Controlled Release Technology Suppresses the Progression of Disseminated Pancreatic Cancer Cells

Article Preview

Abstract:

NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as a potent angiogenesis inhibitor. This study is an investigation to evaluate the feasibility of controlled release of NK4 plasmid DNA in suppressing tumor growth. Controlled release by a biodegradable hydrogel enabled the NK4 plasmid DNA to enhance the tumor suppression effects. Biodegradable microspheres of cationized gelatin were prepared for the controlled release of a NK4 plasmid DNA. The cationized gelatin microspheres incorporating NK4 plasmid DNA were subcutaneously injected to tumor-bearing mice to evaluate the suppressive effects on tumor angiogenesis and growth. The cationized gelatin microspheres incorporating NK4 plasmid DNA could release over 28 days. When the cationized gelatin microspheres incorporating NK4 plasmid DNA were injected into the subcutaneous tissue of mice intraperitoneally inoculated with pancreatic cancer cells, their survival time period was prolonged. Tumor growth was suppressed to a significantly greater extent than free NK4 plasmid DNA. The controlled release of NK4 plasmid DNA suppressed angiogenesis and increased cell apoptosis in the tumor tissue, while it enhanced and prolonged the serum level of NK4 protein. We conclude that the controlled release technology was promising to enhance the tumor suppression effects of NK4 plasmid DNA.

You might also be interested in these eBooks

Info:

Periodical:

Key Engineering Materials (Volumes 288-289)

Pages:

121-124

Citation:

Online since:

June 2005

Export:

Price:

Permissions CCC:

Permissions PLS:

Сopyright:

© 2005 Trans Tech Publications Ltd. All Rights Reserved

Share:

Citation:

[1] T. Nakamura, T. Nishizawa, M. Hagiya, T. Seki, M. Shimonishi, A. Sugimura, K. Tashiro, and S. Shimizu. Molecular cloning and expression of human hepatocyte growth factor. Nature 342: 440-443 (1989).

DOI: 10.1038/342440a0

Google Scholar

[2] R. Zarnegar, and G. K. Michalopoulos. The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis. J. Cell Biol. 129: 1177-1180 (1995).

DOI: 10.1083/jcb.129.5.1177

Google Scholar

[3] K. Matsumoto and T. Nakamura. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem. Biophys. Res. Commun. 239: 639-644 (1997).

DOI: 10.1006/bbrc.1997.7517

Google Scholar

[4] J. Cortner, G. F. Vande Woude, and S. Rong. The Met-HGF/SF autocrine signaling mechanism is involved in sarcomagenesis. EXS 74: 89-121 (1995).

DOI: 10.1007/978-3-0348-9070-0_6

Google Scholar

[5] M. Jeffers, S. Rong, and G. F. Vande Woude. Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion / metastasis. J. Mol. Med. 74: 505-513 (1996).

DOI: 10.1007/bf00204976

Google Scholar

[6] C. T. To and M. S. Tsao. The roles of hepatocyte growth factor/scatter factor and met receptor in human cancers. Oncol. Rep. 5: 1013-1024 (1998).

DOI: 10.3892/or.5.5.1013

Google Scholar

[7] W. G. Jiang, S. Hiscox, K. Matsumoto, and T. Nakamura. Hepatocyte growth factor/scatter factor, its molecular, cellular and clinical implications in cancer. Crit. Rev. Oncol. Hematol. 29: 209-248 (1999).

DOI: 10.1016/s1040-8428(98)00019-5

Google Scholar

[8] K. Date, K. Matsumoto, H. Shimura, M. Tanaka, and T. Nakamura. HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett. 420: 1-6 (1997).

DOI: 10.1016/s0014-5793(97)01475-0

Google Scholar

[9] K. Date, K. Matsumoto, K. Kuba, H. Shimura, M. Tanaka, and T. Nakamura. Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factor. Oncogene 17: 3045-3054 (1998).

DOI: 10.1038/sj.onc.1202231

Google Scholar

[10] K. Kuba, K. Matsumoto, K. Date, H. Shimura, M. Tanaka, and T. Nakamura. HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice. Cancer Res. 60: 6737-6743 (2000).

DOI: 10.1038/sj.onc.1202231

Google Scholar

[11] T. Merdan, J. Kopecek, and T. Kissel. Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv. Drug Deliv. Rev. 54: 715-758 (2002).

DOI: 10.1016/s0169-409x(02)00046-7

Google Scholar

[12] M. Matsuura, Y. Yamazaki, M. Sugiyama, M. Kondo, H. Ori, M. Nango, N. Oku. Polycation liposome-mediated gene transfer in vivo. Biochim. Biophys. Acta. 1612: 136-143 (2003).

DOI: 10.1016/s0005-2736(03)00109-3

Google Scholar

[13] A. Veis. The physical chemistry of gelatin. Int. Rev. Connect. Tissue Res. 3: 113-200 (1965).

Google Scholar

[14] Y. Tabata, Y. Ikada. Protein release from gelatin matrices. Adv. Drug Deliv. Rev. 31: 287-301 (1998).

Google Scholar

[15] Y. Fukunaka, K. Iwanaga, K. Morimoto, M. Kakemi, and Y. Tabata. Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation. J. Control. Release 80: 333-343 (2002).

DOI: 10.1016/s0168-3659(02)00026-3

Google Scholar

[16] T. Kushibiki, R. Tomoshige, Y. Fukunaka, M. Kakemi, and Y. Tabata. In vivo release and gene expression of plasmid DNA by hydrogels of gelatin with different cationization extents. J. Control. Release 90: 207-216 (2003).

DOI: 10.1016/s0168-3659(03)00197-4

Google Scholar

[17] H. Cohen, R. J. Levy, J. Gao, I. Fishbein, V. Kousaev, S. Sosnowski, S. Slomkowski, and G. Golomb. Sustained delivery and expression of DNA encapsulated in polymeric nanoparticles. Gene Ther. 7: 1896-1905 (2000).

DOI: 10.1038/sj.gt.3301318

Google Scholar

[18] C. Perez, A. Sanchez, D. Putnam, D. Ting, R. Langer, and M. J. Alonso. Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA. J. Control. Release 75: 211-224 (2001).

DOI: 10.1016/s0168-3659(01)00397-2

Google Scholar

[19] L. Holmgren, M. S. O'Reilly, and J. Folkman. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med. 1: 149-153 (1995).

DOI: 10.1038/nm0295-149

Google Scholar

[20] M. S. O'Reilly, L. Holmgren, C. Chen, and J. Folkman. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat. Med. 2: 689-692 (1996).

DOI: 10.1038/nm0696-689

Google Scholar

[21] R. Langer. Drug delivery and targeting. Nature 392S: 5-10 (1998).

Google Scholar

[22] F. D. Ledley. Pharmaceutical approach to somatic gene therapy. Pharm. Res. 13: 1595-1614 (1996).

Google Scholar

[23] W. Zauner, A. Kichler, W. Schmidt, A. Sinski, and E. Wagner. Glycerol enhancement of ligand-polylysine/DNA transfection. Biotecniques 20: 905-913 (1996).

DOI: 10.2144/96205rr04

Google Scholar

[24] P. Midoux and M. Monsigny. Efficient gene transfer by histidylated polylysine/pDNA complexes. Bioconjugate Chem. 10: 406-411 (1999).

DOI: 10.1021/bc9801070

Google Scholar