Radiobioconjugate of Kadcyla with Radioactive Gold Nanoparticles for Targeted Therapy of HER2-Overexpressing Cancers

One modern concept for cancer treatment is the use of antibody-drug conjugate (ADC). These therapies have shown promising results, especially in combination with other cancer treatment techniques. In this study, we propose the simultaneous use of β^- radiation (¹⁹⁸AuNPs) and trastuzumab emtansine (T-DM1; Kadcyla) for targeted therapy of cancers with established HER2 receptor overexpression. By utilizing ¹⁹⁸AuNPs-T-DM1, we aimed to reduce the required concentrations of T-DM1, which is advantageous given the associated emtansine-related side effects. In our study, we demonstrated the affinity of conjugated ¹⁹⁸AuNPs-T-DM1 for HER2 receptors and its effective internalization. <i>In vitro</i> studies indicate a synergistic therapeutic effect at doses of 10 MBq/mL or 20 MBq/mL of radiation and low concentrations of Kadcyla ranging from 0.015 to 0.124 μg/mL. Treatment with ¹⁹⁸AuNPs-T-DM1 at 20 MBq/mL and T-DM1 concentration of 0.031 μg/mL disintegrated 3D spheroid structures within seven days. The synthesized ¹⁹⁸AuNP-T-DM1 radiobioconjugate has potential applications in nuclear medicine for treating breast or ovarian cancers with HER2 receptor overexpression.