Improved Magnetofection Efficiency of Polyethylene-modified Fe3O4 Nanoparticles by Exerting a Uniform Magnetic Field
XIE Lina1,2,3,4, LUO Cong2, WU Jiamin5, WANG Changxuan1,2,3,4, WU Jun2
1 Ministry of Education Key Laboratory of Child Development and Disorders, Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing 400014; 2 Department of Orthopaedics, Children’s Hospital of ChongqingMedical University, Chongqing 400014; 3 China International Science and Technology Cooperation Base of ChildDevelopment and Critical Disorders, Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing 400014; 4 Key Laboratory of Pediatrics, Pediatric Research Institute, Children’s Hospital of ChongqingMedical University, Chongqing 400014; 5 State Key Laboratory of Power Transmission Equipment and SystemSecurity and New Technology, School of Electrical Engineering, Chongqing University, Chongqing 400044
Abstract: The effect of uniform magnetic field(MF) on magnetofection was studied for the first time. The uniformity of the unilateral Halbach magnet and the commercialized 96 hole magnet were measured. Polyethyleneimine (PEI) modified ferroferric oxide (Fe3O4) nanoparticles (PEI-Fe3O4) were prepared by chemical coprecipitation. The morphology, composition and the DNA binding ability of PEI-Fe3O4were charaterized by transmission electron microscope (TEM), vibrating sample magnetometer (VSM), atomic force microscopy and agarose gel electrophoresis. The green fluorescent protein (GFP) expression efficiency in human renal epithelial cells (HEK293) under different uniformity of magnetic field was detected with inverted fluorescence microscope and flow cytometry. The phagocytosis of PEI-Fe3O4nanoparticles was observed by TEM. The results showed that the difference of uniformity of the two magnetic fields was about 100 times. The superparamagnetic PEI-Fe3O4 has a good compound ability for plasmid pDNA, and its optimal combination ratio is N/P=0.5. Flow cytometry showed that the transfection efficiency was: PEI-Fe3O4-pDNA+ uniform MF group (77.75%±0.07%)>PEI-Fe3O4-pDNA+ nonuniform MF group (30.65%±0.49%)>PEI-Fe3O4-pDNA without MF group (7.90%±0.56%) (p<0.05). PEI-Fe3O4 magnetic nanoparticles can be effectively consumed by cells and have little effect on cell morphology. It can be concluded that when the magnetic field intensity is certain, higher uniformity of magnetic field contributes to the higher the magnetic transfection efficiency. The combination of the unilateral Halbach magnet and the magnetosfection can be used as a new method to improve the transfection rate, which may potentially be employed in gene therapy.
1 Orkin S H, Reilly P. Medicine. Paying for future success in gene therapy[J].Science,2016,352(6289):1059. 2 Buchschacher G L, Wong-Staal F. Development of lentiviral vectors for gene therapy for human diseases[J].Blood,2000,95(8):2499. 3 Raisin S, Morille M, Bony C, et al. Tripartite polyionic complex (PIC) micelles as non-viral vectors for mesenchymal stem cell siRNA transfection[J].Biomaterials Science,2017,5(9):1910. 4 Hardee C L, Arévalo-Soliz L M, Hornstein B D, et al. Advances in non-viral DNA vectors for gene therapy[J].Genes(Basel),2017,8(2):65. 5 Khabou H, Dalkara D. Developments in gene delivery vectors for ocular gene therapy[J].Medecine Sciences M/s(Paris),2015,31(5):529. 6 Goodwin T, Huang L. Nonviral vectors: We have come a long way[J].Advances in Genetics,2014,88:1. 7 Vainauska D, Kozireva S, Karpovs A, et al. A novel approach for nucleic acid delivery into cancer cells[J].Medicina (Kaunas),2012,48(6):324. 8 Smolders S, Kessels S, Smolders S M, et al. Magnetofection is superior to other chemical transfection methods in a microglial cell line[J].Journal of Neuroscience Methods,2017,293:169. 9 Laurentt N, Sapet C, Le G L, et al. Nucleic acid delivery using magnetic nanoparticles: The magnetofection technology[J].Therapeutic Delivery,2011,2(4):471. 10 Mok H, Zhang M.Superparamagnetic iron oxide nanoparticle-based delivery systems for biotherapeutics[J].Expert Opinion on Drug Delivery,2013,10(1):73. 11 Tan Y M, Shao H P, Ji Y, et al. Preparation and research of stable Fe3O4 magnetic nanofluids in kerosene[J].Powder Metallurgy Technology,2012,30(3):163(in Chinese). 谭易明,邵慧萍,季业,等.稳定性油基纳米Fe3O4磁性流体的制备与性能研究[J].粉末冶金技术,2012,30(3):163. 12 Al-Deen F N, Ho J, Selomulya C, et al. Superparamagnetic nano-particles for effective delivery of malaria DNA vaccine[J].Langmuir,2011,27(7):3703. 13 Hsiue G H, Chiang H Z, Wang C H, et al. Nonviral gene carriers based on diblock copolymers of poly(2-ethyl-2-oxazoline) and linear polyethylenimine[J].Bioconjugate Chemistry,2006,17(3):781. 14 Xun M M, Liu Y H, Guo Q, et al. Low molecular weight PEI-appended polyesters as non-viral gene delivery vectors[J].European Journal of Medicinal Chemistry,2014,78:118. 15 Wang X, Niu D, Hu C, et al. Polyethyleneimine-based nanocarriers for gene delivery[J].Current Pharmaceutical Design,2015,21(42):6140. 16 Kim Y K, Zhang M, Lu J J, et al. PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier[J].Journal of Drug Targeting,2016,24(5):457. 17 Chen D Z, Xue W Q, Gong J, et al. Feasibility of magnetic nanoparticles modified by PEI as gene vector[J].Journal of the Fourth Military Medical University,2008(1):13(in Chinese). 陈道桢,薛文群,龚健,等.PEI-氧化铁磁性纳米颗粒作为基因载体的实验观察[J].第四军医大学学报,2008(1):13. 18 Kim M C, Lin M M, Sohn Y, et al. Polyethyleneimine-associated polycaprolactone-Superparamagnetic iron oxide nanoparticles as a gene delivery vector[J].Journal of Biomedical Materials Research Part B Applied Biomaterials,2017,105(1):145. 19 Höbel S, Aigner A. Polyethylenimines for siRNA and miRNA deli-very in vivo[J].Wiley Interdisciplinary Reviews Nanomedicine & Nanobiotechnology,2013,5(5):484. 20 Plank C, Zelphati O, Mykhaylyk O. Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-progress and prospects[J].Advanced Drug Delivery Reviews,2011,63(14-15):1300. 21 Wang C M. Tumor-targeting magnetic lipoplex delivery of shRNA suppresses IGF-IR overexpression of lung cancer A549 cells in vitro and in vivo[D].Hangzhou:Zhejiang University,2012(in Chinese). 王春茂.磁性纳米颗粒联合脂质体传递shRNA特异性抑制非小细胞肺癌生长的体内外实验研究[D].杭州:浙江大学,2012. 22 McGill S L, Cuylear C L, Adolphi N L, et al. Magnetically responsive nanoparticles for drug delivery applications using low magnetic field strengths[J].IEEE Transactions on Nanobioscience,2009,8(1):33. 23 Hasenpusch G, Geiger J, Wagner K, et al. Magnetized aerosols comprising superparamagnetic iron oxide nanoparticles improve targeted drug and gene delivery to the lung[J].Pharmaceutical Research,2012,29(5):1308. 24 He W, He X L, Xu Z, et al.The Gram-Schmidt orthogonal data fitting method for the designing of gradient magnetic field of the unila-teral NMR[J].Journal of Chonging University,2013,36(1):86(in Chinese). 何为,何晓龙,徐征,等.单边核磁共振磁体梯度磁场设计的Gram-Schmidt正交化拟合方法[J].重庆大学学报,2013,36(1):86. 25 Ma Y J. Magnetic nanoparticles: Cellular uptake and gene transfection[D].Shanghai:Shanghai Jiao Tong University,2012(in Chinese). 马勇杰.磁性纳米粒子的细胞内吞及基因转染研究[D].上海:上海交通大学,2012. 26 Deng H X, Wei Y Q. Current status, problems and prospects in gene therapy[J].Chinese Bulletin of Life Sciences,2005(3):196(in Chinese). 邓洪新,魏于全.基因治疗的发展现状、问题和展望[J].生命科学,2005(3):196.
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2018, Vol. 32 
