Nanobody–photosensitizer conjugates for targeted photodynamic therapy

Abstract Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an...

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Bibliographic Details
Published in:Nanomedicine 2014-10, Vol.10 (7), p.1441-1451
Main Authors: Heukers, Raimond, MSc, van Bergen en Henegouwen, Paul M.P., PhD, Oliveira, Sabrina, PhD
Format: Article
Language:English
Subjects:
Animals
Coculture Techniques
EGFR
Internal Medicine
Mice
Molecular imaging
Nanobody
Nanomedicine
NIH 3T3 Cells
Photochemotherapy
Photodynamic therapy
Photosensitizing Agents - chemistry
Receptor, Epidermal Growth Factor - immunology
Single-Domain Antibodies
Targeted photosensitizer
VHH
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Summary:Abstract Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt to target PS specifically to tumors and to accelerate PS clearance, we have developed new conjugates consisting of nanobodies (NB) targeting the epidermal growth factor receptor (EGFR) and a traceable PS (IRDye700DX). These fluorescent conjugates allow the distinction of cell lines with different expression levels of EGFR. Results show that these conjugates specifically induce cell death of EGFR overexpressing cells in low nanomolar concentrations, while PS alone or the NB–PS conjugates in the absence of light induce no toxicity. Delivery of PS using internalizing biparatopic NB–PS conjugates results in even more pronounced phototoxicities. Altogether, EGFR-targeted NB–PS conjugates are specific and potent, enabling the combination of molecular imaging with cancer therapy. From the Clinical Editor This study investigates the role of EGFR targeting nanobodies to deliver traceable photosensitizers to cancer molecules for therapeutic exploitation and concomitant imaging. Altogether, EGFR-targeted NB–PS conjugates combine molecular imaging with cancer therapy, the method is specific and potent, paving the way to clinical application of this technology.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2013.12.007