Photochemical internalization: A novel technology for targeted macromolecule therapy

Abstract

Photochemical internalization (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induces a release of macromolecules from their compartmentalization in endocytic vesicles. PCI has been shown to enhance the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus, oligonucleotides, and the chemotherapeuticum bleomycin. PCI has also been shown to enhance the treatment effect of targeted therapeutic macromolecules. The results show that PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that PCI may have a variety of useful applications for site-specific drug delivery, e.g., in gene therapy, vaccination, and cancer treatment. Our studies also indicate that PCI of bleomycin is superior to PDT in targeting the tumor periphery and that this is partly the cause of the improved treatment effect of PCI as compared to PDT.