title: Fluorescence intensity and lifetime imaging of free and micellar-encapsulated doxorubicin in living cells.
abstract: Frequency domain fluorescence lifetime imaging microscopy (FLIM) has been used in combination with laser scanning confocal microscopy to study the cellular uptake behavior of the antitumor drug doxorubicin (DOX) and micellar-encapsulated DOX (PLyAd-DOX). The endocytosis uptake process of PLyAd-DOX was monitored over 72 hours using confocal microscopy, with a maximum fluorescence recorded at incubation periods around 24 hours. The micellar structure was not found to release the encapsulated DOX during the time course of imaging. FLIM revealed single lifetime distributions of PLyAd-DOX during accumulation in the cytoplasm. The free DOX in contrast was observed both in the cytoplasm and the nuclear domain of the cell, showing bimodal lifetime distributions. There was a marked dependence of the measured free-DOX lifetime on concentration within the cell, in contrast to reference experiments in aqueous solution, where no such dependence was found. The results suggest the formation of macromolecular structures inside the living cells.
authors.affiliation: Department of Chemical Engineering, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Dai
authors.forename: Zhilian
authors.initials: Z
authors.lastname: Yue
authors.forename: Mark E
authors.initials: ME
authors.lastname: Eccleston
authors.forename: Johannes
authors.initials: J
authors.lastname: Swartling
authors.forename: Nigel K H
authors.initials: NK
authors.lastname: Slater
authors.forename: Clemens F
authors.initials: CF
authors.lastname: Kaminski
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D008856:Microscopy, Fluorescence; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D004317:Doxorubicin