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用于多模态癌症治疗的基于杂交放射生物共轭超顺磁性氧化铁的纳米颗粒

Hybrid Radiobioconjugated Superparamagnetic Iron Oxide-Based Nanoparticles for Multimodal Cancer Therapy.

作者信息

Żuk Michał, Gawęda Weronika, Majkowska-Pilip Agnieszka, Osial Magdalena, Wolski Marcin, Bilewicz Aleksander, Krysiński Paweł

机构信息

Faculty of Chemistry, University of Warsaw, Pasteura 1 Str., 02-093 Warsaw, Poland.

Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, Poland.

出版信息

Pharmaceutics. 2021 Nov 2;13(11):1843. doi: 10.3390/pharmaceutics13111843.

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biomedical applications for their outstanding properties such as facile functionalization and doping with different metals, high surface-to-volume ratio, superparamagnetism, and biocompatibility. This study was designed to synthesize and investigate multifunctional nanoparticle conjugate to act as both a magnetic agent, anticancer immunological drug, and radiopharmaceutic for anticancer therapy. The carrier, Ho doped iron oxide, was coated with an Au layer, creating core-shell nanoparticles ([Ho] FeO@Au. These nanoparticles were subsequently modified with monoclonal antibody trastuzumab (Tmab) to target HER2+ receptors. We describe the radiobioconjugate preparation involving doping of a radioactive agent and attachment of the organic linker and drug to the SPIONs' surface. The size of the SPIONs coated with an Au shell measured by transmission electron microscopy was about 15 nm. The bioconjugation of trastuzumab onto SPIONs was confirmed by thermogravimetric analysis, and the amount of two molecules per one nanoparticle was estimated with the use of radioiodinated [I]Tmab. The synthesized bioconjugates showed that they are efficient heat mediators and also exhibit a cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptors. Prepared radiobioconjugates reveal the high potential for in vivo application of the proposed multimodal hybrid system, combined with magnetic hyperthermia and immunotherapy against cancer tissues.

摘要

超顺磁性氧化铁纳米颗粒(SPIONs)因其具有诸如易于功能化和用不同金属掺杂、高比表面积、超顺磁性和生物相容性等优异特性,而被广泛应用于生物医学领域。本研究旨在合成并研究多功能纳米颗粒缀合物,使其兼具磁性剂、抗癌免疫药物和用于抗癌治疗的放射性药物的作用。载体钬掺杂的氧化铁被金层包覆,形成核壳纳米颗粒([Ho]FeO@Au)。随后,这些纳米颗粒用单克隆抗体曲妥珠单抗(Tmab)进行修饰,以靶向HER2+受体。我们描述了放射性生物缀合物的制备过程,包括掺杂放射性试剂以及将有机连接体和药物连接到SPIONs表面。通过透射电子显微镜测量,包覆金壳的SPIONs尺寸约为15nm。通过热重分析证实了曲妥珠单抗与SPIONs的生物缀合,并使用放射性碘化[I]Tmab估计每个纳米颗粒上两种分子的数量。合成的生物缀合物表明它们是有效的热介质,并且对表达HER2受体的SKOV-3卵巢癌细胞也表现出细胞毒性作用。制备的放射性生物缀合物显示出所提出的多模态混合系统在体内应用的巨大潜力,可与磁热疗和针对癌组织的免疫疗法相结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f39b/8619896/eca50f10193a/pharmaceutics-13-01843-g001.jpg

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