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

Content Provider	Semantic Scholar
Author	Zhang, Xuan Shastry, Sathvik Bradforth, Stephen E. Nadeau, Jay L.
Copyright Year	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.
Starting Page	597
Ending Page	600
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.rsc.org/suppdata/nr/c4/c4nr04707a/c4nr04707a1.pdf
Alternate Webpage(s)	http://pubs.rsc.org/en/content/getauthorversionpdf/C4NR04707A
PubMed reference number	25407725v1
Alternate Webpage(s)	https://doi.org/10.1039/c4nr04707a
DOI	10.1039/c4nr04707a
Journal	Nanoscale
Volume Number	7
Issue Number	1
Language	English
Access Restriction	Open
Subject Keyword	Cell Nucleus Cessation of life Diameter (qualifier value) Doxorubicin Electron Microscopy Gold Immunostimulating conjugate (antigen) Malignant Neoplasms Microscopy, Fluorescence Subcellular structure Tissue membrane
Content Type	Text
Resource Type	Article