Photochemical internalization: a new tool for drug delivery.
The utilisation 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 targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. In many 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 internalisation (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), DNA delivered as gene-encoding plasmids or by means of adenovirus or adeno-associated virus, peptide nucleic acids (PNAs) and chemotherapeutic agents such as bleomycin and in some cases doxorubicin. PCI of PNA may be of particular importance due to the low therapeutic efficacy of PNA in the absence of an efficient delivery technology and the 10-100-fold increased efficacy in combination with PCI. The efficacy and specificity of PCI of macromolecular therapeutics has been improved by combining the macromolecules with targeting moieties, such as the epidermal growth factor. 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.
Berg
Kristian
K
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. kristian.berg@rr-research.no
Folini
Marco
M
Prasmickaite
Lina
L
Selbo
Pål Kristian
PK
Bonsted
Anette
A
Engesaeter
Birgit Ø
BØ
Zaffaroni
Nadia
N
Weyergang
Anette
A
Dietze
Andreas
A
Maelandsmo
Gunhild M
GM
Wagner
Ernst
E
Norum
Ole-Jacob
OJ
Høgset
Anders
A
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008027:Light; D046911:Macromolecular Substances / Q000008:administration & dosage / Q000737:chemistry; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D022161:Transport Vesicles / Q000378:metabolism
D046911:Macromolecular Substances; D004364:Pharmaceutical Preparations; D017319:Photosensitizing Agents