Photochemical internalization (PCI): A novel technology for activation of endocytosed therapeutic agents
Journal
Medical Laser Application
Journal Volume
21
Journal Issue
4
Pages
239-250
Date Issued
2006
Author(s)
Berg K
Høgset A
Prasmickaite L
Weyergang A
Bonsted A
Dietze A
Bown S
Norum O.-J
Møllergård H.M.T
Selbo P.K.
Abstract
The utilization of macromolecules in the therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve the targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. In most cases the targets of macromolecular therapeutics are intracellular. However, degradation of macromolecules in endocytic vesicles after uptake by endocytosis is a major intracellular barrier for the therapeutic application of macromolecules having intracellular targets of action. Photochemical internalization (PCI) is a novel technology for the release of endocytosed macromolecules into the cytosol. The technology is based on the activation by light of photosensitizers located in endocytic vesicles to induce the release of macromolecules from the endocytic vesicles. Thereby endocytosed molecules can be released to reach their target of action before being degraded in lysosomes. PCI has been shown to stimulate intracellular delivery of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), RIP-based immunotoxins, DNA delivered as gene-encoding plasmids or by means of adenoviruses or adeno-associated viruses, peptide-nucleic acids and chemotherapeutic agents such as bleomycin. The efficacy and specificity of PCI of macromolecular therapeutic agents have been improved by combining the macromolecules with targeting moieties, such as the epidermal growth factor. Several animal models have been used for in vivo documentation of the PCI principle. Recent results also indicate that PCI may reverse doxorubicin resistance or be utilized to circumvent multidrug resistance. In general, PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that it may have a variety of useful applications for site-specific drug delivery, as for example in gene therapy, vaccination and cancer treatment. ? 2006 Elsevier GmbH. All rights reserved.
Subjects
Drug delivery; Gene therapy; Macromolecule; Peptide nucleic acid; Photochemical internalization; Photodynamic; Photosensitizer; Protein toxin
SDGs
Other Subjects
Cells; Controlled drug delivery; Macromolecules; Oncology; Patient treatment; Photosensitizers; Gene therapy; Peptide nucleic acid; Photochemical internalization; Photodynamics; Protein toxin; Photochemical reactions; acridine orange; aluminium phthalocyanine; antiinfective agent; bleomycin; disulphonated aluminium phthalocyanine; doxorubicin; epidermal growth factor; gelonin; herpes simplex virus thymidine kinase; interleukin 12; lutetium texaphyrin; nile blue sulfate; oligonucleotide; peptide nucleic acid; photosensitizing agent; phthalocyanine; polymer; porphyrin; porphyrin derivative; ribosome inactivating protein; ribosome inactivating protein type 1; saporin; silicone phthalocyanine; tetraphenylporphyrin derivative; tetrasulphonated aluminium phthalocyanine; thymidine kinase; tin ethyletiopurpurin; unclassified drug; unindexed drug; uroporphyrin; vaccine; article; cancer; cancer therapy; cell activation; cell secretion; cytosol; cytotoxicity; drug delivery system; drug resistance; endosome; gene targeting; gene therapy; human; lysosome; macromolecule; multidrug resistance; nonhuman; nonviral gene delivery system; photochemical internalization; photodynamic therapy; vaccination; viral gene delivery system; virus vector
Type
journal article