|
|
Biography |
|
|
Pr Patrick COUVREUR is Full Professor of Pharmacy at the Paris-Sud University and holder of the chair of “Innovation Technologique” (2009-2010) at the prestigious « Collège de France ». He was recently appointed as a Senior Member of the “Institut Universitaire de France”. He is the recipient of an “ERC Advanced Grant” (2010-2015).
Pr Patrick COUVREUR’s contributions in the field of drug delivery and targeting are highly recognized around the world through 430 research articles, 250 invited lectures, 59 patents and the main author/editor of 7 books (H-index 66 and 14,000 citations) . His research is interdisciplinary and focuses on the conception of nanomedicines for the treatment of severe diseases (cancer, infectious diseases and neurological disorders). Methodologies are at the interface between Physico-Chemistry of Colloids, Polymer Chemistry, Material Science and Pharmacology/Cancerology.
Patrick COUVREUR’s research has led to the funding of two start-up companies (Bioalliance, 70 employees and Medsqual). The major scientific contribution of Patrick COUVREUR to the Pharmaceutical Sciences is also recognized by numerous international awards among which, the «1990 Young Investigator Award for Excellence in Research» of the «Controlled Release Society» (USA), the «Pharmaceutical Scientist of the Year 1996 Award» of the International Federation of Pharmacy (FIP), the “2004 Pharmaceutical Sciences World Congress Award” (Kyoto, Japon), the prestigious “Host Madsen Medal” (Beijin, 2007), the “Marie-Maurice Janot Award Lecture” (2008), the Prix Galien 2009 and the European Pharmaceutical Scientist Award 2011. His appointment as a member of four academies (Académie des Technologies, Académie de Médecine and Académie de Pharmacie in France as well as Académie Royale de Médecine in Belgium) is another recognition of major scientific and scholarly contributions of Patrick COUVREUR.
|
|
|
|
|
|
|
Abstract |
|
|
|
|
NANOMEDICINE FOR CANCER TREATMENT AND THERAGNOSTIC |
|
|
|
|
|
Even if new molecules are discovered to treat cancer diseases, the clinical use and efficacy of conventional chemotherapeutics is hampered by the following limitations : i) drug resistance at the tumor level due to physiological barriers (non cellular based mechanisms) ii) drug resistance at the cellular level (cellular mechanisms), and iii) non specific distribution, biotransformation and rapid clearance of anticancer drugs in the body. It is therefore of importance to develop nanodevices able to overcome resistance of cancer cells or tissues to chemotherapeutic treatments.
This is illustrated by the camouflage of doxorubicin into polyalkylcyanoacrylate nanoparticles, allowing to overflow the PgP detoxification capacity, thus inducing reversion of the multidrug resistance (MDR). The higher cytotoxicity of doxorubicin when loaded onto poly(isohexylcyanoacrylate) nanoparticles has been shown on the X/myc transgenic mouse model of hepatocellular carcinoma which mimics several steps of human hepatocarcinogenesis (Barraud, et al., J. Hepathology, 42, 736-743; 2005). Based on these data, a phase III multicentric clinical trial is currently performed on patients with resistant hepatocarcinoma or liver metastasis.
Another illustration of this approach is the squalenoylation (Couvreur et al., Nano Letters, 6, 2544-2548; 2006), a technology that takes advantage of squalene's dynamically folded conformation to link this natural lipid to anticancer and antiviral nucleoside analogues in order to achieve the spontaneous formation of nanoassemblies (100–300 nm) in water without the aid of surfactants (Couvreur et al., Small, 4, 247-253; 2008). When applied to the anti-cancer compound gemcitabine (Harivardhan Reddy et al., Mol. Pharm.,6, 1526-1535; 2009), this original concept was demonstrated to be able to overcome different mechanisms of resistance to gemcitabine (Harivardahan Reddy et al., J. Pharmacol. Exp. Ther., 325, 484-490; 2008) , ie. deamination of gemcitabine by the blood deaminases, down regulation of nucleoside transporters (Bildstein L et al., J Control Rel, 147,163-170; 2010) and/or insufficient phosphorylation by the deoxycytidinekinases (dCK). Indeed, the squalenoylated gemcitabine nanoparticles were found (i) to be resistant to deaminases, (ii) to diffuse intracellularly independently of the presence of nucleoside transporters and (iii) to improve the phosphorylation of gemcitabin by dCK. This breakthrough concept has been further enlarged to other anticancer drugs, including paclitaxel (Dosio et al., Bioconjugate Chem. 21, 1349–1361; 2010), cisplatin and small interfering RNA for the inhibition of the ret/PTC fusion oncogene in the papillary thyroid carcinoma (Raouane et al., J. Med. Chem., 54, 4067–4076; 2011). The entrapment of ultrasmall iron oxide nanoparticles in those squalene-based nanoassemblies has further allowed to design multifunctional nanoparticles combining therapeutic and imaging properties (ie. the so-called “nanotheragnostics”) (Arias et al., ACS Nano, 22, 1513-1521; 2011). This new concept opens the way to the personalized medicine .
Finally, the use of nanohybrids (Horcajada et al., Nature Materials, 9, 172-178; 2010) constructed with metal organic frameworks (nanoMOFs) will be reviewed for their ability to encapsulate unprecedent high quantities of the anticancer compound busulfan (Mc Kinlay et al., Angew Chem Int Ed Engl. , 23, 6260-6266; 2010).
Acknowledgements: part of this presentation benefits from the financial support of the European Council under the ERC Advanced Grant n°249835 “TERNANOMED”
|
|
|
|
|