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Photochemical Internalization

A Novel Technology for Delivery of Macromolecules into Cytosol¹

Departments of Biophysics [K. B., P. K. S., L. P., T. E. T., J. M., S. K., H. A., G. H. R., S. K. R., A. H.], Biochemistry [K. S.], Immunology [G. G.], and Tumour Biology [Ø. F.], Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo 3, Norway

The therapeutic usefulness of macromolecules, such as in gene therapy, is often limited by an inefficient transfer of the macromolecule to the cytosol and a lack of tissue-specific targeting. The possibility of photochemically releasing macromolecules from endosomes and lysosomes into the cytosol was examined. Endocytosed macromolecules and photosensitizer were exposed to light and intracellular localization and the expression of macomolecules in the cytosol was analyzed. This novel technology, named photochemical internalization (PCI), was found to efficiently deliver type I ribosome-inactivating proteins, horseradish peroxidase, a p21^ras-derived peptide, and a plasmid encoding green fluorescent protein into cytosol in a light-dependent manner. The results presented here 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.

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