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Uptake of gold nanoparticles in healthy and tumor cells visualized by nonlinear optical microscopy.

Authors
  • Rago, Gianluca
  • Bauer, Brigitte
  • Svedberg, Fredrik
  • Gunnarsson, Linda
  • Ericson, Marica B
  • Bonn, Mischa
  • Enejder, Annika
Type
Published Article
Journal
The Journal of Physical Chemistry B
Publisher
American Chemical Society
Publication Date
May 05, 2011
Volume
115
Issue
17
Pages
5008–5016
Identifiers
DOI: 10.1021/jp2009012
PMID: 21469683
Source
Medline
License
Unknown

Abstract

Understanding the mechanism underlying the interactions between inorganic nanostructures and biological systems is crucial for several rapidly growing fields that rely on nano-bio interactions. In particular, the further development of cell-targeted drug delivery using metallic nanoparticles (NP) requires new tools for understanding the mechanisms triggered by the contact of NPs with membranes in different cells at the subcellular level. Here we present a novel concept of multimodal microscopy, enabling three-dimensional imaging of the distribution of gold NPs in living, unlabeled cells. Our approach combines multiphoton induced luminescence (MIL) with coherent anti-Stokes Raman scattering (CARS) microscopy. Comparison with transmission electron microscopy (TEM) reveals in vivo sensitivity down to the single nanostructure. By monitoring the incorporation of NPs in human healthy epidermal keratinocytes and squamous carcinoma cells (SCC), we address the feasibility of noninvasive delivery of NPs for therapeutic purposes. While neutralizing PEG coating was confirmed to prevent NP integration in SCCs, an unexpectedly efficient integration of NPs into keratinocytes was observed. These results, independently validated using TEM, demonstrate the need for advanced surface modification protocols to obtain tumor selectivity for NP delivery. The CARS/MIL microscopy platform presented here is thus a promising tool for noninvasive study of the interaction between NPs and cell.

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