Progress in the design of gene delivery system is vital for cancer gene therapy since many physiological and intracellular barriers remain. We have developed a technology for condensing genes into nanometric delivery systems. In this paper, we present a novel strategy for decorating 30 nm DNA particles with folic acid for cancer cell recognition. Physicochemical and biological experiments show that these DNA complexes selectively bind to cells expressing the corresponding folic acid receptor.
NeuM., FischerD., and KisselT.Recent Advances in Rational Gene Transfer Vector Design Based on Poly(ethylene imine) and Its Derivatives. J. Gene Med.7, 992–1009 (2005).
3.
MartinB., SainlosM., AissaouiA., OudrhiriN., HauchecorneM., VigneronJ. P., LehnJ. M., and LehnP.The Design of Cationic Lipids for Gene Delivery. Curr. Pharm. Des.11, 375–394 (2005).
4.
BarronL. G., GagneL., and SzokaF. C.Jr.. Lipoplex-mediated Gene Delivery to the Lung Occurs Within 60 Minutes of Intravenous Administration. Hum. Gene Ther.10, 1683–1694 (1999).
5.
KlinkD., SchindelhauerD., LanerA., TuckerT., BebokZ., SchwiebertE. M., BoydA. C., and ScholteB. J.Gene Delivery Systems-Gene Therapy Vectors for Cystic Fibrosis. J. Cyst Fibros. 3 Suppl.2, 203–212 (2004).
6.
ZouS. M., ErbacherP., RemyJ. S., and BehrJ. P.Systemic Linear Polyethylenimine (L-PEI)-mediated Gene Delivery in the Mouse. J. Gene Med.2, 128–134 (2000).
7.
LemkineG. F., ManteroS., MigneC., RajiA., GoulaD., NormandieP., LeviG., and DemeneixB. A.Preferential Transfection of Adult Mouse Neural Stem Cells and Their Immediate Progeny In Vivo with Polyethylenimine. Molecular and Cellular Neuroscience, 165–174 (2002).
8.
JiaS. F., WorthL. L., DensmoreC. L., XuB., DuanX., and KleinermanE. S.Aerosol Gene Therapy with PEI: IL-12 Eradicates Osteosarcoma Lung Metastases. Clin. Cancer Res.9, 3462–3468 (2003).
9.
OhanaP., GofritO., AyeshS., Al-SharefW., MizrahiA., BirmanT., SchneiderT., MatoukI., GrootN., TavdyE., SidiA. A., and HochbergA.Regulatory Sequences of the H19 Gene in DNA Based Therapy of Bladder Cancer. Gene Therapy and Molecular Biology8, 181–192 (2004).
10.
LiuG., LiD., PasumarthyM. K., KowalczykT. H., GedeonC. R., HyattS. L., PayneJ. M., MillerT. J., BrunovskisP., FinkT. L., MuhammadO., MoenR. C., HansonR. W., and CooperM. J.Nanoparticles of Compacted DNA Transfect Postmitotic Cells. J. Biol. Chem.278, 32578–32586 (2003).
11.
KonstanM. W., DavisP. B., WagenerJ. S., HilliardK. A., SternR. C., MilgramL. J., KowalczykT. H., HyattS. L., FinkT. L., GedeonC. R., OetteS. M., PayneJ. M., MuhammadO., ZiadyA. G., MoenR. C., and CooperM. J.Compacted DNA Nanoparticles Administered to the Nasal Mucosa of Cystic Fibrosis Subjects are Safe and Demonstrate Partial to Complete Cystic Fibrosis Transmembrane Regulator Reconstitution. Hum. Gene Ther.15, 1255–1269 (2004).
12.
MaedaH., WuJ., SawaT., MatsumuraY., and HoriK.Tumor Vascular Permeability and the EPR Effect in Macromolecular Therapeutics: A Review. J. Control Release65, 271–284 (2000).
13.
KircheisR., WightmanL., SchreiberA., RobitzaB., RosslerV., KursaM., and WagnerE.Polyethylenimine/DNA Complexes Shielded by Transferrin Target Gene Expression to Tumors After Systemic Application. Gene Ther.8, 28–40 (2001).
14.
BarronL. G., MeyerK. B., and SzokaF. C.Jr.. Effects of Complement Depletion on the Pharmacokinetics and Gene Delivery Mediated by Cationic Lipid-DNA Complexes. Hum. Gene Ther.9, 315–323 (1998).
15.
CholletP., FavrotM. C., HurbinA., and CollJ. L.Side-effects of a Systemic Injection of Linear Polyethylenimine-DNA Complexes. J. Gene Med.4, 84–91 (2002).
16.
HanS., MahatoR. I., SungY. K., and KimS. W.Development of Biomaterials for Gene Therapy. Mol. Ther.2, 302–317 (2000).
17.
OupickyD., ParkerA. L., and SeymourL. W.Laterally Stabilized Complexes of DNA with Linear Reducible Polycations: Strategy for Triggered Intracellular Activation of DNA Delivery Vectors. J. Am. Chem. Soc.124, 8–9 (2002).
18.
BoeckleS., von GersdorffK., van der PiepenS., CulmseeC., WagnerE., and OgrisM.Purification of Polyethylenimine Polyplexes Highlights the Role of Free Polycations in Gene Transfer. J. Gene Med.6, 1102–1111 (2004).
19.
VerkmanA. S.Solute and Macromolecule Diffusion in Cellular Aqueous Compartments. Trends Biochem. Sci.27, 27–33 (2002).
20.
BlessingT., RemyJ. S., and BehrJ. P.Monomolecular Collapse of Plasmid DNA into Stable Virus-like Particles. Proc. Natl. Acad. Sci. USA95, 1427–1431 (1998).
21.
DautyE., RemyJ. S., BlessingT., and BehrJ. P.Dimerizable Cationic Detergents with a Low cmc Condense Plasmid DNA into Nanometric Particles and Transfect Cells in Culture. J. Am. Chem Soc.123, 9227–34 (2001).
22.
ZuberG.Nanoparticules d'ADN. Biofutur, 46 (2004).
23.
ZuberG., DautyE., NothisenM., BelguiseP., and BehrJ. P.Towards Synthetic Viruses. Adv. Drug Deliv. Rev.52, 245–253 (2001).
24.
ChittimallaC., Zammut-ItalianoL., ZuberG., and BehrJ. P.Monomolecular DNA Nanoparticles for Intravenous Delivery of Genes. J. Am. Chem. Soc.127, 11436–41 (2005).
25.
BlessingT., RemyJ.-S., and BehrJ.-P.Template Oligomerization of DNA-Bound Cations Produces Calibrated Nanometric Particles. J. Am. Chem. Soc.120, 8519–8520 (1998).
26.
LiW., HuangZ., MacKayJ. A., GrubeS., and SzokaF. C.Jr.. Low-pH-sensitive Poly(ethylene glycol) (PEG)-stabilized Plasmid Nanolipoparticles: Effects of PEG Chain Length, Lipid Composition and Assembly Conditions on Gene Delivery. J. Gene Med.7, 67–79 (2005).
27.
WongJ. Y., KuhlT. L., IsraelachviliJ. N., MullahN., and ZalipskyS.Direct Measurement of a Tethered Ligand-receptor Interaction Potential. Science275, 820–822. (1997).
28.
PelkmansL., KartenbeckJ., and HeleniusA.Caveolar Endocytosis of Simian Virus 40 Reveals a New Two-step Vesicular-transport Pathway to the ER. Nat. Cell Biol.3, 473–483 (2001).
29.
ChanS. Y., EmpigC. J., WelteF. J., SpeckR. F., SchmaljohnA., KreisbergJ. F., and GoldsmithM. A.Folate Receptor-alpha is a Cofactor for Cellular Entry by Marburg and Ebola Viruses. Cell106, 117–126 (2001).
30.
DautyE., RemyJ.-S., ZuberG., and BehrJ.-P.Intracellular Delivery of Nanometric DNA Particles Via the Folate Receptor. Bioconjugate Chemistry13, 831–839 (2002).
31.
ZuberG., Zammut-ItalianoL., DautyE., and BehrJ. P.Targeted Gene Delivery to Cancer Cells: Directed Assembly of Nanometric DNA Particles Coated with Folic Acid. Angew. Chem. Int. Ed.42, 2666–2669 (2003).
32.
Labat-MoleurF., SteffanA. M., BrissonC., PerronH., FeugeasO., FurstenbergerP., OberlingF., BrambillaE., and BehrJ. P.An Electron Microscopy Study into the Mechanism of Gene Transfer with Lipopolyamines. Gene Ther.3, 1010–1017 (1996).
33.
LeamonC. P. and LowP. S.Delivery of Macromolecules into Living Cells: A Method that Exploits Folate Receptor Endocytosis. Proc. Natl. Acad. Sci. USA88, 5572–5576 (1991).
34.
WangS. and LowP. S.Folate-mediated Targeting of Antineoplastic Drugs, Imaging Agents, and Nucleic Acids to Cancer Cells. J. Control Release53, 39–48 (1998).
