Document Detail


Auger-mediated cytotoxicity of cancer cells in culture by an 125I-antisense oligomer delivered as a three-component streptavidin nanoparticle.
MedLine Citation:
PMID:  20738069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We reported recently that a three-component nanoparticle, consisting of a targeting antibody, a transfecting peptide and an 111In-antiRIalpha MORF antisense oligomer, provided Auger electron-mediated, antisense-mediated, cytotoxicity of cells in culture. We have now measured the cytotoxicity of the nanoparticle in culture with the 111In replaced by 125I, another attractive Auger electron emitter. The nanoparticle consisted of streptavidin linking the 125I labeled antiRIalpha mRNA antisense MORF oligomer, the tat transfecting peptide and the anti-Her2 Trastuzumab antibody. Cytotoxicity was evaluated by a clonogenic survival assay in BT-474 (Her2+) human breast cancer cells. In a dose escalation study, as measured by the surviving fraction, the cytotoxicity of tumor cells to the 125I-labeled antisense nanoparticle was significantly higher than that for the identical sense control. When compared with our previous study with 111In as label, a similar level of cytotoxicity was achieved but the observed minimal therapeutic dose for the 125I-labeled nanoparticle in BT-474 cells was lower than that for 111In-labeled nanoparticle in SK-BR-3 cells. Thus, a radiolabeled antisense MORF oligomer delivered into cells by a three-component nanoparticle is an effective vehicle for Auger radiotherapy when radiolabeled with 111In or 125I.
Authors:
Xinrong Liu; Kayoko Nakamura; Yi Wang; Dengfeng Cheng; Minmin Liang; Nan Xiao; Ling Chen; Mary Rusckowski; Donald J Hnatowich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of biomedical nanotechnology     Volume:  6     ISSN:  1550-7033     ISO Abbreviation:  J Biomed Nanotechnol     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-08-26     Completed Date:  2010-09-16     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  101230869     Medline TA:  J Biomed Nanotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-7     Citation Subset:  IM    
Affiliation:
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / metabolism
Antibodies, Monoclonal, Humanized
Antineoplastic Agents / chemistry,  pharmacology*
Breast Neoplasms
Cell Line, Tumor
Cell Survival / drug effects
Chromatography, Gel
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics,  metabolism
Dose-Response Relationship, Radiation
Drug Delivery Systems / methods*
Female
Humans
Iodine Radioisotopes / chemistry,  pharmacology*
Morpholines / metabolism
Morpholinos
Nanoparticles / chemistry*
Oligonucleotides, Antisense / chemistry,  pharmacology*
Streptavidin / chemistry*
Tumor Stem Cell Assay
Grant Support
ID/Acronym/Agency:
R21CA129591/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents; 0/Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0/Iodine Radioisotopes; 0/Morpholines; 0/Morpholinos; 0/Oligonucleotides, Antisense; 9013-20-1/Streptavidin; P188ANX8CK/trastuzumab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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