High-Contrast Imaging of Nanodiamonds in Cells by Energy Filtered and Correlative Light-Electron Microscopy: Toward a Quantitative Nanoparticle-Cell Analysis

Nano Letters
Shen HanIngo Lieberwirth

Abstract

Fluorescent nanodiamonds (fNDs) represent an emerging class of nanomaterials offering great opportunities for ultrahigh resolution imaging, sensing and drug delivery applications. Their biocompatibility, exceptional chemical and consistent photostability renders them particularly attractive for correlative light-electron microscopy studies providing unique insights into nanoparticle-cell interactions. Herein, we demonstrate a stringent procedure to image and quantify fNDs with a high contrast down to the single particle level in cells. Individual fNDs were directly visualized by energy-filtered transmission electron microscopy, that is, inside newly forming, early endosomal vesicles during their cellular uptake processes as well as inside cellular organelles such as a mitochondrion. Furthermore, we demonstrate the unequivocal identification, localization, and quantification of individual fNDs in larger fND clusters inside intracellular vesicles. Our studies are of great relevance to obtain quantitative information on nanoparticle trafficking and their various interactions with cells, membranes, and organelles, which will be crucial to design-improved sensors, imaging probes, and nanotherapeutics based on quantitative data.

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Citations

Jan 31, 2020·Nanomedicine·Robert A Yokel
Jul 15, 2020·Nanomedicine·Yen-Yiu LiuHuan-Cheng Chang
Sep 26, 2020·Biotechnology Journal·Philipp ReineckGary Bryant
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Neeraj PrabhakarJessica M Rosenholm
Jun 30, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yingke WuTanja Weil
Nov 30, 2021·Analytical Chemistry·Aldona MzykRomana Schirhagl

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Methods Mentioned

BETA
transmission electron microscopy
imaging techniques
electron microscopy
dynamic light scattering
fluorescence microscopy
fluorescence imaging

Software Mentioned

CLEM
EFTEM

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