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Issue 10, 2016
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A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy

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Abstract

In many cancers early intervention involves surgical resection of small localised tumour masses. Inadequate resection leads to recurrence whereas overzealous treatment can lead to organ damage. This work describes production of a HER2 targeting antibody Fab fragment dual conjugated to achieve both real time near-infrared fluorescent imaging and photodynamic therapy. The use of fluorescence emission from a NIR-dye could be used to guide resection of tumour bulk, for example during endoscopic diagnosis for oesophago-gastric adenocarcinoma, this would then be followed by activation of the photodynamic therapeutic agent to destroy untreated localised areas of cancer infiltration and tumour infiltrated lymph nodes. This theranostic agent was prepared from the Fab fragment of trastuzumab initially by functional disulfide re-bridging and site-specific click reaction of a NIR-dye. This was followed by further reaction with a novel pre-activated form of the photosensitiser chlorin e6 with the exposed fragments’ lysine residues. Specific binding of the theranostic agent was observed in vitro with a HER2 positive cell line and cellular near-infrared fluorescence was observed with flow cytometry. Specific photo-activity of the conjugates when exposed to laser light was observed with HER2 positive but not HER2 negative cell lines in vitro, this selectivity was not seen with the unconjugated drug. This theranostic agent demonstrates that two different photo-active functions can be coupled to the same antibody fragment with little interference to their independent activities.

Graphical abstract: A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy

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Publication details

The article was received on 06 May 2016, accepted on 01 Aug 2016 and first published on 02 Aug 2016


Article type: Paper
DOI: 10.1039/C6PP00139D
Citation: Photochem. Photobiol. Sci., 2016,15, 1227-1238
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    A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy

    H. Pye, M. A. Butt, H. W. Reinert, A. Maruani, J. P. M. Nunes, J. S. Marklew, M. Qurashi, L. Funnell, A. May, I. Stamati, R. Hamoudi, J. R. Baker, M. E. B. Smith, S. Caddick, M. P. Deonarain, G. Yahioglu, V. Chudasama and L. B. Lovat, Photochem. Photobiol. Sci., 2016, 15, 1227
    DOI: 10.1039/C6PP00139D

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