Nanobody-Targeted Photodynamic Therapy Selectively Kills Viral GPCR-Expressing Glioblastoma Cells

Timo W.M. De Groof, Vida Mashayekhi, Tian Shu Fan, Nick D. Bergkamp, Javier Sastre Toraño, Jeffrey R. Van Senten, Raimond Heukers, Martine J. Smit*, Sabrina Oliveira

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Photodynamic therapy (PDT) eradicates tumors by the local activation of a photosensitizer with near-infrared light. One of the aspects hampering the clinical use of PDT is the poor selectivity of the photosensitizer. To improve this, we have recently introduced a new approach for targeted PDT by conjugating photosensitizers to nanobodies. Diverse G protein-coupled receptors (GPCRs) show aberrant overexpression in tumors and are therefore interesting targets in cancer therapy. Here we show that GPCR-targeting nanobodies can be used in targeted PDT. We have developed a nanobody binding the extracellular side of the viral GPCR US28, which is detected in tumors like glioblastoma. The nanobody was site-directionally conjugated to the water-soluble photosensitizer IRDye700DX. This nanobody-photosensitizer conjugate selectively killed US28-expressing glioblastoma cells both in 2D and 3D cultures upon illumination with near-infrared light. This is the first example employing a GPCR as target for nanobody-directed PDT. With the emerging role of GPCRs in cancer, this data provides a new angle for exploiting this large family of receptors for targeted therapies.

Original languageEnglish
JournalMolecular Pharmaceutics
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • cancer
  • G protein-coupled receptors
  • glioblastoma
  • nanobody
  • photodynamic therapy
  • targeted photosensitizer
  • US28

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