Evidence map›Paper›PMID 40887945›Full record

ArticleMicroscopy research and technique2026

Combining Correlative Cryogenic Fluorescence and Electron Microscopy and Correlative Cryogenic Super-Resolution Fluorescence and X-Ray Tomography-Novel Complementary 3D Cryo-Microscopy Across Scales to Reveal Nanoparticle Internalization Into Cancer Cells.

Pavitra Sokke Rudraiah, Louisa Herbsleb, Michaela Salakova, Henriette Gröger, Anna Maria Steyer, Frauke Alves, Claus Feldmann, Andreas Walter

Abstract read
In one paragraph

Article in Microscopy research and technique, 2026. 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. Article
  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

8 authors.

Pavitra Sokke RudraiahCenter for Optical Technologies, Aalen University, Aalen, Germany.ORCID https://orcid.org/0009-0008-9477-2410
Louisa HerbslebCenter for Optical Technologies, Aalen University, Aalen, Germany.
Michaela SalakovaCenter for Optical Technologies, Aalen University, Aalen, Germany.
Henriette GrögerInstitute of Inorganic Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Anna Maria SteyerEMBL Imaging Centre, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID https://orcid.org/0000-0002-4814-7517
Frauke AlvesTranslational Molecular Imaging, Max-Planck-Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID https://orcid.org/0000-0002-6258-5409
Claus FeldmannInstitute of Inorganic Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.ORCID https://orcid.org/0000-0003-2426-9461
Andreas WalterCenter for Optical Technologies, Aalen University, Aalen, Germany.ORCID https://orcid.org/0000-0002-4096-1944

Funding

Diamond Light Source
6 · The paper itself

Abstract

Understanding the intracellular fate of nanoparticles (NPs) is essential for advancing nanomedicine, particularly in targeted drug delivery for cancer therapy. Here, we present a complementary cryogenic microscopy workflow across scales to investigate the uptake and subcellular localization of zirconyl-containing inorganic-organic hybrid nanoparticles (IOH-NPs) in murine breast cancer cells. Our approach integrates cryogenic fluorescence microscopy (cryo-FM), cryo-focused ion beam scanning electron microscopy (cryo-FIBSEM), and cryo-soft X-ray tomography (cryo-SXT), enabling molecular specificity, high-resolution imaging, and volumetric ultrastructural analysis in near-native cellular states. We demonstrate that the cryogenic workflow provides enough contrast and resolution across all modalities for quantifying the IOH-NP uptake: NPs are internalized within 2 h of incubation and progressively accumulate in endolysosomes over time, as confirmed by fluorescence labeling and SXT. Quantitative analysis reveals a marked increase in endolysosomal accumulation of IOH-NPs from 2 to 24 h. Our findings help to establish multimodal cryogenic microscopy as a powerful tool for nanoscale imaging and quantitative analysis of NP uptake within close-to-native cells, offering new insights into NP trafficking and cellular responses relevant to nanomedicine development.

Indexed as

Cryoelectron MicroscopyNanoparticlesTomography, X-RayAnimalsCell Line, TumorFemaleImaging, Three-DimensionalMiceMicroscopy, Fluorescencecryo‐FIBSEMcryo‐FMcryogenic correlative light and electron microscopy (cryo‐CLEM)cryogenic correlative light and X‐ray tomography (cryo‐CLXT)cryogenic soft X‐ray tomography (cryo‐SXT)nanoparticle intracellular uptake and trafficking

Identifiers

PMID40887945
PMCPMC12803693

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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.