Żelechowska-Matysiak Kinga, Wawrowicz Kamil, Wierzbicki Mateusz, Budlewski Tadeusz, Bilewicz Aleksander, Majkowska-Pilip Agnieszka
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 St., Warsaw 03-195, Poland.
Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Ciszewskiego 8 St., Warsaw 02-786, Poland.
Mol Pharm. 2025 Jul 7;22(7):4019-4031. doi: 10.1021/acs.molpharmaceut.5c00288. Epub 2025 May 29.
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 (AuNPs) and trastuzumab emtansine (T-DM1; Kadcyla) for targeted therapy of cancers with established HER2 receptor overexpression. By utilizing AuNPs-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 AuNPs-T-DM1 for HER2 receptors and its effective internalization. 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 AuNPs-T-DM1 at 20 MBq/mL and T-DM1 concentration of 0.031 μg/mL disintegrated 3D spheroid structures within seven days. The synthesized AuNP-T-DM1 radiobioconjugate has potential applications in nuclear medicine for treating breast or ovarian cancers with HER2 receptor overexpression.
一种现代癌症治疗概念是使用抗体药物偶联物(ADC)。这些疗法已显示出有前景的结果,尤其是与其他癌症治疗技术联合使用时。在本研究中,我们提出同时使用β辐射(金纳米颗粒)和曲妥珠单抗恩杂鲁胺(T-DM1;赫赛莱)对已确定HER2受体过表达的癌症进行靶向治疗。通过利用金纳米颗粒-T-DM1,我们旨在降低所需的T-DM1浓度,鉴于恩杂鲁胺相关的副作用,这是有利的。在我们的研究中,我们证明了偶联的金纳米颗粒-T-DM1对HER2受体的亲和力及其有效的内化作用。研究表明,在10 MBq/mL或20 MBq/mL的辐射剂量以及0.015至0.124 μg/mL的低浓度赫赛莱下存在协同治疗效果。以20 MBq/mL的金纳米颗粒-T-DM1和0.031 μg/mL的T-DM1浓度进行治疗,在七天内瓦解了三维球体结构。合成的金纳米颗粒-T-DM1放射生物偶联物在核医学中具有治疗HER2受体过表达的乳腺癌或卵巢癌的潜在应用。