Żuk Michał, Podgórski Rafał, Ruszczyńska Anna, Ciach Tomasz, Majkowska-Pilip Agnieszka, Bilewicz Aleksander, Krysiński Paweł
Faculty of Chemistry, University of Warsaw, Pasteura 1 Str., 02-093 Warsaw, Poland.
Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warynskiego 1 Str., 00-645 Warsaw, Poland.
Pharmaceutics. 2022 Aug 12;14(8):1680. doi: 10.3390/pharmaceutics14081680.
Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (FeO) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody-trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.
氧化铁纳米颗粒常用于许多医学应用中，因为它们易于修饰、具有高的表面体积比，并且具有生物相容性和可生物降解性。本研究旨在合成用于多模态HER2阳性癌症治疗的纳米颗粒，涉及放射性核素治疗和磁热疗。磁性核心（FeO）涂有一层金-198，形成所谓的核壳纳米颗粒。然后用双功能聚乙二醇连接体和单克隆抗体对其进行进一步修饰，以实现靶向治疗。单克隆抗体曲妥珠单抗用于靶向特定的乳腺和乳头HER2阳性癌细胞。通过透射电子显微镜测量的纳米颗粒小至9纳米。通过两种独立的方法证实了曲妥珠单抗的生物偶联：热重分析和碘-131标记。合成的纳米颗粒表明，它们在交变磁场中是良好的热介质，并且对SKOV-3（HER2阳性）癌细胞系表现出很强的特异性结合和内化能力。放射性纳米颗粒在有无磁热疗的情况下也表现出球体降解能力，在后一种情况下影响更大。设计的放射生物偶联物显示出巨大的前景，在磁热疗和放射性核素联合治疗的体内研究中具有巨大潜力。
