EGFR targeted nanobody–photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer

• DOI: 10.1016/j.jconrel.2016.03.014
• Publication Date: 2016-03-15T07:36:40Z
• Authors: Pieter B.A.A. van...; Martin C. Boonstra; Maxime D. Slooter; Raimond Heukers; Marieke A. Stammes; Thomas J.A. Snoeks; Henriette S. de B...; Paul J. van Diest; Alexander L. Vahr...; Paul M.P. van Ber...; Cornelis J.H. van...; Clemens W.G.M. Löwik; Dominic J. Robinson; Sabrina Oliveira
• Keywords: Phototoxicity; Targeted Therapy

Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head neck cancers. Yet, common PS lack tumor specificity, which leads collateral damage normal tissues. Targeted delivery via antibodies pre-clinically improved selectivity. However, have long half-lives relatively poor tissue penetration, could limit therapeutic efficacy lead photosensitivity. Here, in this feasibility study, we evaluate at the pre-clinical level recently introduced format targeted PDT, employs nanobodies as targeting agents water-soluble (IRDye700DX) that is traceable optical imaging. In vitro, solely binds cells phototoxicity on overexpressing epidermal growth factor receptor (EGFR), when conjugated EGFR nanobodies. To investigate whether new PDT capable inducing selective vivo, was applied an orthotopic mouse model with illumination 1h post-injection nanobody-PS conjugates, selected from quantitative fluorescence spectroscopy measurements. parallel, reference, antibody-PS conjugate, performed 24h post-injection. Importantly, conjugates led extensive necrosis (approx. 90%) almost no toxicity healthy tissues, observed histology after PDT. Overall, results show these are able induce vivo. Additional studies now needed assess full potential approach improving