De Groof, Timo W. M. Mashayekhi, Vida Fan, Tian Shu Bergkamp, Nick D. Toraño, Javier Sastre van Senten, Jeffrey R. Heukers, Raimond Smit, Martine J. Oliveira, Sabrina Nanobody-Targeted Photodynamic Therapy Selectively Kills Viral GPCR-Expressing Glioblastoma Cells 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. 3 D cultures;photosensitizer IRDye 700DX;nanobody;near-infrared light;nanobodie;PDT;Diverse G protein-coupled receptors;Nanobody-Targeted Photodynamic Therapy Selectively Kills Viral GPCR-Expressing Glioblastoma Cells Photodynamic therapy;28-expressing glioblastoma cells;tumor 2019-06-05
    https://acs.figshare.com/articles/journal_contribution/Nanobody-Targeted_Photodynamic_Therapy_Selectively_Kills_Viral_GPCR-Expressing_Glioblastoma_Cells/8295554
10.1021/acs.molpharmaceut.9b00360.s001