Photochemical internalization (PCI)--a novel technology for release of macromolecules from endocytic vesicles.
The utilisation of macromolecules in therapy of cancer and other diseases is becoming increasingly relevant. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents or DNA complexes for clinical applications. To achieve the expected biological effect of these macromolecules in many cases internalization to the cell cytosol is crucial. A number of different methods for internalization of membrane impermeable molecules has been established, including electroporation, liposome fusion, antibodies/targeting ligands as protein carriers and the utilisation of various types of vectors such as cationic polymers and viruses, for gene therapy. Although new delivery systems have improved the cellular uptake of macromolecules, tissue penetration, cellular uptake and efficient transfer of the molecules into the cytosol of the target cell are still fundamental obstacles. At an intracellular level, the most fundamental obstruction for cytosolic release of the therapeutic molecule is the membrane-barrier of the endocytic vesicles. 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 induce a release of macromolecules from their compartmentalization in endocytic vesicles. PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including proteins, peptides, and DNA delivered as a complex with cationic polymers or incorporated in adenovirus. The basis as well as the utilization of this technology will be briefly reviewed in this paper.
Berg
Kristian
K
Department of Biophysics, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. kristian.berg@labmed.uio.no
Prasmickaite
Lina
L
Selbo
Pål Kristian
PK
Hellum
Marit
M
Bonsted
Anette
A
Høgset
Anders
A
D003196:Computer Graphics; D003600:Cytosol / Q000378:metabolism; D016503:Drug Delivery Systems; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D009369:Neoplasms / Q000188:drug therapy; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000627:therapeutic use; D022161:Transport Vesicles / Q000378:metabolism*
D046911:Macromolecular Substances; D017319:Photosensitizing Agents