Auger-mediated cytotoxicity of cancer cells in culture by an 125I-antisense oligomer delivered as a three-component streptavidin nanoparticle.
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.
Liu
Xinrong
X
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Nakamura
Kayoko
K
Wang
Yi
Y
Cheng
Dengfeng
D
Liang
Minmin
M
Xiao
Nan
N
Chen
Ling
L
Rusckowski
Mary
M
Hnatowich
Donald J
DJ
D000911:Antibodies, Monoclonal / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000494:pharmacology*; D009025:Morpholines / Q000378:metabolism; D060172:Morpholinos; D053758:Nanoparticles / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D019809:Streptavidin / Q000737:chemistry*; D000068878:Trastuzumab; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D007457:Iodine Radioisotopes; D009025:Morpholines; D060172:Morpholinos; D016376:Oligonucleotides, Antisense; D019809:Streptavidin; D000068878:Trastuzumab