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Contexte
Effective cancer therapy still remains highly challenging tasks for both research and applications. Lack of tumor selectivity is the major limitation that inherent to most conventional anticancer chemotherapeutic agents. One-way to study selective drug targeting to tumors is to mimic the behavior of drug carriers in model tumor aberrant vascular architecture. Indeed due to their nanosize scale, intravenously administered drug carriers are unable to penetrate through tight endothelial junctions of normal blood vessels. They can however selectively extravagate into tumor tissues due to abnormal enhanced permeability of blood vessels in the vicinity of a tumor. Over time, due to lack of efficient lymphatic drainage, the drug concentration in tumor vicinity will build up reaching several folds higher than that of the plasma. These effects represent the enhanced permeability and retention (EPR) effect.
The delivery of nano-sized agents into cancer tissue is still problematic. It is believed that no more than 4% of injected nanoparticles could effectively reach the tumor due to the EPR effect. For this reason, EPR effect provides relatively modest specificity, about 20-30% increase in delivery, with carriers. However such increased efficiency has not yet been proven in human patients. The physics of nanocarriers trajectory through a network of micro-vessels of various sizes has been scarcely studied.
Projet
We believe that microfluidic technology offers unique possibilities to overcome this difficulty, by allowing to systematically studying vascular networks with setups that closely mimic the in vivo situation. In this project we are particularly interested in the behavior of fluorescent perfluorocarbon micro- or nano-droplets stabilized by fluorinated surfactants and dispersed in aqueous phases. Indeed, they represent promising candidates as contrast agents for 19F MRI, ultrasound imaging, and drug-carriers for targeted therapy. The flow of these particles and their permeation through the pores of model “veins” will be mainly studied under fluorescence microscopy. Several factors, expected to influence the extravasation, will be investigated.