Jump to main content
Jump to site search

Issue 1, 2015
Previous Article Next Article

Nuclear uptake of ultrasmall gold-doxorubicin conjugates imaged by fluorescence lifetime imaging microscopy (FLIM) and electron microscopy

Author affiliations

Abstract

Fluorescence lifetime imaging microscopy (FLIM) has been used to image free and encapsulated doxorubicin (Dox) uptake into cells, since interaction of Dox with DNA leads to a characteristic lifetime change. However, none of the reported Dox conjugates were able to enter cell nuclei. In this work, we use FLIM to show nuclear uptake of 2.7 nm mean diameter Au nanoparticles conjugated to Dox. The pattern of labelling differed substantially from what was seen with free Dox, with slower nuclear entry and stronger cytoplasmic labelling at all time points. As the cells died, the pattern of labelling changed further as intracellular structures disintegrated, consistent with association of Au–Dox to membranes. The patterns of Au distribution and intracellular structure changes were confirmed using electron microscopy, and indicate different mechanisms of cytotoxicity with stable Au–Dox conjugates compared to Dox alone. Such conjugates are promising tools for overcoming resistance in Dox-resistant cancers.

Graphical abstract: Nuclear uptake of ultrasmall gold-doxorubicin conjugates imaged by fluorescence lifetime imaging microscopy (FLIM) and electron microscopy

Back to tab navigation

Supplementary files

Publication details

The article was received on 15 Aug 2014, accepted on 06 Nov 2014 and first published on 10 Nov 2014


Article type: Paper
DOI: 10.1039/C4NR04707A
Author version
available:
Download author version (PDF)
Nanoscale, 2015,7, 240-251

  •   Request permissions

    Nuclear uptake of ultrasmall gold-doxorubicin conjugates imaged by fluorescence lifetime imaging microscopy (FLIM) and electron microscopy

    X. Zhang, S. Shastry, S. E. Bradforth and J. L. Nadeau, Nanoscale, 2015, 7, 240
    DOI: 10.1039/C4NR04707A

Search articles by author

Spotlight

Advertisements