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Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery

Abstract

Dendritic cells (DC) targeting vaccines require high efficiency for uptake, followed by DC activation and maturation. We used magnetic vectors comprising polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles, with hyaluronic acid (HA) of different molecular weights (<10 and 900 kDa) to reduce cytotoxicity and to facilitate endocytosis of particles into DCs via specific surface receptors. DNA encoding Plasmodium yoelii merozoite surface protein 1–19 and a plasmid encoding yellow fluorescent gene were added to the magnetic complexes with various % charge ratios of HA: PEI. The presence of magnetic fields significantly enhanced DC transfection and maturation. Vectors containing a high-molecular-weight HA with 100% charge ratio of HA: PEI yielded a better transfection efficiency than others. This phenomenon was attributed to their longer molecular chains and higher mucoadhesive properties aiding DNA condensation and stability. Insights gained should improve the design of more effective DNA vaccine delivery systems.

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References

  1. Liu MA . DNA vaccines: an historical perspective and view to the future. Immunol Rev 2011; 239: 62–84.

    Article  CAS  Google Scholar 

  2. Seder RA, Hill AVS . Vaccines against intracellular infections requiring cellular immunity. Nature 2000; 406: 793–798.

    Article  CAS  Google Scholar 

  3. Park TG, Jeong JH, Kim SW . Current status of polymeric gene delivery systems. Adv Drug Deliv Rev 2006; 58: 467–486.

    Article  CAS  Google Scholar 

  4. Liu S, Danquah MK, Ho J, Ma C, Wang L, Coppel R et al. Preparation and characterization of poly(lactic-co-glycolic acid) microparticles containing DNA molecules encoding a malaria vaccine candidate. J Chem Technol Biotechnol 2009; 84: 782–788.

    Article  CAS  Google Scholar 

  5. Liu S, Danquah MK, Forde GM, Ma C, Wang L, Coppel R . Microparticle-mediated gene delivery for the enhanced expression of a 19-KDa fragment of merozoite surface protein 1 of Plasmodium falciparum. Biotechnol Prog 2010; 26: 257–262.

    Article  CAS  Google Scholar 

  6. Al-Deen FN, Ho J, Selomulya C, Ma C, Coppel R . Superparamagnetic nanoparticles for effective delivery of malaria DNA vaccine. Langmuir 2011; 27: 3703–3712.

    Article  CAS  Google Scholar 

  7. Xiang SD, Scalzo-Inguanti K, Minigo G, Park A, Hardy CL, Plebanski M . Promising particle-based vaccines in cancer therapy. Expert Rev Vaccines 2008; 7: 1103–1119.

    Article  Google Scholar 

  8. Hamm A, Krott N, Breibach I, Blindt R, Bosserhoff AK . Efficient transfection method for primary cells. Tissue Engineering 2002; 8: 235–245.

    Article  CAS  Google Scholar 

  9. Chapman SWK, Hassa PO, Koch-Schneidemann S, von Rechenberg B, Hofmann-Amtenbrink M, Steitz B et al. Application of pulsed-magnetic field enhances non-viral gene delivery in primary cells from different origins. J Magn Magn Mater 2008; 320: 1517–1527.

    Article  Google Scholar 

  10. Tang RP, Palumbo RN, Nagarajan L, Krogstad E, Wang C . Well-defined block copolymers for gene delivery to dendritic cells: Probing the effect of polycation chain-length. J Control Release 2010; 142: 229–237.

    Article  CAS  Google Scholar 

  11. Necas J, Bartosikova L, Brauner P, Kolar J . Hyaluronic acid (hyaluronan): a review. Veterinarni Medicina 2008; 53: 397–411.

    Article  CAS  Google Scholar 

  12. Oh EJ, Park K, Kim KS, Kim J, Yang JA, Kong JH et al. Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives. J Control Release 2010; 141: 2–12.

    Article  CAS  Google Scholar 

  13. Godbey WT, Wu KK, Mikos AG . Poly(ethylenimine) and its role in gene delivery. J Control Release 1999; 60: 149–160.

    Article  CAS  Google Scholar 

  14. Al-Deen FN, Selomulya C, Williams T . On designing stable magnetic vectors as carriers for malaria DNA vaccine. Colloids Interfaces B: Biointerfaces 2012; 102: 492–503.

    Article  Google Scholar 

  15. Plank C, Schillinger U, Scherer F, Bergemann C, Remy JS, Krotz F et al. The magnetofection method: Using magnetic force to enhance gene delivery. Biol Chem 2003; 384: 737–747.

    Article  CAS  Google Scholar 

  16. Scherer F, Anton M, Schillinger U, Henkel J, Bergemann C, Kruger A et al. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther 2002; 9: 102–109.

    Article  CAS  Google Scholar 

  17. Hartmann G, Weiner GJ, Krieg AM . CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells. Proc Natl Acad Sci USA 1999; 96: 9305–9310.

    Article  CAS  Google Scholar 

  18. Spies B, Hochrein H, Vabulas M, Huster K, Busch DH, Schmitz F et al. Vaccination with plasmid DNA activates dendritic cells via toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice. J Immunol 2003; 171: 5908–5912.

    Article  CAS  Google Scholar 

  19. Liao YH, Jones SA, Forbes B, Martin GP, Brown MB . Hyaluronan: pharmaceutical characterization and drug delivery. Drug Delivery 2005; 12: 327–342.

    Article  CAS  Google Scholar 

  20. Lim ST, Forbes B, Berry DJ, Martin GP, Brown MB . In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits. Int J Pharm 2002; 231: 73–82.

    Article  CAS  Google Scholar 

  21. Laurent TC, Fraser JRE, Pertoft H, Smedsrod B . Binding of hyaluronate and chondroitin sulfate to liver endothelial-cells. Biochem J 1986; 234: 653–658.

    Article  CAS  Google Scholar 

  22. Wolny PM, Banerji S, Gounou C, Brisson AR, Day AJ, Jackson DG et al. Analysis of cd44-hyaluronan interactions in an artificial membrane system insights into the distinct binding properties of high and low molecular weight hyaluronan. J Biol Chem 2010; 285: 30170–30180.

    Article  CAS  Google Scholar 

  23. Yao J, Fan Y, Du RH, Zhou JP, Lu Y, Wang W et al. Amphoteric hyaluronic acid derivative for targeting gene delivery. Biomaterials 2010; 31: 9357–9365.

    Article  CAS  Google Scholar 

  24. Qhattal HSS, Liu XL . Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes. Mol Pharm 2011; 8: 1233–1246.

    Article  CAS  Google Scholar 

  25. Do Y, Nagarkatti PS, Nagarkatti M . Role of CD44 and hyaluronic acid (HA) in activation of alloreactive and antigen-specific T cells by bone marrow-derived dendritic cells. J Immunother 2004; 27: 1–12.

    Article  CAS  Google Scholar 

  26. Banchereau J, Steinman RM . Dendritic cells and the control of immunity. Nature 1998; 392: 245–252.

    Article  CAS  Google Scholar 

  27. Watts C . Capture and processing of exogenous antigens for presentation on MHC molecules. Ann Rev Immunol 1997; 15: 821–850.

    Article  CAS  Google Scholar 

  28. Kim A, Checkla DM, Dehazya P, Chen WL . Characterization of DNA-hyaluronan matrix for sustained gene transfer. J Contro Release 2003; 90: 81–95.

    Article  CAS  Google Scholar 

  29. Hamilton JA, Anderson GP . GM-CSF biology. Growth Factors 2004; 22: 225–231.

    Article  CAS  Google Scholar 

  30. Ali OA, Mooney DJ . Sustained GM-CSF and PEI condensed pDNA presentation increases the level and duration of gene expression in dendritic cells. J Control Release 2008; 132: 273–278.

    Article  CAS  Google Scholar 

  31. Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF . Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 2008; 38: 1404–1413.

    Article  CAS  Google Scholar 

  32. Ito T, Iida-Tanaka N, Niidome T, Kawano T, Kubo K, Yoshikawa K et al. Hyaluronic acid and its derivative as a multi-functional gene expression enhancer: protection from non-specific interactions, adhesion to targeted cells, and transcriptional activation. J Control Release 2006; 112: 382–388.

    Article  CAS  Google Scholar 

  33. Culty M, Nguyen HA, Underhill CB . The hyaluronan receptor (cd44) participates in the uptake and degradation of hyaluronan. J Cell Biol 1992; 116: 1055–1062.

    Article  CAS  Google Scholar 

  34. Kaya G, Augsburger E, Stamenkovic I, Saurat JH . Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus. J Invest Dermatol 2000; 115: 1054–1058.

    Article  CAS  Google Scholar 

  35. Garg HG, Hales CA . Chemistry and Biology of Hyaluronan. Elsevier Ltd.: Oxford, UK, 2004.

    Google Scholar 

  36. Weigel JA, Raymond RC, Weigel PH . The hyaluronan receptor for endocytosis (HARE) is not CD44 or CD54 (ICAM-1). Biochem Biophys Res Commun 2002; 294: 918–922.

    Article  CAS  Google Scholar 

  37. Termeer CC, Hennies J, Voith U, Ahrens T, Weiss JM, Prehm P et al. Oligosaccharides of hyaluronan are potent activators of dendritic cells. J Immunol 2000; 165: 1863–1870.

    Article  CAS  Google Scholar 

  38. Inaba K, Inaba M, Deguchi M, Hagi K, Yasumizu R, Ikehara S et al. Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class-ii-negative progenitor in mouse bone-marrow. Proc Natl Acad Sci USA 1993; 90: 3038–3042.

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge Dr Tim Williams from the Monash Centre of Electron Microscopy for assistance in TEM imaging.

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Correspondence to C Selomulya.

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Nawwab AL-Deen, F., Selomulya, C., Kong, Y. et al. Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery. Gene Ther 21, 212–218 (2014). https://doi.org/10.1038/gt.2013.77

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