Three-dimensional imaging and uptake of the anticancer drug combretastatin in cell spheroids and photoisomerization in gels with multiphoton excitation

Scherer, KM; Bisby, RH; Botchway, SW; Hadfield, JA; Haycock, JW; Parker, AW

Abstract

The uptake of E-combretastatins, potential pro-drugs of the anticancer Z-isomers, into multicellular spheroids has been imaged by intrinsic fluorescence in three dimensions using two-photon excited fluorescence lifetime imaging with 625 nm ultrafast femtosecond laser pulses. Uptake is initially observed at the spheroid periphery but extends to the spheroid core within 30 minutes. Using agarose gels as a three-dimensional model, the conversion of Z(trans) E(cis) via two-photon photoisomerization is demonstrated and the location of this photochemical process may be selected precisely within the micron scale in all three dimensions at depths up to almost 2 mm. We discuss these results for enhanced tissue penetration at longer near-infrared wavelengths for cancer therapy and up to three-photon excitation and imaging using 930 nm laser pulses with suitable combretastatin analogues.

• Journal Article Type: Article
• Acceptance Date: May 28, 2015
• Online Publication Date: Jul 6, 2015
• Publication Date: Jul 6, 2015
• Deposit Date: Jun 1, 2015
• Publicly Available Date: Apr 5, 2016
• Journal: Journal of Biomedical Optics
• Print ISSN: 1083-3668
• Electronic ISSN: 1560-2281
• Publisher: Society of Photo-optical Instrumentation Engineers
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 7
• Pages: 78003
• DOI: https://doi.org/10.1117/1.JBO.20.7.078003
• Publisher URL: http://dx.doi.org/10.1117/1.JBO.20.7.078003
• Related Public URLs: http://spie.org/x866.xml
• Additional Information: Grant Number: ST/K001914/1