Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery.

Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery. Research Abstract Details 

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Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery. Abstract Text:

X Liu,Y Wang,K Nakamura,A Kubo,D J Hnatowich,X Liu,Y Wang,K Nakamura,A Kubo,D J Hnatowich,X Liu,Y Wang,K Nakamura,A Kubo,D J Hnatowich,X Liu,Y Wang,K Nakamura,A Kubo,D J Hnatowich,

The three-component nanoparticle of this investigation consisted of an anti-type I regulatory subunit alpha of the cyclic AMP-dependent protein kinase A (RIalpha) antisense phosphorodiamidate morpholino (MORF) oligomer, a tat peptide and the anti-HER2 Herceptin antibody each biotinylated and each linked via streptavidin and tested in SUM190 (HER2+), SUM149 (HER2-) and SK-BR-3 (HER2+) cells in culture, using both radioactivity and fluorescent labels on the antisense and control sense MORF. Within the nanoparticle, the antibody provides specific binding to the target cells, the tat improves cellular delivery and the MORF provides the specific retention of the radioactivity in the target cell nucleus. The results show that within the nanoparticle, the Herceptin was still able to bind to its determinant; that the MORF escaped entrapment with its mRNA-binding ability preserved and that the tat maintained its carrier function. Fluorescence microscopy showed evidence of antisense MORF internalization, separation from Herceptin and migration to the nucleus. In conclusion, streptavidin appears to provide an easy means of mixing and matching components to improve the tumor-specific targeting, cell membrane transport, pharmacokinetics and other properties of antisense and other oligomers. Combining the three components of this investigation with streptavidin apparently did not interfere with the properties of each component in cell culture and significantly improved delivery.Cancer Gene Therapy (2008) 15, 126-132; doi:10.1038/sj.cgt.7701111; published online 14 December 2007.

Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery. Publishing Authors By Initials

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

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Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer gene therapy

VOLUME: 15

Page Numbers: 126-32

Journal Abbreviation: Cancer Gene Ther.

ISSN: 1476-5500

DAY: 14

MONTH: 12

YEAR: 2007

Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery. Information

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LANGUAGE: eng

NlmUniqueID: 9432230

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Grant and Affiliation Information for Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle designed for improved tumor delivery.

AFFILIATION: 1Department of Radiology, Division of Nuclear Medicine, University of Massachusetts Medical School, Worcester, MA, USA.

Country: England

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MEDLINETA: Cancer Gene Ther

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