Auger radiation-induced, antisense-mediated cytotoxicity of tumor cells using a 3-component streptavidin-delivery nanoparticle with 111In
Authors
Liu, XinrongWang, Yi
Nakamura, Kayoko
Kawauchi, Sumi
Akalin, Ali
Cheng, Dengfeng
Chen, Ling
Rusckowski, Mary
Hnatowich, Donald J.
UMass Chan Affiliations
Department of PathologyDepartment of Radiology, Division of Nuclear Medicine
Document Type
Journal ArticlePublication Date
2009-04-01Keywords
AnimalsCell Line, Tumor
Cell Survival
DNA, Antisense
Drug Carriers
Female
Indium Radioisotopes
Mice
Mice, Nude
Nanoparticles
Neoplasms
Radiopharmaceuticals
Streptavidin
Treatment Outcome
antisense oligomer
delivery nanoparticle
radiotherapy
Auger electron–emitting radionuclide
streptavidin
Nanomedicine
Neoplasms
Radiochemistry
Radiology
Therapeutics
Metadata
Show full item recordAbstract
When antisense oligomers are intracellular, they migrate to and are retained in the nucleus of tumor cells and therefore may be used to carry Auger electron-emitting radionuclides such as (111)In for effective tumor radiotherapy. METHODS: Our nanoparticle consists of streptavidin that links 3 biotinylated components: the antiHer2 antibody trastuzumab (to improve pharmacokinetics), the tat peptide (to improve cell membrane transport), and the (111)In-labeled antiRIalpha messenger RNA antisense morpholino (MORF) oligomer. RESULTS: As evidence of unimpaired function, tumor cell and nuclear accumulations were orders of magnitude higher after incubation with (99m)Tc-MORF/tat/trastuzumab than after incubation with free (99m)Tc-MORF and significantly higher with the antisense than with the sense MORF. In mice, tumor and normal-tissue accumulations of the (99m)Tc-MORF/tat/trastuzumab nanoparticle were comparable to those of free (99m)Tc-trastuzumab, confirming the improved pharmacokinetics due to the trastuzumab component. Although kidneys, liver, and other normal tissues also accumulated the nanoparticle, immunohistochemical evaluation of tissue sections in mice receiving the Cy3-MORF/tat/trastuzumab nanoparticle showed evidence of nuclear accumulation only in tumor tissue. In a dose escalation study, as measured by the surviving fraction, the nanoparticle significantly increased the kill of SK-BR-3 breast cancer Her2+/RIalpha+ cells, compared with all controls. CONCLUSION: Significant radiation-induced antisense-mediated cytotoxicity of tumor cells in vitro was achieved using an Auger electron-emitting antisense MORF oligomer administered as a member of a 3-component streptavidin-delivery nanoparticle.Source
J Nucl Med. 2009 Apr;50(4):582-90. doi: 10.2967/jnumed.108.056366. Epub 2009 Mar 16.Link to article on publisher's site.DOI
10.2967/jnumed.108.056366Permanent Link to this Item
http://hdl.handle.net/20.500.14038/47994PubMed ID
19289423Notes
At the time of publication, Kayoko Nakamura was not yet associated with the University of Massachusetts Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.2967/jnumed.108.056366