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

• Published in: Advanced science 2020-08, Vol.7 (15), p.2000912-n/a
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: analytical imaging; biological fate; multiscale; nanosafety; spectral unmixing
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202000912

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. The development of novel nanotherapeutics requires an in‐depth understanding of their molecular interplay with biology. This multidisciplinary work elucidates the biodistribution, biotransformation, and local biological impact of complex inorganic nanoparticles using a correlative cascade of advanced elemental analysis, label‐free microscopy, and spectroscopy techniques. This work illustrates the potential of advanced analytical techniques to deepen the understanding of nanotherapeutics.