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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.241 5年影响因子: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.v25.i1-2.330
pages 521-536

Photochemical Internalization (PCI): A New Modality for Light Activation of Endocytosed Therapeuticals

Andreas Dietze
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Pal Kristian Selbo
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Lina Prasmickaite
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Anette Weyergang
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Anette Bonsted
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Birgit Engesater
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Anders Hogset
PCI Biotech AS, Hoffsveien 48, N-0377 Oslo, Norway
Kristian Berg
Oslo University Hospital, The Norwegian Radium Hospital, Dept. of Radiation Biology, Oslo, 0379, Norway

ABSTRACT

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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