Novel lipid nanocapsules of anti alpha 1 sodium pump subunit siRNA to specifically target metastatic melanomas
Organization: Université d'Angers
Location: ANGERS Cedex, France
Field: Medical sciences
Requirements:
- EU citizen who has not spent more than 12 months in France within the last three years
- PhD (obtained BEFORE the application) in pharmaceutical sciences, biology or biochemistry
- Ideally (not mandatory) applying for a second/third post-doc fellow
Abstract:
Post-doctoral fellow supported by a mobility Marie Curie (People FP7) Grant on Novel lipid nanocapsules of anti alpha 1 sodium pump subunit siRNA to specifically target metastatic melanomas
Description:
Melanomas are highly aggressive tumors associated with very dismal prognosis as soon as they have metastasized. Despite significant efforts to develop adjuvant therapies, the best response rate with the standard FDA-approved treatment dacarbazine is as low as 16%. These highly disappointing statistics are likely related to the intrinsic resistance of melanoma cells to apoptosis. We evidenced the up-regulated expression of sodium pump 1 in ~20% of human primary melanomas in correlation with the Breslow index which still remains the best prognosis indicator to date. In addition, 30% of melanoma metastases (lymph nodes or subcutaneous) over-express 1 subunits, a result which reached 72% in the case of brain metastases. Our previous data revealing that inhibition of sodium pump subunits’ activity by means of cardenolides markedly impairs cancer cell migration and kills apoptosis-resistant cancer cells, may afford a therapeutic opportunity. These compounds unfortunately target the various alpha sodium pump subunits leading to possible secondary non selective effects. Indeed, numerous publications have shown that the therapeutic window of such compounds is generally very narrow. Therefore, a specific α1 targeting approach in human melanoma cells by means of siRNA has been developed with success in vitro. Gene expression silencing approaches are now widely developed for anti-cancer treatment purposes as assessed by the increasing number of clinical trials.
The purpose of this project is to develop lipid nanocapsules of lipoplexed anti-1 siRNA to be delivered in vivo. Specific cancer cell targeting should be achieved by i) passive enhanced permeability retention phenomenon due to the composition, size and stealth properties of the nanocapsules and ii) active targeting by coupling with various antibodies.
The applicant will prepare different nanocapsule types, evaluate their physico-chemical properties, their half-life in blood, their accumulation in the tumor models and their therapeutic benefits.
Contacts: Professor Catherine Passirani
e-mail: catherine.passirani@univ-angers.fr
phone: 00 33 (0)2 44 68 85 34
Deadline: 20-06-2011
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