like molecular dynamics simulations,
to
try to model assembly of the dendrimer- based nanoparticles and their interaction with si-RNA. “You can probably only do this sort of
research with a network of
people working together and within the context of this type of European project,” says Professor Catapano. Simplified funding and the convenience
of proximity are important factors, but above all Professor Catapano emphasises the quality of the research activity in the collaborating institutions. As the pace of activity in the field has picked up there are now a number of other groups also working on si-RNA anticancer treatments, as well as other polymers as potential delivery vehicles.
small interfering RNA inside the cells and minimise off-target toxicity. The focus of this project is prostate cancer
as the researchers have a wealth of experience in this type of cancer to build on. From this work however, they hope to generate a roadmap to transfer the knowledge to tackling other types of cancers. There are also a number of other projects
under way at the Institute of Oncology Research related to prostate cancer biology, transcription factors and epigenetic regulators, and building new mouse models of prostate cancer where new therapeutic approaches like the siRNA will be tested. Professor Catapano emphasises the
prominence at the centre of the translational research and early phase clinical studies,
Project Information AT A GLANCE
Project Title: DENANORNA: Dendrimers as nanovectors for targeted siRNA delivery in gene therapy (ERA-Net EuroNanoMedicine)
“The focus is prostate cancer as the researchers have a wealth of experience in this type of cancer... From this they hope to generate a roadmap to transfer the knowledge to tackling other types of cancers”
have
Professor Catapano and his already
colleagues demonstrated activity
inhibition using si-RNA in cell cultures in vitro as well as in mouse models. “What we have to do now is improve the second steps so we can really target specific cells.” This involves attaching molecules to specifically target tumour tissue. This should decrease toxicity as well as increasing the efficiency of the treatment. Other aspects for future work include improving the pharmokinetics and the selectivity, so that the nanoparticles are more readily taken up by the cancer cells. They are
also studying ways CONTACT
Carlo Catapano, MD, PhD He received his medical degree from the University of Naples, Italy, and the Ph.D. in Biochemistry from Wake Forest University (WFU) in Winston-Salem, NC, USA. He trained in medical oncology at the University of Naples, and in cancer pharmacology at the Mario Negri Institute for Pharmacological Research in Milan, Italy, and later in biochemistry and molecular biology at the WFU. He was on faculty at the Medical University of South Carolina (MUSC) in Charleston, SC, USA, from 1993 to 2003 in the Departments of Experimental Oncology, Medicine, Biochemistry and Molecular Biology, and
32
a senior investigator at the MUSC Hollings Cancer Center and the Center for Cancer Genomics. Since 2003 he is the Director of the Laboratory of Experimental Oncology of the Oncology Institute of Southern Switzerland (IOSI) and, since 2010, of the Institute of Oncology Research (IOR) in Bellinzona, Switzerland. He directs the Tumor Biology and Experimental Therapeutics Program.
Contact: Tel: +41 91 820 03 65 Email:
carlo.catapano@
ior.iosi.ch Web:
www.ior.iosi.ch
Insight Publishers | Projects Main Contact: to improve the efficiency of release of the
that is, the initial stages for using new drugs in human patients. “One of the things we are trying to do is to move things from the pre- clinical stage to the early clinical development phase,” he says. While this process is relatively rapid and straightforward with the small molecule drugs studied at the centre, transferring the project based around si-RNA molecules into clinical activity is still a good few years away. This is largely due to the complexity of the delivery system. Yet the main concept behind the approach is deceptively simple. And what is more beguiling still is the enormous promise of the progress so far.
Project Objective: The project combines complementary expertise in nanotechnology, molecular and cellular biology and biomedicine to exploit the potential of dendrimers as nanovectors for targeted delivery of small interfering RNA. Dendrimers conjugated with ligands or antibodies will be designed, tested by computer- aided modeling and assembled via chemical synthesis. Nanoparticle assembly, delivery of siRNA into target cells, and gene silencing efficiency will be investigated. In vivo validation of the siRNA-dendrimer delivery will be done in mouse models of human prostate cancer xenografts.
Project Duration and Timing: 3 years, January 2010 to June 3013
Project Funding: ERA-Net EuroNanoMedicine and Swiss National Foundation CHF 270’000.-
Project Partners: • Dr. Ling Peng CNRS, Marseille (UPR 3118 CINaM)
• Dr. Sabrina Pricl Trieste University • Dr. Angeles Munoz-Fernandez Hospital General Univesitario Gregorio Maranon /
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• Dr. Palma Rocchi INSERM • Dr. Valentin Cena Callejo NanoDrug S.L.
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