Volume 23, Issue 2 (2020)
mjms 2020, 23(2): 109-119 |
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Kamalzare S, Noormohammadi Z, Rahimi P, Atyabi F, Irani S, Mirzazadeh Tekie F et al . Optimization of Superparamagnetic Iron Oxide Nanoparticles-Trimethyl Chitosan (SPION-TMC) as a siRNA Carrier to Inhibit HIV-1 nef. mjms 2020; 23 (2) :109-119
URL: http://mjms.modares.ac.ir/article-30-41130-en.html
URL: http://mjms.modares.ac.ir/article-30-41130-en.html
S. Kamalzare1 
, Z. Noormohammadi1 , P. Rahimi 2, F. Atyabi3 , Sh. Irani1 , F.S. Mirzazadeh Tekie4 , F. Mottaghitalab4
, Z. Noormohammadi1 , P. Rahimi 2, F. Atyabi3 , Sh. Irani1 , F.S. Mirzazadeh Tekie4 , F. Mottaghitalab4
1- Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University (IAU), Tehran, Iran
2- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran , prahimi@pasteur.ac.ir
3- “Nanotechnology Research Centre” and “Department of Pharmaceutics, Faculty of Pharmacy”, Tehran Uni‐ versity of Medical Sciences, Tehran, Iran
4- Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, Iran
2- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran , prahimi@pasteur.ac.ir
3- “Nanotechnology Research Centre” and “Department of Pharmaceutics, Faculty of Pharmacy”, Tehran Uni‐ versity of Medical Sciences, Tehran, Iran
4- Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, Iran
Abstract: (1734 Views)
Aims: Despite the efficacy of current therapies against HIV-1 infection, these methods are not a permanent treatment because they cannot prevent the return of viremia from latent cell reservoirs. On the other hand, the virus may become resistant to these drugs. Therefore, providing safer and more effective therapeutic strategies, such as inhibition of genes by siRNA, is essential. The successful therapeutic application of siRNAs requires an efficient delivery system to target cells.
Materials & Methods: In this study, a specific siRNA was designed against the HIV-1 nef gene. Then a stable HEK293 cell line expressing HIV-1 nef was developed and after fabrication and evaluation of superparamagnetic iron oxide nanoparticles (SPION) coated with trimethyl chitosan, the efficiency of nanoparticles for delivering siRNA into the cells and inhibition of nef gene was investigated.
Findings: Iron oxide nanoparticles (spherical-shaped with an average size of 85nm and the average zeta potential of +29mV) were significantly effective in transporting siRNA into HEK293 cells compared to control groups and at the same time had low toxicity to the cells. In addition, SPION-TMC containing anti-nef siRNA inhibited about 85% of the expression of this gene in stable cells (compared to control cells).
Conclusion: The optimized SPION-TMC nanocarriers can be used as a promising approach in HIV-1 infection therapy. However, pre-clinical in vivo evaluation of the drug/siRNA delivery system efficiency remains to be conducted.
Materials & Methods: In this study, a specific siRNA was designed against the HIV-1 nef gene. Then a stable HEK293 cell line expressing HIV-1 nef was developed and after fabrication and evaluation of superparamagnetic iron oxide nanoparticles (SPION) coated with trimethyl chitosan, the efficiency of nanoparticles for delivering siRNA into the cells and inhibition of nef gene was investigated.
Findings: Iron oxide nanoparticles (spherical-shaped with an average size of 85nm and the average zeta potential of +29mV) were significantly effective in transporting siRNA into HEK293 cells compared to control groups and at the same time had low toxicity to the cells. In addition, SPION-TMC containing anti-nef siRNA inhibited about 85% of the expression of this gene in stable cells (compared to control cells).
Conclusion: The optimized SPION-TMC nanocarriers can be used as a promising approach in HIV-1 infection therapy. However, pre-clinical in vivo evaluation of the drug/siRNA delivery system efficiency remains to be conducted.
Article Type: Original Research |
Subject:
Nanotechnology
Received: 2020/03/2 | Accepted: 2020/07/22
Received: 2020/03/2 | Accepted: 2020/07/22
References
1. Ghane T, Zamani N, Hassanian-Moghaddam H, Beyrami A, Noroozi A. Lead poisoning outbreak among opium users in the Islamic Republic of Iran, 2016-2017. Bull World Health Organ. 2018;96(3):165-72. [Link] [DOI:10.2471/BLT.17.196287]
2. Reeves JD, Doms RW. Human immunodeficiency virus type 2. J Gener Virol. 2002;83(6):1253-65. [Link] [DOI:10.1099/0022-1317-83-6-1253]
3. Imlach S, McBreen S, Shirafuji T, Leen C, Bell J, Simmonds P. Activated peripheral CD8 lymphocytes express CD4 in vivo and are targets for infection by human immunodeficiency virus type 1. J Virol. 2001;75(23):11555-64. [Link] [DOI:10.1128/JVI.75.23.11555-11564.2001]
4. Johnson VA, Calvez V, Günthard HF, Paredes R, Pillay D, Shafer RW, et al. Update of the drug resistance mutations in HIV-1: March 2013. Top Antivir Med. 2013;21(1):6-7. [Link]
5. Narute P. Insights into RNA interference as antiviral defense. J AIDS Clin Res. 2016;7(8):1000598. [Link] [DOI:10.4172/2155-6113.1000598]
6. Kamalzare S, Noormohammadi Z, Rahimi P, Atyabi F, Irani S, Tekie FS, et al. Carboxymethyl dextran‐trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV‐1 Nef. J Cell Physiol. 2019;234(11):20554-65. [Link] [DOI:10.1002/jcp.28655]
7. Bobbin ML, Burnett JC, Rossi JJ. RNA interference approaches for treatment of HIV-1 infection. Genome Med. 2015;7(1):50. [Link] [DOI:10.1186/s13073-015-0174-y]
8. Danner J, Pai B, Wankerl L, Meister G. Peptide-based inhibition of miRNA-guided gene silencing. In: Schmidt MF, editor. Drug target miRNA. New York: Humana Press; 2017. pp. 199-210. [Link] [DOI:10.1007/978-1-4939-6563-2_14]
9. Miyagishi M, Hayashi M, Taira K. Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells. Antisense Nucleic Acid Drug Dev. 2003;13(1):1-7. [Link] [DOI:10.1089/108729003764097296]
10. Abdelrahman M, Eyrolles LD, Alkarib SY, Hervé-Aubert K, Djemaa SB, Marchais H, et al. siRNA delivery system based on magnetic nanovectors: Characterization and stability evaluation. Eur J Pharm Sci. 2017;106:287-93. [Link] [DOI:10.1016/j.ejps.2017.05.062]
11. Williams JP, Southern P, Lissina A, Christian HC, Sewell AK, Phillips R, et al. Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity. Int J Nanomed. 2013;8:2543-54. [Link] [DOI:10.2147/IJN.S44013]
12. Hamman JH, Kotze AF. Effect of the type of base and number of reaction steps on the degree of quaternization and molecular weight of N-trimethyl chitosan chloride. Drug Dev Ind Pharm. 2001;27(5):373-80. [Link] [DOI:10.1081/DDC-100104312]
13. Thermo Fisher Scientific. BLOCK‐iT™ RNAi Designer. Online Version [software]. 2009 [cited 2018 May 10]. Available from: https://rnaidesigner.thermofisher.com/rnaiexpress [Link]
14. Swamy MN, Wu H, Shankar P. Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS. Adv Drug Deliv Rev. 2016;103:174-86. [Link] [DOI:10.1016/j.addr.2016.03.005]
15. Mobarakeh VI, Modarressi MH, Rahimi P, Bolhassani A, Arefian E, Atyabi F, et al. Optimization of chitosan nanoparticles as an anti-HIV siRNA delivery vehicle. Int J Biol Macromol. 2019;129:305-15. [Link] [DOI:10.1016/j.ijbiomac.2019.02.036]
16. Adesina SK, Akala EO. Nanotechnology approaches for the delivery of exogenous siRNA for HIV therapy. Mol Pharm. 2015;12(12):4175-87. [Link] [DOI:10.1021/acs.molpharmaceut.5b00335]
17. Mulens-Arias V, Rojas JM, Pérez-Yagüe S, del Puerto Morales M, Barber DF. Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells. J Controll Release. 2015;216:78-92. [Link] [DOI:10.1016/j.jconrel.2015.08.009]
18. Sharifi S, Seyednejad H, Laurent S, Atyabi F, Saei AA, Mahmoudi M. Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging. Contrast Media Mol Imaging. 2015;10(5):329-55. [Link] [DOI:10.1002/cmmi.1638]
19. Luo X, Peng X, Hou J, Wu S, Shen J, Wang L. Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer. Int J Nanomed. 2017;12:5331-43. [Link] [DOI:10.2147/IJN.S137245]
20. Yang Z, Duan J, Wang J, Liu Q, Shang R, Yang X, et al. Superparamagnetic iron oxide nanoparticles modified with polyethylenimine and galactose for siRNA targeted delivery in hepatocellular carcinoma therapy. Int J Nanomed. 2018;13:1851-65. [Link] [DOI:10.2147/IJN.S155537]
21. Yan L, Luo L, Amirshaghaghi A, Miller J, Meng C, You T, et al. Dextran-benzoporphyrin derivative (BPD) coated superparamagnetic iron oxide nanoparticle (SPION) micelles for T2-weighted magnetic resonance imaging and photodynamic therapy. Bioconjugate Chem. 2019;30(11):2974-81. [Link] [DOI:10.1021/acs.bioconjchem.9b00676]
22. Mulens-Arias V, Rojas JM, Sanz-Ortega L, Portilla Y, Pérez-Yagüe S, Barber DF. Polyethylenimine-coated superparamagnetic iron oxide nanoparticles impair in vitro and in vivo angiogenesis. Nanomed Nanotechnol Biol Med. 2019;21:102063. [Link] [DOI:10.1016/j.nano.2019.102063]
23. Meisel CL, Bainbridge P, Mulkern RV, Mitsouras D, Wong JY. Assessment of superparamagnetic iron oxide nanoparticle poly (ethylene glycol) coatings on magnetic resonance relaxation for early disease detection. IEEE Open J Eng Med Biol. 2020;1:116-22. [Link] [DOI:10.1109/OJEMB.2020.2989468]
24. Galli M, Rossotti B, Arosio P, Ferretti AM, Panigati M, Ranucci E, et al. A new catechol-functionalized polyamidoamine as an effective SPION stabilizer. Colloids Surf B Biointerfaces. 2019;174:260-9. [Link] [DOI:10.1016/j.colsurfb.2018.11.007]
25. Jeon H, Kim J, Lee YM, Kim J, Choi HW, Lee J, et al. Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system. J Controll Release. 2016;231:68-76. [Link] [DOI:10.1016/j.jconrel.2016.01.006]
26. Thomas RG, Muthiah M, Moon M, Park IK, Jeong YY. SPION loaded poly (L-lysine)/hyaluronic acid micelles as MR contrast agent and gene delivery vehicle for cancer theranostics. Macromol Res. 2017;25(5):446-51. [Link] [DOI:10.1007/s13233-017-5053-5]
27. Yemisci M, Caban S, Fernandez-Megia E, Capan Y, Couvreur P, Dalkara T. Preparation and characterization of biocompatible chitosan nanoparticles for targeted brain delivery of peptides. In: Skaper SD, editor. Neurotrophic factors. New York: Humana Press; 2018. pp. 443-54. [Link] [DOI:10.1007/978-1-4939-7571-6_36]
28. Nimesh S, Gupta N, Chandra R. Cationic polymer based nanocarriers for delivery of therapeutic nucleic acids. J Biomed Nanotechnol. 2011;7(4):504-20. [Link] [DOI:10.1166/jbn.2011.1313]
29. David S, Marchais H, Hervé-Aubert K, Bedin D, Garin AS, Hoinard C, et al. Use of experimental design methodology for the development of new magnetic siRNA nanovectors (MSN). Int J Pharm. 2013;454(2):660-7. [Link] [DOI:10.1016/j.ijpharm.2013.05.051]
30. Mohammadi-Samani S, Miri R, Salmanpour M, Khalighian N, Sotoudeh S, Erfani N. Preparation and assessment of chitosan-coated superparamagnetic Fe3O4 nanoparticles for controlled delivery of methotrexate. Res Pharm Sci. 2013;8(1):25-33. [Link]
31. Mansouri M, Nazarpak MH, Solouk A, Akbari S, Hasani-Sadrabadi MM. Magnetic responsive of paclitaxel delivery system based on SPION and palmitoyl chitosan. J Magn Magn Mater. 2017;421:316-25. [Link] [DOI:10.1016/j.jmmm.2016.07.066]
32. Berg JM, Romoser A, Banerjee N, Zebda R, Sayes CM. The relationship between pH and zeta potential of∼ 30 nm metal oxide nanoparticle suspensions relevant to in vitro toxicological evaluations. Nanotoxicology. 2009;3(4):276-83. [Link] [DOI:10.3109/17435390903276941]
33. Seil JT, Webster TJ. Antimicrobial applications of nanotechnology: Methods and literature. Int J Nanomed. 2012;7:2767-81. [Link] [DOI:10.2147/IJN.S24805]
34. Perera G, Zipser M, Bonengel S, Salvenmoser W, Bernkop-Schnürch A. Development of phosphorylated nanoparticles as zeta potential inverting systems. Eur J Pharm Biopharm. 2015;97(Part A):250-6. [Link] [DOI:10.1016/j.ejpb.2015.01.017]
35. Furuike T, Komoto D, Hashimoto H, Tamura H. Preparation of chitosan hydrogel and its solubility in organic acids. Int J Biol Macromol. 2017;104(Part B):1620-5. [Link] [DOI:10.1016/j.ijbiomac.2017.02.099]
36. Ahmad S, Zamry AA, Tan H-TT, Wong KK, Lim J, Mohamud R. Targeting dendritic cells through gold nanoparticles: A review on the cellular uptake and subsequent immunological properties. Mol Immunol. 2017;91:123-33. [Link] [DOI:10.1016/j.molimm.2017.09.001]
37. Liu X, Mo Y, Liu X, Guo R, Zhang Y, Xue W, et al. Synthesis, characterisation and preliminary investigation of the haemocompatibility of polyethyleneimine-grafted carboxymethyl chitosan for gene delivery. Mater Sci Eng C. 2016;62:173-82. [Link] [DOI:10.1016/j.msec.2016.01.050]
38. Lindemann A, Pries R, Lüdtke-Buzug K, Wollenberg B. Biological properties of superparamagnetic iron oxide nanoparticles. IEEE Trans Magn. 2015;51(2):1-4. [Link] [DOI:10.1109/TMAG.2014.2358257]
39. Nguyen VT. Magnetic polyion complex micelles as therapy and diagnostic agents [Dissertation]. Waterloo: UWSpace; 2015. [Link]
40. Hamzian N, Hashemi M, Ghorbani M, Bahreyni Toosi MH, Ramezani M. Preparation, optimization and toxicity evaluation of (SPION-PLGA)±PEG nanoparticles loaded with Gemcitabine as a multifunctional nanoparticle for therapeutic and diagnostic applications. Iran J Pharm Res. 2017;16(1):8-21. [Link]
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