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-antiRIα MORF antisense oligomer, provided Auger electronmediated, 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 antiRIα 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.