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Nanobody-Targeted Photodynamic Therapy Selectively Kills Viral GPCR-Expressing Glioblastoma Cells
journal contribution
posted on 2019-06-05, 00:00 authored by 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 OliveiraPhotodynamic
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.