Dr. Nicolas TAULIER

Theranostic nanosystems

Introduction

Medecine is moving towards a personalized therapy, that requires the development of adapted tools able to reduce the undesirable side effects of drugs while increasing their effectiveness.

In this context, I am studying new intravenously injectable theranostic agents. Their role is to allow an visualization of cancer tumors combined with a localized and controlled administration of drugs.

After injection, these theranostic agents are filtered by different organs: mainly the liver and the spleen for agents with a diameter larger than 200 nm, and by kidneys for agents smaller than 50 nm. If these organs are not those targeted by the theranostic agents, then they should possess a diameter D within the range 50 < D < 200 nm in order to freely circulate into the bloodstream and reach the targeted organ. Targeting will be carried out thanks to molecules disposed on the agent surface that will specifically bind a specific receptors of the targeted tissue.

Echography and magnetic resonance imaging (MRI) imaging methods are ideally suited to the use of contrast agents. Ultrasound has a real-time imaging capability, it is a cheap technology and is available in most hospitals. While MRI provides the best spatial resolution, but is expensive and of low availability. Commercial contrast agents available for both techniques are not suitable for theranostic applications. Indeed, commercial ultrasound contrast agents are micrometric bubbles (1 - 12 microns in diameter) that dissolve quickly in the vascular network, which represents a significant barrier to their use as quantitative markers or drug carriers. To the contrary, commercial MRI contrast agents are very small molecules, usually made of gadolinium, that leak easily through the wall of healthy vessels and get rapidly dispersed in all tissues.

It is possible to overcome the limitations of both imaging modalities using perfluorocarbon (PFC) nanodroplets as contrast agents. Indeed, these droplets can be detected by fluorine MRI (19F MRI). If however these nanodroplets represent inefficient ultrasound contrast agents it is possible to significantly improve their echogenicity by vaporising the droplet so that they become microbubbles. However, the use of perfluorocarbon nanodroplets as theranostic agent faces two major challenges: the production of stable droplets and encapsulation of drugs. These two difficulties are related to the fact that perfluorocarbons have little or no affinity for molecules that do not contain fluorine atoms.

My current research goals are to obtain nanoparticles that can be used efficiency as constrat agents (either for ultrasound, MRI or other imaging techniques) but also as drug carriers. In the latter case, I focus my work on a controlled and localized release of drugs that will be triggered by focused ultrasound wave. Whatever the targeted organ, a non-negligible amount of nanoparticles will not accumulate on the site to be treated. To fully reduce drug side effects, I also propose to use drugs which are themselves activated by ultrasound. In the absence of ultrasound, these drugs are therefore harmless.

Nanoparticles under study

We are studying nanoparticles composed of a perfluorocarbon liquid core encapsulated inside a shell. As shell materials, we used either:

We are characterizing numerous properties of these nanoparticles when in suspension. Among these properties are

We are also investigated the properties of fluorinated surfacants such as

These measurements help us to validate analytical and numerical models we are developing as well as to understand the relationship between the nanoparticles properties and their behavior.

Theranostic properties

We are evaluating the capacity of these nanoparticles to be good contrast agents as well as the use of ultrasound to deliver drug encapsulated inside these nanoparticles.

Modeling the interaction ultrasound-nanoparticles

We are developing simulations and analytical models in order to predict the behavior of these nanoparticles under an acoustic fields. In particular we wish to predict the following properties

based on the physical and chemical knwoledge of the nanoparticle properties.

Related funding

Related publications