Evidence map›Paper›PMID 39281449›Full record

ArticleHeliyon2024

Nano-scale characterization of iron-carbohydrate complexes by cryogenic scanning transmission electron microscopy: Building the bridge to biorelevant characterization.

Reinaldo Digigow, Michael Burgert, Marco Luechinger, Alla Sologubenko, Andrzej J Rzepiela, Stephan Handschin, Amy E Barton Alston, Beat Flühmann, Erik Philipp

Abstract read
In one paragraph

Article in Heliyon, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Reinaldo DigigowCSL Vifor, Flughofstrasse 61, CH-8152, Glattbrugg, Switzerland.
Michael BurgertCSL Vifor, Flughofstrasse 61, CH-8152, Glattbrugg, Switzerland.
Marco LuechingerCSL Vifor, Flughofstrasse 61, CH-8152, Glattbrugg, Switzerland.
Alla SologubenkoScientific Center for Optical and Electron Microscopy, ScopeM, ETH Zürich, 8093, Zürich, Switzerland.
Andrzej J RzepielaScientific Center for Optical and Electron Microscopy, ScopeM, ETH Zürich, 8093, Zürich, Switzerland.
Stephan HandschinScientific Center for Optical and Electron Microscopy, ScopeM, ETH Zürich, 8093, Zürich, Switzerland.
Amy E Barton AlstonCSL Vifor, Flughofstrasse 61, CH-8152, Glattbrugg, Switzerland.
Beat FlühmannCSL Vifor, Flughofstrasse 61, CH-8152, Glattbrugg, Switzerland.
Erik PhilippCSL Vifor, Flughofstrasse 61, CH-8152, Glattbrugg, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Iron deficiency and iron deficiency anemia pose significant health challenges worldwide. Iron carbohydrate nanoparticles administered intravenously are a mainstay of treatment to deliver elemental iron safely and effectively. However, despite decades of clinical use, a complete understanding of their physical structure and the significance for their behavior, particularly at the nano-bio interface, is still lacking, underscoring the need to employ more sophisticated characterization methods. Our study used cryogenic Scanning Transmission Electron Microscopy (cryo-STEM) to examine iron carbohydrate nanoparticle morphology. This method builds upon previous research, where direct visualization of the iron cores in these complexes was achieved using cryogenic Transmission Electron Microscopy (cryo-TEM). Our study confirms that the average size of the iron cores within these nanoparticles is approximately 2 nm across all iron-based products studied. Furthermore, our investigation revealed the existence of discernible cluster-like morphologies, not only for ferumoxytol, as previously reported, but also within all the examined iron-carbohydrate products. The application of cryo-STEM for the analyses of product morphologies provides high-contrast and high-resolution images of the nanoparticles, and facilitates the characterization at liquid nitrogen temperature, thereby preserving the structural integrity of these complex samples. The findings from this study offer valuable insights into the physical structure of iron-carbohydrate nanoparticles, a crucial step towards unraveling the intricate relationship between the structure and function of this widely used drug class in treating iron deficiency. Additionally, we developed and utilized the self-supervised machine learning workflow for the image analysis of iron-carbohydrate complexes, which might be further expanded into a useful characterization tool for comparability studies.

Indexed as

Cryo-scanning transmission electron microscopy (cryo-STEM)Cryo-transmission electron microscopy (cryo-TEM)Iron-carbohydrate complexesIron deficiency anemiaNanomedicinesNanoparticles (NPs)Non-biological complex drugs (NBCDs)Physicochemical characterization of nanomedicines

Identifiers

PMID39281449
PMCPMC11401109

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.