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

Pieter B.A.A. Van Driel, Martin C. Boonstra, Maxime D. Slooter, Raimond Heukers, Marieke A. Stammes, Thomas J.A. Snoeks, Henriette S. De Bruijn, Paul J. Van Diest, Alexander L. Vahrmeijer, Paul M.P. Van Bergen En Henegouwen, Cornelis J.H. Van De Velde, Clemens W.G.M. Löwik, Dominic J. Robinson, Sabrina Oliveira

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish (US)
Pages (from-to)93-105
Number of pages13
JournalJournal of Controlled Release
Volume229
DOIs
StatePublished - May 10 2016

Keywords

  • EGFR
  • Head and neck cancer
  • Nanobody or VHH
  • Photodynamic therapy
  • Quantitative fluorescence spectroscopy
  • Tumor targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer'. Together they form a unique fingerprint.

Cite this