Au@Pd Core-Shell Nanoparticles Conjugated to Panitumumab for the Combined β-Auger Electron Therapy of Triple-Negative Breast Cancer.

Apart from HER2-positive, triple-negative breast cancer (TNBC) is the second most highly invasive type of breast cancer. Although TNBC does not overexpress HER2 receptors, it has been observed that EGFR protein expression is present in this specific type of tumor, making it an attractive target for immune and radiopharmaceutical treatments. In our current study, we used Pd (T = 13.7 h) in the form of a Pd/Ag in vivo generator as a source of β particles and Auger electrons in targeted radionuclide therapy for TNBC. Pd, obtained through neutron irradiation of the Pd target, was deposited onto 15 nm gold nanoparticles to form Au@Pd core-shell nanoparticles, which were then conjugated to the panitumumab antibody. Au@Pd-PEG-panitumumab nanoparticles were bound, internalized, and partially routed to the nucleus in MDA-MB-231 human breast cancer cells overexpressing EGFR receptors. The Au@Pd-panitumumab radioconjugate significantly reduced the metabolic activity of MDA-MB-231 cells in a dose-dependent manner. In conclusion, we have found that Au@Pd-PEG-panitumumab nanoparticles show potential as a therapeutic agent for combined β-Auger electron targeted radionuclide therapy of TNBC. The simultaneous emission of β, conversion, and Auger electrons from the Pd/Ag generator, similar to Tb conjugates, significantly enhances the therapeutic effect. The partial localization of these nanoparticles into the cell nucleus, provided by the panitumumab vector, ensures effective therapy with Auger electrons. This is particularly important for the treatment of drug-resistant TNBC cells.