Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix

Stachnik, Karolina; Warmer, Martin; Mohácsi, István; Hennicke, V.; Fischer, P.; Meyer, Jan; Spitzbart, Tobias; Barthelmeß, Miriam; Eich, Jacqueline; Dávid, Christian; Feldmann, Claus; Busse, Björn; Jähn, Katharina; Schaible, Ulrich E.; Meents, A.

doi:10.1038/s41598-020-58318-7

Cited by 7 publications

(5 citation statements)

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“…For ptychographic tomography, this will mean continuous scanning, short exposure times, high frame rates and a high demand for computing. Most likely, experiments will also want to make use of other contrast mechanisms such as X-ray fluorescence, X-ray beam-induced voltage/current and the signal under Bragg condition simultaneously with ptychographic measurements (Kahnt et al, 2018;Stachnik et al, 2020). In those cases, an online reconstruction of all recorded scans can probably not be offered.…”

Section: Figurementioning

confidence: 99%

First ptychographic X-ray computed tomography experiment on the NanoMAX beamline

et al. 2020

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Ptychographic X-ray computed tomography is a quantitative three-dimensional imaging technique offered to users of multiple synchrotron radiation sources. Its dependence on the coherent fraction of the available X-ray beam makes it perfectly suited to diffraction-limited storage rings. Although MAX IV is the first, and so far only, operating fourth-generation synchrotron light source, none of its experimental stations is currently set up to offer this technique to its users. The first ptychographic X-ray computed tomography experiment has therefore been performed on the NanoMAX beamline. From the results, information was gained about the current limitations of the experimental setup and where attention should be focused for improvement. The extracted parameters in terms of scanning speed, size of the imaged volume and achieved resolutions should provide a baseline for future users designing nano-tomography experiments on the NanoMAX beamline.

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Section: Figurementioning

confidence: 99%

First ptychographic X-ray computed tomography experiment on the NanoMAX beamline

et al. 2020

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“…Additionally, local bone mineral content seems to be controlled by osteocytes, which has been supported by us and others using high-resolution synchrotron determining differential mineralization around the osteocyte lacunae. (36,37) The lower global mineralization degree in combination with the observed osteocyte activity-induced changes may potentially contribute to increased bone fragility in hyperthyroid patients.…”

Section: Discussionmentioning

confidence: 99%

Reduced Bone Mass and Increased Osteocyte Tartrate-Resistant Acid Phosphatase (TRAP) Activity, But Not Low Mineralized Matrix Around Osteocyte Lacunae, Are Restored After Recovery From Exogenous Hyperthyroidism in Male Mice

Wölfel

Lademann

Hemmatian

et al. 2020

Journal of Bone and Mineral Research

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Hyperthyroidism causes secondary osteoporosis through favoring bone resorption over bone formation, leading to bone loss with elevated bone fragility. Osteocytes that reside within lacunae inside the mineralized bone matrix orchestrate the process of bone remodeling and can themselves actively resorb bone upon certain stimuli. Nevertheless, the interaction between thyroid hormones and osteocytes and the impact of hyperthyroidism on osteocyte cell function are still unknown. In a preliminary study, we analyzed bones from male C57BL/6 mice with drug‐induced hyperthyroidism, which led to mild osteocytic osteolysis with 1.14‐fold larger osteocyte lacunae and by 108.33% higher tartrate‐resistant acid phosphatase (TRAP) activity in osteocytes of hyperthyroid mice compared to euthyroid mice. To test whether hyperthyroidism‐induced bone changes are reversible, we rendered male mice hyperthyroid by adding levothyroxine into their drinking water for 4 weeks, followed by a weaning period of 4 weeks with access to normal drinking water. Hyperthyroid mice displayed cortical and trabecular bone loss due to high bone turnover, which recovered with weaning. Although canalicular number and osteocyte lacunar area were similar in euthyroid, hyperthyroid and weaned mice, the number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling (TUNEL)‐positive osteocytes was 100% lower in the weaning group compared to euthyroid mice and the osteocytic TRAP activity was eightfold higher in hyperthyroid animals. The latter, along with a 3.75% lower average mineralization around the osteocyte lacunae in trabecular bone, suggests osteocytic osteolysis activity that, however, did not result in significantly enlarged osteocyte lacunae. In conclusion, we show a recovery of bone microarchitecture and turnover after reversal of hyperthyroidism to a euthyroid state. In contrast, osteocytic osteolysis was initiated in hyperthyroidism, but its effects were not reversed after 4 weeks of weaning. Due to the vast number of osteocytes in bone, we speculate that even minor individual cell functions might contribute to altered bone quality and mineral homeostasis in the setting of hyperthyroidism‐induced bone disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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“…An iterative algorithm is then used to reconstruct a 2D image with an amplitude and phase contrast. By coupling XFR with ptychography, Stachnik et al [ 166 ] have mapped quantitatively the distribution of antibiotic loaded‐iron oxide NCs within macrophages, simultaneously with the identification of the different sub‐cellular structures, with a spatial resolution below 100 nm.…”

Section: Other Approachesmentioning

confidence: 99%

Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

Chaupard

Frutos

Gref

2021

Part & Part Syst Charact

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payload's pharmacokinetics and contributed to achieve the desired pharmacological response at the target. They are now widely exploited for therapeutic purposes, including the treatment of severe diseases such as cancer and infections. [1] A plethora of natural and synthetic materials have been engineered at a nanoscopic level and explored for drug delivery (Figure 1). Liposomes, the first nanotechnology-based drug delivery system, were discovered early in the 1960s. [2] The first Food and Drug Administration (FDA)-approved nanotechnology was the liposomal Doxil formulation designed for the treatment of Kaposi's sarcoma and since then, more than twenty liposomal and lipid-based formulations have been approved by regular authorities. [3] Many other types of drug nanocarriers have been developed, including polymeric, hybrid or metal nanoparticles (NPs), nanogels, dendrimers, quantum dots, carbon nanotubes (CNTs), and micelles (Figure 1). Several nanotechnologies containing an active molecule or a drug combination, such as Onpattro and Vyxeos, were FDA-approved in recent years, demonstrating the potential of nanomedicine and the growing interest in this field. [4,5] Moreover, the FDA-approved NP-based vaccines represent a giant step in the fight against the COVID-19 pandemic. [6] Nowadays, a large variety of materials is used to prepare drug nanocarriers: i) organic compounds (lipids, synthetic or natural polymers, biomolecules); ii) inorganic materials (silica, carbon networks, metals, or metal oxides) and iii) hybrid organic-inorganic networks combining the properties of both their organic and inorganic counterparts. Generally, drug nanocarriers have a core-shell structure: i) the cores incorporate the drugs and release them in a controlled manner and ii) the shells govern the interactions with the living media (control protein adsorption, avoid recognition by the immune system, allow targeting diseased tissues and organs, confer bio-adhesion properties). Organic compounds remain the most employed materials for drug incorporation and for engineering multifunctional shells. Additionally, the presence of metals in drug nanocarriers' composition offers new functionalities, such as antibacterial or antifungal properties, [7] radioenhancement [8] or imaging abilities for personalized therapies. [9] More recently, nanoscale hybrid metal-organic frameworks (MOFs) emerged as versatile Drug nanocarriers (NCs) with sizes usually below 200 nm are gaining increasing interest in the treatment of severe diseases such as cancer and infections. Characterization methods to investigate the morphology and physicochemical properties of multifunctional NCs are key in their optimization and in the study of their in vitro and in vivo fate. Whereas a variety of methods has been developed to characterize "bulk" NCs in suspension, the scope of this review is to describe the different approaches for the NC characterization on an individual basis, for which fewer techniques are available. The accent is put on methods devoid of labelling, whi...

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Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix

Cited by 7 publications

References 58 publications

First ptychographic X-ray computed tomography experiment on the NanoMAX beamline

First ptychographic X-ray computed tomography experiment on the NanoMAX beamline

Reduced Bone Mass and Increased Osteocyte Tartrate-Resistant Acid Phosphatase (TRAP) Activity, But Not Low Mineralized Matrix Around Osteocyte Lacunae, Are Restored After Recovery From Exogenous Hyperthyroidism in Male Mice

Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

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