| Centre
Paris-Saclay
| | | | | | | webmail : intra-extra| Accès VPN| Accès IST | English
Univ. Paris-Saclay

Sujet de stage / Master 2 Internship

Back to the internship list


Obtaining hybrid nanoparticles based on extracellular vesicles in microfluidics for heart disease therapy

Contact: GOBEAUX Frederic, , frederic.gobeaux@cea.fr, +33 1 69 08 24 74
Summary:
The aim of this Master 2 project is to develop a microfluidic approach to surface modification of extracellular vesicles, to make them stable and non-immunogenic when administered in vivo.
Possibility of continuation in PhD: Oui
Deadline for application:03/04/2024

Full description:
After cardiac ischemia, damaged myocardium can lead to heart failure. In recent years, the protective role of extracellular vesicles (EVs) in cardiac ischemia has been demonstrated in preclinical models(1). EVs, produced naturally by all cells, are very small particles (∼40-160nm) formed from a plasma membrane and containing nucleic acids and proteins(2). But limitations to their application in cardiac therapy exist, these being linked on the one hand to the limited quantities of EVs due to insufficient isolation yields and, on the other hand, to the cumbersome nature of conventional (micrometer-scale) EV production and isolation methods such as ultracentrifugation. Microfluidics has proven its worth for synthesizing monodisperse nanoparticles (NPs) by nanoprecipitation(3), but also for manufacturing more complex drug nanovectors such as Janus NPs(4,5). This strategy will be adapted to our project to achieve, through fine control of thickness, density, homogeneity and reproducibility of the process, a surface coating of EVs giving them properties of interest for therapeutic application.

The aim of this Master 2 project is to develop a microfluidic approach to surface modification of EVs, to make them stable and non-immunogenic when administered in vivo.
To achieve this, the student will have to :
- Obtain EVs from cultured cells, purify them (using dedicated kits) and characterize them (by Dynamic Light Scattering, Nanoparticle Tracking Analysis, CryoTEM, etc.).
- Optimize the parameters for using microfluidic chips and/or millifluidic mixers to obtain EVs embedded in a layer of either polymers or possibly modified lipids (already synthesized).
- In-depth characterization of post-coating EVs (size, cargo protein expression, stability, etc.) using methods already available at IGPS.

Internship context: The internship is funded by the HEALTHI interdisciplinary project at Université Paris Saclay. Work will take place at two sites: at the Institut Galien Paris Saclay (IGPS), UMR CNRS 8612, in the Henri Moissan research building (17 avenue des Sciences, 91 400 Orsay) for work on EVs production and characterization, and at the CEA- Saclay site (LIONS - NIMBE UMR 3685 CEA/CNRS) for work on microfluidics. Students will have access to state-of-the-art equipment at both sites, as well as to equipment on IPSIT (Ingénierie et Plateformes au Service de l'Innovation Thérapeutique) platforms.
Weekly meetings will be held to assess progress. In addition, oral presentations to the teams will take place during and at the end of the internship.

Contacts : Please send CV and covering letter to :
Prof. Myriam Taverna : myriam.taverna@universite-paris-saclay.fr and Dr. Frederic Gobeaux :
Frederic.GOBEAUX@cea.fr

References
1) Khan K. et al., Extracellular Vesicles as a Cell-free Therapy for Cardiac Repair: a Systematic Review and
Meta-analysis of Randomized Controlled Preclinical Trials in Animal Myocardial Infarction Models. Stem
Cell Reviews and Reports, 2022, 18(3):1143-1167, doi: 10.1007/s12015-021-10289-6
(2) Gandham S. et al. Technologies and Standardization in Research on Extracellular Vesicles, Trends in
Biotechnology, 2020, Volume 38, Issue 10, Pages 1066-1098, doi.org/10.1016/j.tibtech.2020.05.012
(3) Megan Havers, Axel Broman, Andreas Lenshof, Thomas Laurell - Advancement and obstacles in
microfuidics‑based isolation of extracellular vesicles, Analytical and Bioanalytical Chemistry (2023)
415, 1265-1285 - https://doi.org/10.1007/s00216-022-04362-3.
(4) Saqib M, et al., Microfluidic Methods in Janus Particle Synthesis, Int J Nanomedicine. 2022; 17:
4355–4366. doi: 10.2147/IJN.S371579.
(5) Zhang L. et al. Microfluidic Methods for Fabrication and Engineering of Nanoparticle Drug Delivery
Systems, ACS Appl. Bio Mater. 2020, 3, 1, 107–120 doi :10.1021/acsabm.9b00853.
Technics/methods used during the internship:
- microfluidics & millifluidic mixers - EV and coated EV characterization: Dynamic Light Scattering, Nanoparticle Tracking Analysis, CryoTEM, etc.

Laboratory
Tutor of the internship
Other related link

 

Retour en haut