Cytoplasmic and Nuclear Accumulation of Antisense Oligomers Incubated as Streptavidin Delivery Nanoparticles

Author(s): Xinrong Liu, Yi Wang, Kayoko Nakamura, Guozheng Liu, Ling Chen, Shuping Dou, Mary Rusckowski, Donald J. Hnatowich

Journal Name: Current Radiopharmaceuticals

Volume 2 , Issue 2 , 2009

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Abstract:

The cytoplasmic accumulation and nuclear targeting of antisense oligomers were evaluated in cell culture following incubation with the cell penetrating peptide tat or polyargenine as a two-component delivery nanoparticle using streptavidin as linker. The fluorescent labeled uniform phosphodiester (PO), phosphorothioate (PS) and MORF oligomers were antisense to the mdr1 mRNA and were studied in KB-G2 (Pgp++) and KB-31 (Pgp+/-) cells. Fluorescence microscopy showed much higher cellular accumulation using the antisense compared to the sense PS/tat nanoparticle. The distribution in cells receiving either the PS or MORF, but not the PO, antisense oligomers in all of their forms showed definite migration to the nucleus. Incubations in KB-G2 cells of all three antisense oligomers with streptavidin as the onecomponent or including tat as the two-component nanoparticles led to increases in Rhodamine 123 accumulation by 200∼250% compared to free oligomers, almost certainly due to antisense interference with Pgp function. Thus presence of the streptavidin linker had no obvious detrimental influence on the functions of the carriers or the antisense oligomers. Since nuclear migration appears to be a characteristic property of oligomers, delivery via the nanoparticle may be a useful method of increasing the accumulation into the nucleus of antisense oligomers radiolabeled for Auger emittingbased radiotherapy.

Keywords: Nanoparticle, streptavidin, mdr1, antisense oligomer, nuclear migration

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Article Details

VOLUME: 2
ISSUE: 2
Year: 2009
Page: [112 - 117]
Pages: 6
DOI: 10.2174/1874471010902020112
Price: $65

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