ZAWACKA PROGRAMME – Dr. Mathilde Ponchelle
Zawacka NAWA - exchange programme for students and scientists as part of bilateral cooperation – inbound offer 2023-24
Ms Mathilde Ponchelle from Commissariat de l'énergie atomique et des énergies alternatives (CEA) Saclay / Université de Paris Saclay received six months scholarship to perform studies to her doctorate at the Centre of Excellence NOMATEN.
Title of the project: Design and synthesis of fluorinated micelles encapsulating gold nanoparticles for radiotherapy
Abstract – research plan: Over the past few years, medicine has been a field in which nanotechnologies have shown great promise particularly for diagnosis and drug-delivery applications. The challenge of nanomedicine consists in carrying active molecules through the different biological barriers and reaching specific targets in an efficient and nontoxic way. In addition, some active agents require specific formulations to overcome intrinsic problems associated with aqueous insolubility, in vivo stability, and bioavailability.
With the advent of nanotechnologies, a whole range of new carriers with different properties and functionalities are now available. However, the development of small biocompatible carriers with high loading capacity, extended circulation time and favourable biodistribution has several unanswered issues. Examples of nanometric delivery systems that are currently applied or under development include polymers, liposomes, lipidic nanoparticles, dendrimers, carbon nanotubes, metallic nanoparticles, and micelles. Micelles are made of amphiphilic molecules consisting of two distinct regions with opposite affinities towards a given solvent (for example, water). They self-assemble as colloidal particles with a hydrophobic core and hydrophilic shell. When used as aqueous carriers, micelles can efficiently solubilize pharmaceuticals in their core.
The objective of this PhD project is to design nanometric platforms based on gold nanoparticles encapsulated in fluorinated micelles. Micelles will be designed in such a way that they become biocompatible and can passively reach the tumour area thanks to local leaky vasculature (EPR effect). Contribution of gold is essential as sensitizer for radiotherapy. In fact, gold can potentiate radiotherapeutic treatments by producing altering species upon irradiation. We thus anticipate better efficacy of radiotherapy. In addition, tumour tissues are often hypoxic tissues, which poorly respond to radiotherapeutic interventions. The fluorinated core of the micelle will contribute favourably to the latter point as fluorinated phases have the ability to dissolve and carry molecular oxygen. Encapsulation of oxygen close to the reactive metallic core (gold) will allow the production of altering reactive oxygen species, upon irradiation. This phenomenon will contribute to the eradication of the cancer tissues.
