Light-direction shows promise for siRNA therapeutics targeting
PCI Biotech’s novel photochemical drug delivery technology triggers targeted release of siRNA from nanogel carriers
Atlanta, May 19, 2009 – The targeted delivery of small interfering RNA (siRNA) therapeutics carried into cells by nanoparticles could be greatly enhanced by a light-activated system, according to a new study announced by PCI-Biotech at BIO2009.
siRNA therapeutics work by targeting and silencing specific genes involved in disease and are being investigated for treatment of a wide range of diseases from viral infections to cancer. The study, published in the journal Advanced Functional Materials, shows that the photochemical internalization (PCI) technology developed by PCI Biotech of Oslo, Norway, significantly enhances the gene silencing effects of siRNA in human cancer cells.
Researchers demonstrated the potential of PCI by treating cells that stably express the firefly luciferase gene with siRNA molecules trapped in a nanoscopic dextran (carbohydrate) gel. These complexes resulted in only modest luciferase silencing below 50%, depending on the concentration of nanogel used. But when the photosensitizer was added and activated by light, luciferase production was reduced up to ~80%.
In the cell, siRNA-nanogels are trafficked to vesicles called endosomes, where they become susceptible to attack by enzymes. The photosensitizer causes these vesicles to burst, allowing the siRNA molecules to escape to the surrounding cell cytosol before they can be degraded.
Koen Raemdonck, lead author of the study based at Ghent University in Belgium, comments: "Our main goal was to have our degradable nanogel particles intact inside the cytosol – to obtain a time-controlled release of siRNA. Endosomal vesicles are a real barrier for efficient drug release and so the reason we turned to PCI was to breach this barrier. We need to optimise the delivery concept before we can go from cell culture to in vivo, but I think in the future it has the potential to be used for systemic treatment as well as for more local delivery of drug molecules."
Dr. Anders Høgset, Chief Scientific Officer of PCI Biotech, adds: “The results in this study clearly show that PCI can substantially improve the delivery of nanoparticles to cells. The study thus confirms the wide potential of the PCI technology in nanomedicine, an important area in the development of advanced future therapies for a variety of diseases. The study also adds nicely to earlier studies demonstrating PCI’s great potential in delivery of siRNA, a class of molecules having an extraordinary therapeutic potential, the realization of which is still severely hampered by the lack of proper delivery systems.”
For more information visit: www.pcibiotech.com
Contact information:
PCI Biotech Holding ASA, Hoffsveien 48, N-0377 Oslo
Per Walday, CEO
Email: pw@pcibiotech.no
Mobil: +47 917 93 429