Nanobody-Targeted Photodynamic Therapy Selectively Kills Viral GPCR-Expressing Glioblastoma Cells.
Mol Pharm
; 16(7): 3145-3156, 2019 07 01.
Article
en En
| MEDLINE
| ID: mdl-31244224
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fotoquimioterapia
/
Proteínas Virales
/
Neoplasias Encefálicas
/
Fármacos Fotosensibilizantes
/
Compuestos de Organosilicio
/
Glioblastoma
/
Inmunoconjugados
/
Receptores de Quimiocina
/
Anticuerpos de Dominio Único
/
Indoles
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article