Photochemical internalisation in drug and gene delivery.

This article reviews a novel technology, named photochemical internalisation (PCI), for light-induced delivery of genes, proteins and many other classes of therapeutic molecules. 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. PCI is based upon the light activation of a drug (a photosensitizer) specifically locating in the membrane of endocytic vesicle 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. The fact that this effect is induced by illumination means that the biological activity of the molecules can be activated at specific sites in the body, simply by illuminating the relevant region. We have used the PCI strategy to obtain light-induced delivery of a variety of molecules, including proteins, peptides, oligonucleotides, genes and low molecular weight drugs. In several cases, a >100-fold increase in biological activity has been observed.

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