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  • Title: Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF-saporin.
    Author: Weyergang A, Selbo PK, Berg K.
    Journal: J Control Release; 2006 Mar 10; 111(1-2):165-73. PubMed ID: 16466823.
    Abstract:
    Epidermal growth factor receptor (EGFR) targeting has become a major field in both cancer research and therapy. In the present study an EGF-saporin affinity toxin has been established and evaluated in two EGFR overexpressing cancer cell lines. The binding of saporin to EGF did not influence the ribosome-inactivating activity of saporin as measured by a luminescence based reticulocyte lysate assay. Control experiments, using untargeted saporin, EGFR-negative cell lines and competition with EGF and anti-EGFR antibody were used to document selective uptake of the affinity toxin. One limitation in administration of macromolecular-drugs is lysosomal degradation. Photochemical internalization (PCI) is a modality for cytosolic release of macromolecules based on photochemical rupture of endocytic membranes and subsequent drug release. It was shown that PCI increases the toxicity of EGF-saporin significantly in EGFR-positive cells. EGF binding to saporin enhanced the PCI-induced cytotoxicity in NuTu-19 cells about 1000-fold when the photochemical treatment alone killed 50% of the cells. In conclusion, PCI of EGF-saporin is a promising method for increasing the efficiency of protein toxin-based cancer therapies. PCI of targeting toxins also exert a triple tumour-selectivity; utilization of an affinity toxin, preferential accumulation of the photosensitizer in neoplastic lesions, and site-directed light activation.
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