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

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

Evaluating susceptibility of karst dolines (sinkholes) for collapse in Sango, Tennessee, USA

Dolines or sinkholes are earth depressions that develop in soluble rocks complexes such as limestone, dolomite, gypsum, anhydrite, and halite; dolines appear in a variety of shapes from nearly circular to complex structures with highly curved perimeters. The occurrence of dolines in the studied karst area is not random; they are the results of geomorphic, hydrologic and chemical processes that have caused partial subsidence, even total collapse of the land surface, when voids and caves are present in the bedrock and the regolith arch overbridging these voids is unstable. In the study area, the majority of collapses occur in the regolith (bedrock cover) that bridges voids in the bedrock. Because these collapsing dolines can damage property and cause even the loss of lives, there is a need to develop methods for evaluating karst hazards; such methods can be used by planners and practitioners for urban and economic development, especially in regions with a growing population. The purpose of this project is threefold: 1) to develop a karst feature database, 2) to investigate critical indicators associated with doline collapse, and 3) to design a doline susceptibility model for potential doline collapse based on external morphometric data. The study revealed the presence of short range spatial dependence in the distribution of the dolines’ morphometric parameters such as circularity, geographic orientation of the main doline axes and the length-to-width doline ratios; therefore, geostatistics can be used to spatially evaluate the susceptibility of the karst area for doline collapse using the probability of occurrence of these critical parameters. The partial susceptibility estimates were combined into final spatial probabilities enabling the identification of areas where undetected dolines may cause significant hazards

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

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