Post-doctoral proposal Title: mechanical and acoustical modeling of NAnometric Biocapsules for Ultrasonic triggering of anti-Cancer veCtOrized drug delivery (NABUCCO)
Description A nanometric Ultrasound Contrast Agent (nUCA) is a new type of contrast agents currently investigated for nanomedicine applications, especially targeted drug delivery monitored by ultrasound. In the treatment of cancer, targeted chemotherapy would reduce both severe side effects and cell resistance and therefore provide substantial benefits. nUCAs have to be multifunctional particles. They have to satisfy the following properties: 1) be of nanometric size (diameters < 400 nm) to extravasate through the gaps between the endothelial cells of the anomalous vascularization of the tumor; 2) have a sufficient lifetime after intravenous administration to sustain pressure and mechanical stress and accumulate within the tumor to deliver sufficient quantities of drug; 3) be biocompatible and biodegradable; 4) afford drug encapsulation; 5) be sufficiently echogenic, at low ultrasonic levels, to be used as contrast agents so that their proper accumulation at the tumor location can be monitored; 6) be able to deliver drug at higher ultrasound levels should, either by particle shell breaking or vaporization. Points 1) to 4) deal with the chemical design and manufacturing of nUCAs which is partially realized at the present stage. Points 5) and 6) deal with the physical interaction of nUCAs with an ultrasound field, which is the objective of the proposal. The advanced modeling of this interaction is required in order to: - identify in a quantitative way the mechanisms of ultrasound interactions with nUCAs, - define the mechanical / physical requirements for an opimized design of nUCAs. This will be accomplished by the post-doc through 3 main tasks she/he will take part to: - Task 1 : update of an existing theoretical model1 on the interaction between ultrasound and nUCAs. - Task 2 : validate this model by comparison with in vitro measurements of ultrasound propagation in suspensions of nUCAs, either transmission or back-scattering measurements - Task 3 : update an existing numerical model to include the theoretical model developed in task 1.
Duration : 18 months, starting date ideally March or April 2013 Funding : project "NABUCCO", PLAN CANCER, INSERM, selected June 2012, starting date : 1st December 2012 Contact : François Coulouvrat, Institut Jean Le Rond d'Alembert, UMR CNRS 7190, Université Pierre et Marie Curie, 4 place Jussieu, 75252 Paris cedex 05, France –
[email protected] (please join a CV and a motivation letter)
1
F. Coulouvrat , J.-L. Thomas, K. Astafyeva, N. Taulier, J.-M. Conoir, W. Urbach, “A model for ultrasound absorption and dispersion in dilute suspensions of nanometric contrast agents”, J. Acoust. Soc. Am., accepted, in the press
