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Successful radiotherapy of tumor cells using a three-component delivery nanoparticle and 111In

¹ Radiology, University of Massachusetts Medical School, Worcester, Massachusetts; ² Radiology, Keio University School of Medicine, Tokyo, Japan

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Objectives: Antisense (AS) oligomers migrate to and are retained in the nucleus of tumor cells and could provide effective radiotherapy if labeled with Auger emitters. Radiotherapy of a 3-component delivery streptavidin nanoparticle consisting of biotinylated Herceptin antiHER2 antibody, tat peptide transfector and 111In-antiRI mRNA AS MORF was evaluated in HER2+/ RI+ SK-BR-2 cells.

Methods: Cell viability was minimally inhibited by the unlabeled AS nanoparticle at 50 nM and no cytotoxicity was observed for both AS and sense (S) naked MORFs, both MORF 1-component, both MORF/tat 2-component, and both MORF/tat/Herceptin 3-component nanoparticles and streptavidin alone, all unlabeled. Therefore 50 nM was selected to ensure that radiotherapy would be specific to 111In carried to the nucleus.

Results: An upper limit of 30 uCi/well was set when no nonspecific cytotoxicity to the 111In-AS nanoparticle was observed at this dose or less. The radiotherapy trial used as endpoints the colony surviving fraction (SF) between cells incubated with the radiolabeled nanoparticles and incubated with PBS or unlabeled nanoparticles. The SF of cells incubated with 111In-AS but not the S nanoparticle decreased with increasing dose and was significantly lower in cells treated at 30 uCi/well compared to S and compared to free 111In.

Conclusions: The 3-component AS nanoparticle provided significantly higher tumor cell, nuclear accumulations and significantly lower SF compared to controls. These results confirm that radiotherapy is effective when 111In is added on an antisense MORF oliogomer and as a member of a 3-component streptavidin delivery nanoparticle.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Liu, X. Articles by Hnatowich, D. PubMed Articles by Liu, X. Articles by Hnatowich, D.