title: 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 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.
authors.affiliation: Molecular Oncology, Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
authors.forename: Raimond
authors.initials: R
authors.lastname: Heukers
authors.affiliation: Molecular Oncology, Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
authors.forename: Paul M P
authors.initials: PM
authors.lastname: van Bergen en Henegouwen
authors.affiliation: Molecular Oncology, Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: s.oliveira@uu.nl.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D066246:ErbB Receptors / Q000276:immunology; D051379:Mice; D041681:NIH 3T3 Cells; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D061905:Single-Domain Antibodies
chemical_list: D017319:Photosensitizing Agents; D061905:Single-Domain Antibodies; D066246:ErbB Receptors
keywords: EGFR; Molecular imaging; Nanobody; Nanomedicine; Photodynamic therapy; Targeted photosensitizer; VHH