Skip to main content
SpringerLink
Log in

Polyethylenimine functionalized magnetic nanoparticles as a potential non-viral vector for gene delivery

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Polyethylenimine (PEI) functionalized magnetic nanoparticles were synthesized as a potential non-viral vector for gene delivery. The nanoparticles could provide the magnetic-targeting, and the cationic polymer PEI could condense DNA and avoid in vitro barriers. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, dynamic light scattering measurements, transmission electron microscopy, vibrating sample magnetometer and atomic force microscopy. Agarose gel electrophoresis was used to asses DNA binding and perform a DNase I protection assay. The Alamar blue assay was used to evaluate negative effects on the metabolic activity of cells incubated with PEI modified magnetic nanoparticles and their complexes with DNA both in the presence or absence of an external magnetic field. Flow cytometry and fluorescent microscopy were also performed to investigate the transfection efficiency of the DNA-loaded magnetic nanoparticles in A549 and B16-F10 tumor cells with (+M) or without (−M) the magnetic field. The in vitro transfection efficiency of magnetic nanoparticles was improved obviously in a permanent magnetic field. Therefore, the magnetic nanoparticles show considerable potential as nanocarriers for gene delivery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Yao Z, Fenoglio S, Gao DC, Camiolo M, Stiles B, Lindsted T, Schlederer M, Johns C, Altorki N, Mittal V. TGF-β IL-6 axis mediates selective and adaptive mechanisms of resistance to molecular targeted therapy in lung cancer. PANS. 2010;107:15535–40.

    Article  CAS  Google Scholar 

  2. Day ES, Morton JG, West JL. Nanoparticles for thermal cancer therapy. J Biomech Eng. 2009;131:074001.

    Article  Google Scholar 

  3. Redd WH, Montgomery GH, DuHamel KN. Behavioral intervention for cancer treatment side effects. J Natl Cancer Inst. 2001;93:810.

    Article  CAS  Google Scholar 

  4. Lungwitz U, Breunig M, Blunk T, Gopferich A. Polyethylenimine-based non-viral gene delivery systems. Eur J Pharm Biopharm. 2005;60:247–66.

    Article  CAS  Google Scholar 

  5. Godbey W, Wu KK, Mikos AG. Poly (ethylenimine) and its role in gene delivery. J Controlled Release. 1999;60:149–60.

    Article  CAS  Google Scholar 

  6. Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003;4:346–58.

    Article  CAS  Google Scholar 

  7. Jackson DA, Juranek S, Lipps HJ. Designing nonviral vectors for efficient gene transfer and long-term gene expression. Mol Ther. 2006;14:613–26.

    Article  CAS  Google Scholar 

  8. Floch V, Loisel S, Guenin E, Hervé AC, Clément JC, Yaouanc JJ, Abbayes H, Férec C. Cation substitution in cationic phosphonolipids: a new concept to improve transfection activity and decrease cellular toxicity. J Med Chem. 2000;43:4617–28.

    Article  CAS  Google Scholar 

  9. Floch V, Legros N, Loisel S, Guillaume C, Guilbot J, Benvegnu T, Ferrieres V, Plusquellec D, Ferec C. New biocompatible cationic amphiphiles derivative from glycine betaine: A novel family of efficient nonviral gene transfer agents* 1. Biochem Biophys Res Commun. 1998;251:360–5.

    Article  CAS  Google Scholar 

  10. Hobel S, Prinz R, Malek A, Urban-Klein B, Sitterberg J, Bakowsky U, Czubayko F, Aigner A. Polyethylenimine PEI F25-LMW allows the long-term storage of frozen complexes as fully active reagents in siRNA-mediated gene targeting and DNA delivery. Eur J Pharm Biopharm. 2008;70:29–41.

    Article  Google Scholar 

  11. Jiang X, Lok MC, Hennink WE. Degradable-brushed pHEMA–pDMAEMA synthesized via ATRP and click chemistry for gene delivery. Bioconjugate Chem. 2007;18:2077–84.

    Article  CAS  Google Scholar 

  12. Lin C, Zhong Z, Lok MC, Jiang X, Hennink WE, Feijen J, Engbersen JFJ. Novel bioreducible poly (amido amine)s for highly efficient gene delivery. Bioconjugate Chem. 2007;18:138–45.

    Article  CAS  Google Scholar 

  13. Fukushima S, Miyata K, Nishiyama N, Kanayama N, Yamasaki Y, Kataoka K. PEGylated polyplex micelles from triblock catiomers with spatially ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery. J Am Chem Soc. 2005;127:2810–1.

    Article  CAS  Google Scholar 

  14. Morris MC, Chaloin L, Méry J, Heitz F, Divita G. A novel potent strategy for gene delivery using a single peptide vector as a carrier. Nucleic Acids Res. 1999;27:3510–7.

    Article  CAS  Google Scholar 

  15. Morishita N, Nakagami H, Morishita R, Takeda S, Mishima F. Magnetic nanoparticles with surface modification enhanced gene delivery of HVJ-E vector. Biochem Biophys Res Commun. 2005;334:1121–6.

    Article  CAS  Google Scholar 

  16. Liu Z, Winters M, Holodniy M, Dai H. siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem. 2007;119:2069–73.

    Article  Google Scholar 

  17. Srinivasan C, Lee J, Papadimitrakopoulos F, Silbart LK, Zhao M, Burgess DJ. Labeling and intracellular tracking of functionally active plasmid DNA with semiconductor quantum dots. Mol Ther. 2006;14:192–201.

    Article  CAS  Google Scholar 

  18. Christou P, McCabe DE, Martinell BJ, Swain WF. Soybean genetic engineering-commercial production of transgenic plants. Trends Biotechnol. 1990;8:145–51.

    Article  CAS  Google Scholar 

  19. Olton D, Li J, Wilson ME, Rogers T, Close J, Huang L, Kumta PN, Sfeir C. Nanostructured calcium phosphates (NanoCaPs) for non-viral gene delivery: influence of the synthesis parameters on transfection efficiency. Biomaterials. 2007;28:1267–79.

    Article  CAS  Google Scholar 

  20. Yang J, Lee ES, Noh MY, Koh SH, Lim EK, Yoo A. Ambidextrous magnetic nanovectors for synchronous gene transfection and labeling of human MSCs. Biomaterials. 2011;32:6174–82.

    CAS  Google Scholar 

  21. Liu Y, Chen Z, Gu N, Wang J. Effects of DMSA-coated Fe (3) O (4) magnetic nanoparticles on global gene expression of mouse macrophage RAW264. 7 cells. Toxicol Lett. 2011;28:6174–82.

    Google Scholar 

  22. Lei Y, Rahim M, Ng Q, Segura T. Hyaluronic acid and fibrin hydrogels with concentrated DNA/PEI polyplexes for local gene delivery. J Controlled Release. 2011;153:255–61.

    Article  CAS  Google Scholar 

  23. Sun K, Wang J, Zhang J, Hua M, Liu C, Chen T. Dextran-g-PEI nanoparticles as a carrier for co-delivery of adriamycin and plasmid into osteosarcoma cells. Int J Biol Macromol. 2011;49:173–80.

    Article  CAS  Google Scholar 

  24. Neu M, Fischer D, Kissel T. Recent advances in rational gene transfer vector design based on poly (ethylene imine) and its derivatives. J Gene Med. 2005;5:992–1009.

    Article  Google Scholar 

  25. Ragusa A, García I, Penadés S. Nanoparticles as nonviral gene delivery vectors. IEEE Trans Nanobioscience. 2007;6:319–30.

    Article  Google Scholar 

  26. Lübbe AS, Alexiou C, Bergemann C. Clinical applications of magnetic drug targeting. J Surg Res. 2001;95:200–6.

    Article  Google Scholar 

  27. Bae KH, Choi SH, Park SY, Lee Y, Park TG. Thermosensitive pluronic micelles stabilized by shell cross-linking with gold nanoparticles. Langmuir. 2006;22:6380–4.

    Article  CAS  Google Scholar 

  28. Lu J, Ma S, Sun J, Xia C, Liu C, Wang Z, Zhao X, Gao F, Gong Q, Song B. Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging. Biomaterials. 2009;30:2919–28.

    Article  CAS  Google Scholar 

  29. Lee PW, Hsu SH, Wang JJ, Tsai JS, Lin KJ, Wey SP, Chen FR, Lai CH, Yen TC. Sung H W: The characteristics, biodistribution, magnetic resonance imaging and biodegradability of superparamagnetic core-shell nanoparticles. Biomaterials. 2010;31:1316–24.

    Article  CAS  Google Scholar 

  30. Chen D, Jiang M, Li N, Gu H, Xu Q, Ge J, Xia X, Lu J. Modification of magnetic silica/iron oxide nanocomposites with fluorescent polymethacrylic acid for cancer targeting and drug delivery. J Mater Chem. 2010;20:6422–9.

    Article  CAS  Google Scholar 

  31. Hong R, Fischer NO, Emrick T, Rotello VM. Surface PEGylation and ligand exchange chemistry of FePt nanoparticles for biological applications. Chem Mater. 2005;17:4617–21.

    Article  CAS  Google Scholar 

  32. Huang C, Zhou YB, Jin Y, Zhou X, Tang ZM, Guo X, Zhou SB. Preparation and characterization of temperature-responsive and magnetic nanomicelles. J Mater Chem. 2011;21:5660–7.

    Article  CAS  Google Scholar 

  33. Sun J, Zhou SB, Hou P, Yang Y, Weng J, Li XH, Li MY. Synthesis and characterization of biocompatible Fe3O4 nanoparticles. J Biomed Mater Res A. 2007;80:333–41.

    Google Scholar 

  34. Kobayashi M, Ryosuke M, Hideyuki O, Atsushi T. Precise surface structure control of inorganic solid and metal oxide nanoparticles through surface-initiated radical polymerization. Sci Technol Adv Mater. 2006;7:617–28.

    Article  CAS  Google Scholar 

  35. Wang L, Neoh KN, Kang ET, Shuter B, Wang SC. Biodegradable magnetic-fluorescent magnetite/poly(DL-lactic acid-co-a, b-malic acid) composite nanoparticles for stem cell labeling. Biomaterials. 2010;31:3502–11.

    Article  CAS  Google Scholar 

  36. Kim MS, Chen YF, Liu YC, Peng XG. Super-stable, high-quality Fe3O4 dendron-nanocrystals dispersible in both organic and aqueous solutions. Adv Mater. 2005;17:1429–32.

    Article  CAS  Google Scholar 

  37. Lee JH, Lee KR, Moon SH, Lee YH, Park TG, Cheon JW. All-in-one target-cell-specific magnetic nanoparticles for simultaneous molecular imaging and siRNA delivery. Angew Chem Int Ed. 2009;121:4238–43.

    Article  Google Scholar 

  38. Shi S, Guo QF, Kan B, Fu SZ, Wang XH, Gong CY, Deng HX, Luo F, Zhao X, Wei YQ. A novel poly (ε-caprolactone)-pluronic-poly (ε-caprolactone) grafted polyethyleneimine (PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study. BMC Biotechnol. 2009;9:65.

    Article  Google Scholar 

  39. Lu X, Wang QQ, Xu FJ, Tang GP, Yang WT. A cationic prodrug/therapeutic gene nanocomplex for the synergistic treatment of tumors. Biomaterials. 2011;32:4849–56.

    Article  CAS  Google Scholar 

  40. Mikhaylova M, Kim DK, Bobrysheva N, Osmolowsky M, Semenov V. Superparamagnetism of magnetite nanoparticles: dependence on surface modification. Langmuir. 2004;20:2472–7.

    Article  CAS  Google Scholar 

  41. Huang FW, Wang HY, Li C, Wang HF, Sun YX, Feng J, Zhang XZ, Zhuo RX. PEGylated PEI-based biodegradable polymers as non-viral gene vectors. Acta Biomater. 2010;6:4285–95.

    Article  CAS  Google Scholar 

  42. Xenariou S, Griesenbach U, Ferrari S, Dean P, Scheule R, Cheng S, Geddes D, Plank C, Alton E. Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo. Gene Ther. 2006;13:1545–52.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by National Basic Research Program of China (973 Program, 2012CB933602), National Natural Science Foundation of China (No. 30970723 and No. 51173150), Fundamental Research Funds for the Central Universities (SWJTU11ZT10) and the Open Research Fund of the Key Laboratory of Biotherapy, West China Hospital, West China Medicine School, Sichuan University under Grant No. SKLB200907.

Author information

Authors and Affiliations

  1. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, People’s Republic of China

    Yangbo Zhou, Chunli Shi & Shaobing Zhou

  2. School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, People’s Republic of China

    Zhaomin Tang & Shaobing Zhou

  3. State Key Laboratory of Biotherapy, West China Hospital, West China Medicine School, Sichuan University, Chengdu, 610041, People’s Republic of China

    Shuai Shi & Zhiyong Qian

Authors
  1. Yangbo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhaomin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chunli Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shuai Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhiyong Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shaobing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaobing Zhou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, Y., Tang, Z., Shi, C. et al. Polyethylenimine functionalized magnetic nanoparticles as a potential non-viral vector for gene delivery. J Mater Sci: Mater Med 23, 2697–2708 (2012). https://doi.org/10.1007/s10856-012-4720-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4720-5

Keywords

Search

Navigation