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组织中金属氧化物纳米颗粒的多尺度分析:对生物分布和生物转化的见解

Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation.

作者信息

Matter Martin T, Li Jian-Hao, Lese Ioana, Schreiner Claudia, Bernard Laetitia, Scholder Olivier, Hubeli Jasmin, Keevend Kerda, Tsolaki Elena, Bertero Enrico, Bertazzo Sergio, Zboray Robert, Olariu Radu, Constantinescu Mihai A, Figi Renato, Herrmann Inge K

机构信息

Particles-Biology Interactions, Department of Materials Meet Life Swiss Federal Laboratories for Materials Science and Technology (Empa) Lerchenfeldstrasse 5 St. Gallen 9014 Switzerland.

Nanoparticle Systems Engineering Laboratory Institute of Process Engineering Department of Mechanical and Process Engineering ETH Zurich Sonneggstrasse 3 Zurich 8092 Switzerland.

出版信息

Adv Sci (Weinh). 2020 Jun 18;7(15):2000912. doi: 10.1002/advs.202000912. eCollection 2020 Aug.

DOI:10.1002/advs.202000912
PMID:32775166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7404155/
Abstract

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X-ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle-based systems.

摘要

金属氧化物纳米颗粒因其独特的物理化学特性,已成为极具潜力的生物医学传感器和致动器。尽管取得了令人瞩目的成就,但目前对纳米颗粒与周围组织之间分子相互作用的了解有限,这仍然是纳米药物合理开发的主要障碍,这一点从它们较低的临床批准率中可见一斑。这项工作以由结晶氧化铈和可生物降解陶瓷生物玻璃组成的复合金属氧化物纳米颗粒杂化物为例,报道了组织中无机纳米颗粒的纳米级表征。一种基于半定量X射线荧光和电感耦合等离子体质谱的经过验证的分析方法,用于评估静脉内和局部应用后纳米颗粒的生物分布。然后,基于显微镜和光谱技术相结合的相关多尺度分析级联表明,局部应用的杂化纳米颗粒保留在初始部位,并优先被巨噬细胞摄取,在其表面形成磷灰石,并导致其周围脂质积累增加。综上所述,这项工作展示了如何利用现代分析技术,以前所未有的方式深入了解复杂无机纳米颗粒的生物分布和生物转化。这种纳米级表征对于合理设计安全有效的基于纳米颗粒的系统至关重要。

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