Design of polyethylene glycol-polyethylenimine nanocomplexes as non-viral carriers: mir-150 delivery to chronic myeloid leukemia cells

被引:27
作者
Avci, Cigir Biray [1 ]
Ozcan, Ipek [2 ]
Balci, Tugce [1 ]
Ozer, Ozgen [2 ]
Gunduz, Cumhur [1 ]
机构
[1] Ege Univ, Dept Med Biol, Fac Med, Izmir, Turkey
[2] Ege Univ, Dept Pharmaceut Technol, Fac Pharm, Izmir, Turkey
关键词
leukemia; microRNA; nanoparticles; polyethylenimine; poly(ethylene glycol); GENE DELIVERY; IN-VITRO; POLYETHYLENIMINE-GRAFT-POLY(ETHYLENE GLYCOL); SIRNA; COPOLYMERS; NANOPARTICLES; PEG; THERAPY; DISEASE; MIRNA;
D O I
10.1002/cbin.10157
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many biological processes, and they have been pioneered as therapeutic targets for curing disease. miRNAs are single-stranded, small (19-22nt) regulatory non-coding RNAs whose deregulation of expression triggers human cancers, including leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs can function as tumour suppressors (suppressing malignant potential) or oncogenes (activating malignant potential) like actors of complex diseases. To address the issue of overcoming instability and low transfection efficiency in vitro, the polyethylene glycol-polyethyleneimine (PEG-PEI) nanoparticle was used as non-viral vector carrier for miR-150 transfection, which is downregulated in chronic myeloid leukemia. PEG-PEI [PEG((550)3)-g-PEI(1800)]/miRNA nanocomplexes were synthesised and characterised by particle size distribution (PSD), polydispersity index (PDI) and zeta potential, surface charge, their cytotoxicity, and transfection efficiency. Interaction with human leukemia cells (K-562 and KU812) and control cells NCI-BL2347 with them has been investigated. The transfection efficiency of PEG-PEI/miRNA at N/P 26 rose 6.7-fold above the control by qRT-PCR. The size of homogenous nanocomplexes (PBI<0.5) was 160.8 +/- 11nm. The data indicate that PEG-PEI may be an encouraging non-viral carrier for altering miRNA expression in the treatment of chronic myeloid leukemia, with many advantages such as relatively high miRNA transfection efficiency and low cytotoxicity.
引用
收藏
页码:1205 / 1214
页数:10
相关论文
共 37 条
[1]   Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth [J].
Agirre, Xabier ;
Jimenez-Velasco, Antonio ;
San Jose-Eneriz, Edurne ;
Garate, Leire ;
Bandres, Eva ;
Cordeu, Lucia ;
Aparicio, Oscar ;
Saez, Borja ;
Navarro, German ;
Vilas-Zornoza, Amaia ;
Perez-Roger, Ignacio ;
Garcia-Foncillas, Jesus ;
Torres, Antonio ;
Heiniger, Anabel ;
Jose Calasanz, Maria ;
Fortes, Puri ;
Roman-Gomez, Jose ;
Prosper, Felipe .
MOLECULAR CANCER RESEARCH, 2008, 6 (12) :1830-1840
[2]  
[Anonymous], MOL CANC
[3]   Polycation-based nanoparticle delivery of RNAi therapeutics: Adverse effects and solutions [J].
Ballarin-Gonzalez, Borja ;
Howard, Kenneth Alan .
ADVANCED DRUG DELIVERY REVIEWS, 2012, 64 (15) :1717-1729
[4]   Biodegradable Poly(ethylene carbonate) Nanoparticles as a Promising Drug Delivery System with "Stealth" Potential [J].
Bege, Nadja ;
Renette, Thomas ;
Jansch, Mirko ;
Reul, Regina ;
Merkel, Olivia ;
Petersen, Holger ;
Curdy, Catherine ;
Mueller, Rainer H. ;
Kissel, Thomas .
MACROMOLECULAR BIOSCIENCE, 2011, 11 (07) :897-904
[5]   Comparison of PEI-PEG and PLL-PEG copolymer coatings on the prevention of protein fouling [J].
Bergstrand, Anna ;
Rahmani-Monfared, Ghazal ;
Ostlund, Asa ;
Nyden, Magnus ;
Holmberg, Krister .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2009, 88A (03) :608-615
[6]   Disassembly of polyethylenimine-DNA particles in vitro: Implications for polyethylenimine-mediated DNA delivery [J].
Bertschinger, Martin ;
Backliwal, Gaurav ;
Schertenleib, Arnaud ;
Jordan, Martin ;
Hacker, David L. ;
Wurm, Florian M. .
JOURNAL OF CONTROLLED RELEASE, 2006, 116 (01) :96-104
[7]   Comparative in vivo study of poly(ethylene imine)/siRNA complexes for pulmonary delivery in mice [J].
Beyerle, Andrea ;
Braun, Andrea ;
Merkel, Olivia ;
Koch, Felix ;
Kissel, Thomas ;
Stoeger, Tobias .
JOURNAL OF CONTROLLED RELEASE, 2011, 151 (01) :51-56
[8]   A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects [J].
Bramsen, Jesper B. ;
Pakula, Malgorzata M. ;
Hansen, Thomas B. ;
Bus, Claus ;
Langkjaer, Niels ;
Odadzic, Dalibor ;
Smicius, Romualdas ;
Wengel, Suzy L. ;
Chattopadhyaya, Jyoti ;
Engels, Joachim W. ;
Herdewijn, Piet ;
Wengel, Jesper ;
Kjems, Jorgen .
NUCLEIC ACIDS RESEARCH, 2010, 38 (17) :5761-5773
[9]   Mechanistic investigation of poly(ethylene imine)-based siRNA delivery: Disulfide bonds boost intracellular release of the cargo [J].
Breunig, Miriam ;
Hozsa, Constantin ;
Lungwitz, Uta ;
Watanabe, Kazuo ;
Umeda, Isao ;
Kato, Hiroyuki ;
Goepferich, Achim .
JOURNAL OF CONTROLLED RELEASE, 2008, 130 (01) :57-63
[10]   Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells [J].
Chen, Xiao-Ai ;
Zhang, Li-Jun ;
He, Zhi-Jie ;
Wang, Wei-Wei ;
Xu, Bo ;
Zhong, Qian ;
Shuai, Xin-Tao ;
Yang, Li-Qun ;
Deng, Yu-Bin .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2011, 6