Photochemical internalization (PCI) is a new technology, where certain photosensitizing substances (photosensitizers) are used to improve the utilization of macromolecules for cancer therapy, in a site-specific manner. Degradation of macromolecules in endocytic vesicles after uptake by endocytosis is a major intracellular barrier for the therapeutic application of molecules having intracellular targets of action. PCI is based on the light activation of photosensitizers specifically located in the membrane of endocytic vesicles inducing the rupture of this membrane upon illumination. Thereby endocytosed molecules can be released to reach their target of action before being degraded in lysosomes. This 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), immunotoxins, gene-encoding plasmids, adenovirus, peptidenucleic acids, and the chemotherapeuticum bleomycin. In several cases up to a 100-fold increase in biological activity has been observed. This article reviews the background and present status of PCI.
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