Sujet de stage / Master 2 Internship

The aim of this internship is dedicated to the synthesis of functionalized lipid-polymer nanoparticles by microfluidics.

Context:
Retinoblastoma (Rb) is a cancer of the retina that affects 1 in 15 to 20000 births each year. Conventional treatments include enucleation and chemotherapy. For small solid tumors like Rb, photodynamic therapy (PDT) may be of benefit because it is non-mutilating and generates few side effects. Phototoxicity results from the combination of effects of a photosensitizer (PS), light and oxygen. In such a context, the design of a functionalized colloidal nanocarrier which could solubilize, protect and lead porphyrin (PS) derivatives towards their target cells, facilitate their penetration and release in cell cytoplasm before illumination, would optimize the therapeutic effect. The final aim of the project LPHN-OnAChip is to form and functionalize in a single microfluidic chip hybrid nanoparticles (lipid-polymer nanoparticles referred as LPHN) co-encapsulating an anti-cancer drug and a photosensitizer associated to ligands. The rationale for co-encapsulating the anticancer drug is to overcome the lower efficacy of PDT in hypoxic areas of the tumor. The project is based on complimentary expertise of two laboratories in innovative drug delivery systems, physico-chemical and biological evaluation of targeting of porphyrins for PDT (IGPS) and in the self-assembling systems, in situ characterization and microfluidics (LIONS).

Mission:
The aim of this internship is dedicated to the synthesis of functionalized LPHNs by microfluidics. First, the student will become familiar with the formation of polymer nanoparticles (poly(lactic acid) NPs) and vesicles by microfluidics by reproducing the protocols established by previous works in the laboratory. Then, he or she will study the feasibility of forming vesicles incorporating a porphyrin (porphyrin-glutaric acid) for further functionalization. By playing on hydrodynamic parameters and on the initial concentration, porphyrin loading will be studied. If necessary different phospholipids will be tested. The obtained vesicles will be characterized by several technics available in the consortium.
In a second step, the candidate will investigate the formation of LPHNs by coating the previously obtained poly(lactic acid) NPs with liposomes carrying PS.
Several characterization technics will be used such as Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), epifluorescence microscopy, confocal microscopy, Cryo-Transmission Electron Microscopy (Cryo-TEM).

Profile:
We are looking for applicants having a background such as Engineering/Physico-chemistry/Chemistry, skills in microfluidics will be an asset but it is not mandatory. The applicant must be highly motivated by tackling challenges of working with multidisciplinary teams.
Applicants will have an experimentalist profile.
Applicants shall speak English or French, and have good communication skills.

Duration: 6 months
Starting date: To be filled first trimester 2023
Localization: LIONS at CEA/Saclay, Gif sur Yvette France
Contacts CV, motivation letter and recommendation letter should be sent to all contacts:
Dr. Florent Malloggi : florent.malloggi@cea.fr
Dr Patrick Guenoun : patrick.guenoun@cea.fr
Prof. Véronique Rosilio : veronique.rosilio@universite-paris-saclay.fr