Nanobody-fotosensibilisatorconjugaten voor gerichte fotodynamische therapie

Abstract

OBJECTIVE To improve photodynamic therapy (PDT). This therapy induces cell death through light-activation of a photo-sensitizer [PS]. Targeted delivery of PS via monoclonal antibodies has improved tumour selectivity, but these conjugates have long half-lives, leading to relatively long photosensitivity in patients. DESIGN AND METHODS In an attempt to target PS specifically to tumours 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). RESULTS These fluorescent conjugates allow the distinction of cell lines with different expression levels of EGFR and specifically induce cell death of EGFR-overexpressing cells at low nanomolar concentrations, while PS alone or the NB-PS conjugates in absence of light induce no toxicity. Delivery of PS using internalizing biparatopic NB-PS conjugates results in even more pronounced phototoxicities. CONCLUSION Altogether, EGFR targeted NB-PS conjugates are specific and potent, enabling the combination of molecular imaging with cancer therapy.