Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker.

Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker. Research Abstract Details 

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Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker. Abstract Text:

Kayoko Nakamura,Yi Wang,Xinrong Liu,Atsushi Kubo,Donald J Hnatowich,Kayoko Nakamura,Yi Wang,Xinrong Liu,Atsushi Kubo,Donald J Hnatowich,

Transmembrane transfectors (carriers) are increasingly being viewed as helpful or even necessary to improve cellular delivery in connection with antisense tumor targeting and other applications requiring cell membrane transport of DNAs, RNAs, and other oligomers. We are investigating streptavidin as a convenient linker for biotinylated carriers and oligomers because it requires only simple mixing for preparation. The goal of this study was to evaluate antisense DNA-streptavidin-carrier nanoparticles for accumulation in cell culture and in xenograft-bearing mice. METHODS: The 3 carriers were cholesterol, a 10-mer Tat peptide, and a 10-mer polyarginine peptide. A 20-mer DNA targeting the mdr1 messenger RNA coding for Pgp expression was used as the phosphodiester (PO) DNA as well as the phosphorothioate (PS) DNA. In all cases, the (99m)Tc radiolabel was on the DNA. The 8 nanoparticles were first tested in mdr1(++) KB-G2 and TCO-1 cells and in mdr1(+/-) KB-31 cells in culture for evidence of improved accumulation and antisense targeting. Thereafter, the PS DNA-streptavidin-Tat, PO DNA-streptavidin-Tat, and PS DNA-streptavidin-cholesterol nanoparticles were administered intravenously to KB-G2 xenograft-bearing mice, and tissue distributions were measured. RESULTS: In culture, the PO nanoparticles showed increased accumulation compared with the corresponding nanoparticles without the carrier in all 3 cell types; in contrast, with the PS nanoparticles, any similar carrier-mediated increase may have been obscured by the much higher protein-binding affinity of PS DNA. As evidence of antisense targeting, the Tat and cholesterol PS nanoparticles showed statistically significant accumulation at 23 h in cells in the descending order TCO-1, KB-G2, and KB-31, although there were no significant differences among the PO nanoparticles. In xenograft-bearing mice, the tissue accumulation of both forms of the PS nanoparticles greatly exceeded that of the PO nanoparticles and, including in the tumor, were similar to that obtained previously for naked PS DNA. CONCLUSION: The presence of the streptavidin linker had no obvious detrimental effect on the functions of the carriers and antisense DNAs. The higher protein-binding affinity of the PS nanoparticles than the PO nanoparticles was still apparent both in vitro and in vivo, the pharmacokinetics of the PS nanoparticles were similar to that of naked PS DNA, and the carriers improved cellular accumulation, at least for the PO nanoparticles. These observations, taken together with the higher accumulation of both forms of the antisense PS nanoparticles in mdr1(++) KB-G2 and TCO-1 cells than in mdr1(+/-) KB-31 cells, suggest that further effort is justified to confirm that the antisense properties of the DNAs were not compromised by the presence of streptavidin.

Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker. Publishing Authors By Initials

K Nakamura,Y Wang,X Liu,A Kubo,DJ Hnatowich,K Nakamura,Y Wang,X Liu,A Kubo,DJ Hnatowich,

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Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of nuclear medicine : official publication

VOLUME: 48

Page Numbers: 1845-52

Journal Abbreviation: J. Nucl. Med.

ISSN: 0161-5505

DAY: 5

MONTH: Nov

YEAR: 2007

Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker. Information

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LANGUAGE: eng

NlmUniqueID: 217410

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Grant and Affiliation Information for Cell culture and xenograft-bearing animal studies of radiolabeled antisense DNA carrier nanoparticles with streptavidin as a linker.

AFFILIATION: Department of Radiology, Keio University School of Medicine, Tokyo, Japan. kumako@sc.itc.keio.ac.jp

Country: United States

AGENCY: United States NCI

GRANT: SR21 CA100092

ACRONYM: CA

MEDLINETA: J Nucl Med

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