Journal Article

FZJ-2026-05233

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cryo-Electron Microscopy and Confocal Microscopy to Study the Pathway of Ultrasmall Gold Nanoparticles Inside Cells

Berkamp, S.FZJ* ; Białas, N. ; Loza, K. ; Sundermeyer, P.FZJ* ; Heggen, M.FZJ* ; Wolff, N. ; Epple, M. (Corresponding author)

2026
ACS Publications Washington, DC

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Please use a persistent id in citations: doi:10.1021/acsanm.6c03897

Abstract: The cellular uptake and intracellular distribution of fluorescently labeled ultrasmall gold nanoparticles (∼2 nm) inhuman RPE-1 cells were investigated by a complementary combination of confocal laser scanning microscopy (CLSM), structuredillumination microscopy (SIM), and cryo-electron microscopy (cryo-EM). The nanoparticles were synthesized by a modified Brust–Schiffrin route, functionalized with glutathione, and covalently labeled with AlexaFluor-647, enabling fluorescence-based tracking.High-resolution transmission electron microscopy showed a narrow particle size distribution with an average core diameter of 2.3 nm.Live-cell CLSM and SIM imaging revealed intracellular nanoparticle-associated fluorescence and pronounced colocalization withlysosomes, consistent with accumulation along the endolysosomal pathway. SIM provided an enhanced spatial resolution compared toCLSM, allowing a more detailed visualization of the intracellular nanoparticle localization. Notably, in addition to endolysosomallocalization, ultrasmall gold nanoparticles were occasionally observed inside the cell nucleus. Correlative light and cryo-electrontomography further enabled direct visualization of the electron-dense gold nanoparticles within vitrified cellular lamellae at near-nativeconditions. Some nanoparticles were found inside a multi-vesicular body, several large clusters of nanoparticles in a functional lysosome,and single nanoparticles and clusters in a late endosome or early lysosome. No nanoparticles were observed inside the nucleus by cryo-EM

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Contributing Institute(s):

1. Strukturbiologie (ER-C-3)

Research Program(s):

1. 5352 - Understanding the Functionality of Soft Matter and Biomolecular Systems (POF4-535) (POF4-535)
2. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2026

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Engineering, Computing and Technology ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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