siRNA Mediated by Aptamer Modified Liposome |
| TANG De-ping1, MAO Ai-hong2, WANG Fang2, ZHANG Hong2, WANG Li2, LIAO Shi-qi2 |
1. The School of Chemical & Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China;
2. Institute of Gansu Medical Science Research, Lanzhou 730050, China |
|
|
|
Abstract To investigate the efficiency of siRNA using aptamer-conjugated liposome(Apt-LP),A10-3.2 was used as a PSMA-targeting ligand in the design of a liposome-based siRNA delivery system to prostate cancer cells. The sequence of the aptamer used in this study is modified with 3'- Cholesterol and with 2'- Fluor pyrimidines. The cholesterol tag immobilizes the aptamer on the liposome surface by inserting into the hydrophobic lipid membrane. Liposome was conjugated to aptamer and used as a vehicle for siRNA target delivery. GFP expression assays of pEGFP - N1 against LNCaP (PSMA+) and PC-3 (PSMA-) cells demonstrated that the transfection efficiency of the synthesized Apt-LP complex was higher than that of the liposome. In addition, gene knock down assay of Apt-LP-siRNA complex in LNCaP (PSMA+) and PC-3 (PSMA-) cells showed that Bcl2 gene silencing effect significantly higher than that of LP-siRNA complex and more effectively induced apoptosis of LNCaP cells. These results suggest that the Apt - LP is a kind of effective siRNA targeting delivery system, has potential clinical application.
|
|
Received: 27 June 2014
Published: 25 January 2015
|
|
|
|
|
|
[1] Boutros M, Ahringer J. The art and design of genetic screens: RNA interference. Nature Reviews Genetics, 2008. 9(7): 554-566.
[2] Lares M R, Rossi J J, Ouellet D L, RNAi and small interfering RNAs in human disease therapeutic applications. Trends in Biotechnology, 2010. 28(11):570-579.
[3] Bunka D H, Platonova O, Stockley P G. Development of aptamer therapeutics. Current Opinion in Pharmacology, 2010. 10(5): 557-562.
[4] Yan A C, Levy M. Aptamers and aptamer targeted delivery. RNA Biol, 2009. 6(3): 316-320.
[5] Lupold S E, Hicke B J, Lin Y,et al. Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Research, 2002. 62(14): 4029-4033.
[6] Farokhzad O C, Jon S, Khademhosseini A,et al. Nanoparticle-aptamer bioconjugates a new approach for targeting prostate cancer cells. Cancer Research, 2004. 64(21): 7668-7672.
[7] Cheng J, Teply B A, Sherifi I,et al. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials, 2007. 28(5): 869-876.
[8] Dhar S, Gu F X, Langer R,et al. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt (IV) prodrug-PLGA-PEG nanoparticles. Proceedings of the National Academy of Sciences, 2008. 105(45): 17356-17361.
[9] Dhar S, Kolishetti N, Lippard S J,et al. Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proceedings of the National Academy of Sciences, 2011. 108(5): 1850-1855.
[10] McNamara J O, Andrechek E R, Wang Y, et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nature Biotechnology, 2006. 24(8): 1005-1015.
[11] Kim E, Jung Y, Choi Het al. Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex. Biomaterials, 2010. 31(16): 4592-4599.
[12] Chu T C, Twu K Y, Ellington A D,et al. Aptamer mediated siRNA delivery. Nucleic Acids Research, 2006. 34(10): e73.
[13] Wu X, Ding B, Gao J, et al. Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy. Int J Nanomedicine, 2011. 6: 1747-1756.
[14] Dassie J P, Liu X Y, Thomas G S, et al. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nature Biotechnology, 2009. 27(9): 839-849.
[15] Ghosh A, Heston W D. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. Journal of Cellular Biochemistry, 2004. 91(3): 528-539.
[16] Chu T C, Marks J W 3rd, Lavery L A, et al. Aptamer: toxin conjugates that specifically target prostate tumor cells. Cancer Research, 2006. 66(12): 5989-5992.
[17] Farokhzad O C, Cheng J, Teply B A, et al. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proceedings of the National Academy of Sciences, 2006. 103(16): 6315-6320.
[18] Pastor F, Kolonias D, Giangrande P H, et al. Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay. Nature, 2010. 465(7295): 227-230.
[19] Wullner U, Neef I, Eller A, et al. Cell-specific induction of apoptosis by rationally designed bivalent aptamer-siRNA transcripts silencing eukaryotic elongation factor 2. Current Cancer Drug Targets, 2008. 8(7): 554-565.
[20] Cao Z, Tong R, Mishra A, et al. Reversible Cell-Specific Drug Delivery with Aptamer-Functionalized Liposomes. Angewandte Chemie International Edition, 2009. 48(35): 6494-6498.
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
