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关于纳米L型沸石在生物医学应用中的多功能性:锆-89放射性标记及体内正电子发射断层扫描研究

On the Versatility of Nanozeolite Linde Type L for Biomedical Applications: Zirconium-89 Radiolabeling and In Vivo Positron Emission Tomography Study.

作者信息

Lacerda Sara, Zhang Wuyuan, T M de Rosales Rafael, Da Silva Isidro, Sobilo Julien, Lerondel Stéphanie, Tóth Éva, Djanashvili Kristina

机构信息

Centre de Biophysique Moléculaire, CNRS UPR4301, Rue Charles Sadron, Orléans 45071 Cedex 2, France.

Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, Delft 2629 HZ, The Netherlands.

出版信息

ACS Appl Mater Interfaces. 2022 Jul 13;14(29):32788-98. doi: 10.1021/acsami.2c03841.

Abstract

Porous materials, such as zeolites, have great potential for biomedical applications, thanks to their ability to accommodate positively charged metal-ions and their facile surface functionalization. Although the latter aspect is important to endow the nanoparticles with chemical/colloidal stability and desired biological properties, the possibility for simple ion-exchange enables easy switching between imaging modalities and/or combination with therapy, depending on the envisioned application. In this study, the nanozeolite Linde type L (LTL) with already confirmed magnetic resonance imaging properties, generated by the paramagnetic gadolinium (Gd) in the inner cavities, was successfully radiolabeled with a positron emission tomography (PET)-tracer zirconium-89 (Zr). Thereby, exploiting Zr-chloride resulted in a slightly higher radiolabeling in the inner cavities compared to the commonly used Zr-oxalate, which apparently remained on the surface of LTL. Intravenous injection of PEGylated Zr/Gd-LTL in healthy mice allowed for PET-computed tomography evaluation, revealing initial lung uptake followed by gradual migration of LTL to the liver and spleen. Ex vivo biodistribution confirmed the in vivo stability and integrity of the proposed multimodal probe by demonstrating the original metal/Si ratio being preserved in the organs. These findings reveal beneficial biological behavior of the nanozeolite LTL and hence open the door for follow-up theranostic studies by exploiting the immense variety of metal-based radioisotopes.

摘要

诸如沸石之类的多孔材料在生物医学应用方面具有巨大潜力,这得益于它们容纳带正电金属离子的能力以及易于进行表面功能化。尽管后一个方面对于赋予纳米颗粒化学/胶体稳定性和所需生物学特性很重要,但简单的离子交换可能性能够根据预期应用在成像模式之间轻松切换和/或与治疗相结合。在本研究中,由内腔中的顺磁性钆(Gd)产生的、已证实具有磁共振成像特性的纳米Linde型L沸石(LTL)成功地用正电子发射断层扫描(PET)示踪剂锆-89(Zr)进行了放射性标记。由此,与通常留在LTL表面的草酸锆相比,利用氯化锆在内腔中产生的放射性标记略高。在健康小鼠中静脉注射聚乙二醇化的Zr/Gd-LTL后进行PET计算机断层扫描评估,结果显示最初肺部摄取,随后LTL逐渐迁移至肝脏和脾脏。体外生物分布通过证明器官中原始金属/硅比例得以保留,证实了所提出的多模态探针在体内的稳定性和完整性。这些发现揭示了纳米LTL有益的生物学行为,因此为利用种类繁多的金属基放射性同位素开展后续的治疗诊断研究打开了大门。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a6e/9335405/eccef37fdee0/am2c03841_0002.jpg

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