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A photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has(More)
Photochemical internalization (PCI) is a novel technology of macromolecular delivery. By PCI, endocytosed membrane-impermeable therapeutic drugs are photochemically released from entrapment in endo-lysosomal compartments to the cytosol of target cells. In the present report, we describe the in vitro proof-of-concept for PCI of cetuximab-saporin, an(More)
A successful cure of cancer by biopharmaceuticals with intracellular targets is dependent on both specific and sufficient delivery of the drug to the cytosol or nuclei of malignant cells. However, cytosolic delivery and efficacy of membrane-impermeable cancer therapeutics are often hampered by the sequestration and degradation of the drugs in the(More)
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(More)
PDT in cancer therapy has been reviewed several times recently and many published reports have been showing promising results. The clinical approvals for PDT include curative treatment of early or superficial cancers and palliative treatment of more advanced disease. Still PDT has yet to become a widely used cancer treatment. This may partly be due to(More)
The utilisation of macromolecules in the therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. In many cases the targets of macromolecular(More)
BACKGROUND Photochemical internalization (PCI) is a modality for cytosolic release of drugs trapped in endocytic vesicles. The method is based upon photosensitizers localized in the membranes of endocytic vesicles which create membrane rupture upon light exposure by generating reactive oxygen species (ROS), predominantly singlet oxygen ((1)O(2)). METHODS(More)
A wide range of anti-cancer drugs are substrates of the ATP-binding cassette transporter ABCG2/CD338/BCRP/MXR, which is thought to play an important role in multi-drug resistance (MDR) and protection of cancer stem cells (CSC) against chemotherapeutics and photodynamic therapy (PDT). Hence, it is of importance to develop drugs that are not substrates of(More)
Drug resistance is a major problem for chemotherapy. Entrapment of anticancer drugs in endolysosomal compartments or active extrusions by plasma membrane proteins of the ATP-binding cassette (ABC) superfamily are important resistance mechanisms. This study evaluated photochemical internalization (PCI) of membrane-impermeable macromolecules that are not the(More)
We have used the site specific and light-depended drug delivery method photochemical internalization (PCI) to release an immunotoxin (IT), targeting the CD44 receptor, into the cytosol of target cells. The IT consisted of a pan CD44 mAb (clone IM7) bound to the ribosome inactivating protein (RIP) saporin by a biotin-streptavidin linker named IM7-saporin.(More)