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

Authors

Xuan Zhang
Sathvik Shastry
Stephen E Bradforth
Jay L Nadeau

Publication/Presentation Date

1-7-2015

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.

Volume

7

Issue

1

First Page

240

Last Page

251

ISSN

2040-3372

Published In/Presented At

Zhang, X., Shastry, S., Bradforth, S. E., & Nadeau, J. L. (2015). Nuclear uptake of ultrasmall gold-doxorubicin conjugates imaged by fluorescence lifetime imaging microscopy (FLIM) and electron microscopy. Nanoscale, 7(1), 240–251. https://doi.org/10.1039/c4nr04707a

Disciplines

Medical Education | Medicine and Health Sciences

PubMedID

25407725

Department(s)

USF-LVHN SELECT Program, USF-LVHN SELECT Program Students

Document Type

Article