Targeted CRM197-PEG-PEI/siRNA complexes for Therapeutic RNAi in Glioblastoma

Pharmaceuticals

Volumn 4, Issue 12, 2011, Pages 1591-1606

  Höbel, Sabrina ^a,b   Appeldoorn, Chantal C M ^c   Gaillard, Pieter J ^c   Aigner, Achim ^a,b  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b Rudolf Boehm Institute of Pharmacology and Toxicology   (Germany)

^c Bio Partner Center II   (Netherlands)

Author keywords

CRM197; Glioblastoma; HB EGF; PEI; Pleiotrophin; Polyethylenimine; RNA interference; RNAi; SiRNA; Targeted delivery; Therapeutic siRNA delivery

Indexed keywords

DIPHTHERIA TOXOID CRM197; MACROGOL; PLEIOTROPHIN; POLYETHYLENEIMINE; SMALL INTERFERING RNA;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL CULTURE; CONTROLLED STUDY; DRUG DELIVERY SYSTEM; GENE; GENE OVEREXPRESSION; GENE SILENCING; GLIOBLASTOMA; MOLECULAR SIZE; MOLECULAR STABILITY; MOUSE; NONHUMAN; PLEIOTROPHIN GENE; REPORTER GENE; RNA INTERFERENCE; TUMOR XENOGRAFT; ZETA POTENTIAL;

EID: 84855267588     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph4121591     Document Type: Article

References (49)

1. Fire, A.; Xu, S.; Montgomery, M.K.; Kostas, S.A.; Driver, S.E.; Mello, C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 391, 806-811.
2. Elbashir, S.M.; Lendeckel, W.; Tuschl, T. RNA interference is mediated by 21-and 22-nucleotide RNAs. Genes Dev. 2001, 15, 188-200.
3. Aigner, A. Applications of RNA interference: Current state and prospects for siRNA-based strategies in vivo. Appl. Microbiol. Biotechnol. 2007, 76, 9-21.
4. Boussif, O.; Lezoualch, F.; Zanta, M.A.; Mergny, M.D.; Scherman, D.; Demeneix, B.; Behr, J.P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethyleneimine. Proc. Nat. Acad. Sci. USA 1995, 92, 7297-7301.
5. Erbacher, P.; Bettinger, T.; Brion, E.; Coll, J.L.; Plank, C.; Behr, J.P.; Remy, J.S. Genuine DNA/polyethylenimine (PEI) complexes improve transfection properties and cell survival. J. Drug Target. 2004, 12, 223-236.
6. Behr, J.P. The proton sponge: A trick to enter cells the viruses did not exploit. Chimia 1997, 51, 34-36.
7. Aigner, A.; Fischer D.; Merdan, T.; Brus, C.; Kissel, T.; Czubayko, F. Delivery of unmodified bioactive ribozymes by an RNA-stabilizing polyethylenimine (LMW-PEI) efficiently down-regulates gene expression. Gene Ther. 2002, 7, 1700-1707.
8. Urban-Klein, B.; Werth, S.; Abuharbeid, S.; Czubayko, F.; Aigner, A. RNAi-mediated gene targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther. 2005, 12, 461-466.
9. Höbel, S.; Koburger, I.; John, M.; Czubayko, F.; Hadwiger, P.; Vornlocher, H.P.; Aigner, A. Polyethylenimine/small interfering RNA-mediated knockdown of vascular endothelial growth factor in vivo exerts anti-tumor effects synergistically with Bevacizumab. J. Gene Med. 2010, 12, 287-300.
10. Ibrahim, A.F.; Weirauch, U.; Thomas, M.; Grünweller, A.; Hartmann, R.K.; Aigner, A. MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res. 2011, 71, 5214-5224.
11. Werth, S.; Urban-Klein, B.; Dai, L.; Höbel, S.; Grzelinski, M.; Bakowsky, U.; Czubayko, F.; Aigner, A. A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes. J. Control. Release 2006, 112, 257-270.
12. Stoica, G.E.; Kuo, A.; Aigner, A.; Sunitha, I.; Souttou, B.; Malerczyk, C.; Caughey, D.J.; Wen, D.; Karavanov, A.; Riegel, A.T.; et al. Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin. J. Biol. Chem. 2001, 276, 16772-16779.
13. Vanderwinden, J.M.; Mailleux, P.; Schiffmann, S.N.; Vanderhaeghen, J.J. Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues. Anat. Embryol. (Berl.) 1992, 186, 387-406.
14. Kadomatsu, K.; Muramatsu, T. Midkine and pleiotrophin in neural development and cancer. Cancer Lett. 2004, 204, 127-143.
15. Zhang, Y.; Zhang, Y.F.; Bryant, J.; Charles, A.; Boado, R.J.; Pardridge, W.M. Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer. Clin. Cancer Res. 2004, 10, 3667-3677.
16. Aigner, A.; Brachmann, P.; Beyer, J.; Jäger, R.; Raulais, D.; Vigny, M.; Neubauer, A.; Heidenreich, A.; Weinknecht, S.; Czubayko, F.; et al. Marked increase of the growth factors pleiotrophin and fibroblast growth factor-2 in serum of testicular cancer patients. Ann. Oncol. 2003, 14, 1525-1529.
17. Fang, W.; Hartmann, N.; Chow, D.T.; Riegel, A.T.; Wellstein, A. Pleiotrophin stimulates fibroblasts and endothelial and epithelial cells and is expressed in human cancer. J. Biol. Chem. 1992, 267, 25889-25897.
18. Czubayko, F.; Schulte, A.M.; Berchem, G.J.; Wellstein, A. Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin. Proc. Natl. Acad. Sci. USA 1996, 93, 14753-14758.
19. Weber, D.; Klomp, H.J.; Czubayko, F.; Wellstein, A.; Juhl, H. Pleiotrophin can be rate-limiting for pancreatic cancer cell growth. Cancer Res. 2000, 60, 5284-5288.
20. Grzelinski, M.; Bader, N.; Czubayko, F.; Aigner, A. Ribozyme-targeting reveals the rate-limiting role of pleiotrophin in glioblastoma. Int. J. Cancer 2005, 117, 942-951.
21. Grzelinski, M.; Urban-Klein, B.; Martens, T.; Lamszus, K.; Bakowsky, U.; Höbel, S.; Czubayko, F.; Aigner, A. RNA interference-mediated gene silencing of pleiotrophin through polyethylenimine-complexed small interfering RNAs in vivo exerts antitumoral effects in glioblastoma xenografts. Hum. Gene Ther. 2006, 17, 751-766.
22. Grzelinski, M.; Steinberg, F.; Martens, T.; Czubayko, F.; Lamszus, K.; Aigner, A. Enhanced antitumorigenic effects in glioblastoma on double targeting of pleiotrophin and its receptor ALK. Neoplasia 2009, 11, 145-156.
23. Raab, G.; Klagsbrun, M. Heparin-binding EGF-like growth factor. Biochim. Biophys. Acta 1997, 1333, F179-F199.
24. Mishima, K.; Higashiyama, S.; Asai, A.; Yamaoka, K.; Nagashima, Y.; Taniguchi, N.; Kitanaka, C.; Kirino, T.; Kuchino, Y. Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas. Acta Neuropathol. 1998, 96, 322-328.
25. Anderson, P. Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the nontoxic protein CRM197. Infect. Immun. 1983, 39, 233-238.
26. Gaillard, P.J.; Brink, A.; de Boer, A.G. Diphteria toxin receptor-targeted brain drug delivery. Int. Congr. Ser. 2005b, 1277, 185-198.
27. Gaillard, P.J.; de Boer, A.G. A novel opportunity for targeted drug delivery to the brain. J. Control. Release 2006, 116, e60-e62.
28. Moya, M.; Dautry-Varsat, A.; Goud, B.; Louvard, D.; Boquet, P. Inhibition of coated pit formation in Hep2 cells blocks the cytotoxicity of diphtheria toxin but not that of ricin toxin. J. Cell Biol. 1985, 101, 548-559.
29. Malek, A.; Czubayko, F.; Aigner, A. PEG grafting of polyethylenimine (PEI) exerts different effects on DNA transfection and siRNA-induced gene targeting efficacy. J. Drug Target. 2008, 16, 124-139.
30. Höbel, 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.
31. de Boer, A.G.; Gaillard, P.J. Drug targeting to the brain. Annu. Rev. Pharmacol. Toxicol. 2007, 47, 323-355.
32. Wagner, E.; Kircheis, R.; Walker, G.F. Targeted nucleic acid delivery into tumors: New avenues for cancer therapy. Biomed. Pharmacother. 2004, 58, 152-161.
33. Fischer, D.; Bieber, T.; Li, Y.; Elsässer, H.P.; Kissel, T. A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: Effect of molecular weight on transfection efficiency and cytotoxicity. Pharm. Res. 1999, 16, 1273-1279.
34. Gosselin, M.A.; Guo, W.; Lee, R.J. Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjug. Chem. 2001, 12, 989-994.
35. Chollet, P.; Favrot, M.; Hurbin, A.; Coll, J. Side-effects of a systemic injection of linear polyethylenimine-DNA complexes. J. Gene Med. 2002, 4, 84-91.
36. Moghimi, S.M.; Symonds, P.; Murray, J.C.; Hunter, A.C.; Debska, G.; Szewczyk, A. A two-stage poly(ethylenimine)-mediated cytotoxicity: Implications for gene transfer/therapy. Mol. Ther. 2005, 11, 990-995.
37. Beyerle, A.; Höbel, S.; Czubayko, F.; Schulz, H.; Kissel, T.; Aigner, A.; Stoeger, T. In vitro cytotoxic and immunomodulatory profiling of low molecular weight polyethylenimines for pulmonary application. Toxicol. In Vitro 2009, 23, 500-508.
38. Gaillard, P.J.; Visser, C.C.; de Boer, A.G. Targeted delivery across the blood-brain barrier. Expert Opin. Drug Deliv. 2005, 2, 299-309.
39. Mitamura, T.; Higashiyama, S.; Taniguchi, N.; Klagsbrun, M.; Mekada, E. Diphtheria toxin binds to the epidermal growth factor (EGF)-like domain of human heparin-binding EGF-like growth factor/diphtheria toxin receptor and inhibits specifically its mitogenic activity. J. Biol. Chem. 1995, 270, 1015-1019.
40. Prenzel, N.; Zwick, E.; Daub, H.; Leserer, M.; Abraham, R.; Wallasch, C.; Ullrich, A. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 1999, 402, 884-888.
41. Miyamoto, S.; Hirata, M.; Yamazaki, A.; Kageyama, T.; Hasuwa, H.; Mizushima, H.; Tanaka, Y.; Yagi, H.; Sonoda, K.; Kai, M.; et al. Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy. Cancer Res. 2004, 64, 5720-5727.
42. Kageyama, T.; Ohishi, M.; Miyamoto, S.; Mizushima, H.; Iwamoto, R.; Mekada, E. Diphtheria toxin mutant CRM197 possesses weak EF2-ADP-ribosyl activity that potentiates its anti-tumorigenic activity. J. Biochem. 2007, 142, 95-104.
43. Buzzi, S.; Rubboli, D.; Buzzi, G.; Buzzi, A.M.; Morisi, C.; Pironi, F. CRM197 (nontoxic diphtheria toxin): Effects on advanced cancer patients. Cancer Immunol. Immunother. 2004, 53, 1041-1048.
44. Kaestner, P.; Aigner, A.; Bastians, H. Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo. Cancer Lett. 2011, 304, 128-136.
45. Schulze, D.; Plohmann, P.; Höbel, S.; Aigner, A. Anti-tumor effects of fibroblast growth factor-binding protein (FGF-BP) knockdown in colon carcinoma. Mol. Cancer 2011, 10, 144.
46. Kircheis, R.; Wightman, L.; Wagner, E. Design and gene delivery activity of modified polyethylenimines. Adv. Drug Deli. Rev. 2001, 53, 341-358.
47. Harris, J.M.; Chess, R.B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2003, 2, 214-221.
48. Rejman, J.; Oberle, V.; Zuhorn, I.S.; Hoekstra, D. Size-dependent internalization of particles via the pathways of clathrin and caveolae-mediated endocytosis. Biochem. J. 2004, 377, 159-169.
49. Ogris, M.; Steinlein, P.; Carotta, S.; Brunner, S.; Wagner, E. DNA/polyethylenimine transfection particles: Influence of ligands, polymer size, and PEGylation on internalization and gene expression. AAPS PharmSci. 2001, 3, E21.