Cell-Nanoparticle Interactions at (Sub)-Nanometer Resolution Analyzed by Electron Microscopy and Correlative Coherent Anti-Stokes Raman Scattering

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http://hdl.handle.net/10138/301190

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Saarinen , J K S , Gütter , F , Lindman , M M , Agopov , M , Fraser-Miller , S J , Scherließ , R , Jokitalo , E , Almeida Santos , H , Peltonen , L , Isomäki , A & Strachan , C J 2019 , ' Cell-Nanoparticle Interactions at (Sub)-Nanometer Resolution Analyzed by Electron Microscopy and Correlative Coherent Anti-Stokes Raman Scattering ' , Biotechnology Journal , vol. 14 , no. 4 , 1800413 . https://doi.org/10.1002/biot.201800413

Title: Cell-Nanoparticle Interactions at (Sub)-Nanometer Resolution Analyzed by Electron Microscopy and Correlative Coherent Anti-Stokes Raman Scattering
Author: Saarinen, Jukka Kalle Samuel; Gütter, Friederike; Lindman, Mervi M; Agopov, Mikael; Fraser-Miller, Sara J.; Scherließ, Regina; Jokitalo, Eija; Almeida Santos, Helder; Peltonen, Leena; Isomäki, Antti; Strachan, Clare J.
Contributor: University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Drug Research Program
University of Helsinki, Drug Research Program
University of Helsinki, Department of Anatomy
University of Helsinki, Drug Research Program
Date: 2019-04
Language: eng
Number of pages: 10
Belongs to series: Biotechnology Journal
ISSN: 1860-6768
URI: http://hdl.handle.net/10138/301190
Abstract: A wide variety of nanoparticles are playing an increasingly important role in drug delivery. Label-free imaging techniques are especially desirable to follow the cellular uptake and intracellular fate of nanoparticles. The combined correlative use of different techniques, each with unique advantages, facilitates more detailed investigation about such interactions. The synergistic use of correlative coherent anti-Stokes Raman scattering and electron microscopy (C-CARS-EM) imaging offers label-free, chemically-specific, and (sub)-nanometer spatial resolution for studying nanoparticle uptake into cells as demonstrated in the current study. Coherent anti-Stokes Raman scattering (CARS) microscopy offers chemically-specific (sub)micron spatial resolution imaging without fluorescent labels while transmission electron microscopy (TEM) offers (sub)-nanometer scale spatial resolution and thus visualization of precise nanoparticle localization at the sub-cellular level. This proof-of-concept imaging platform with unlabeled drug nanocrystals and macrophage cells revealed good colocalization between the CARS signal and electron dense nanocrystals in TEM images. The correlative TEM images revealed subcellular localization of nanocrystals inside membrane bound vesicles, showing multivesicular body (MVB)-like morphology typical for late endosomes (LEs), endolysosomes, and phagolysosomes. C-CARS-EM imaging has much potential to study the interactions between a wide range of nanoparticles and cells with high precision and confidence.
Subject: FLUORESCENCE
IN-VITRO
LASER
LOCALIZATION
SPECTRA
SPECTROSCOPY
TOOL
cell imaging
cellular nanoparticle uptake
coherent anti-Stokes Raman scattering (CARS) microscopy
drug nanocrystals
non-linear imaging
1182 Biochemistry, cell and molecular biology
116 Chemical sciences
317 Pharmacy
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