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par Emilie Secret - 19 avril

Nanoparticles usually enter cells by endocytosis and are trapped in intracellular vesicles called endosomes (fig 1 right). The bypass of the endocytosis pathway is a major challenge in cell engineering, for the delivery of active molecules or for the targeting of organelles. [1,2] This PhD project will focus on the development of a new generation of magnetic liposomes which are able to fuse with membranes (Figure 1, left). [3,4] The objective is to deliver magnetic nanoparticles directly into the cytosol and to avoid the endosomal trapping. In the particular case of magnetic nanoparticles, the challenge is also to restore their heating properties under an alternative magnetic field and the possibility to manipulate them with a magnetic field gradient. The project will focus on the synthesis of fusogenic magnetic liposomes and their interaction with model membranes (giant vesicles) and cells.

Figure 1 : left) Fusion of fusogenic liposomes with cell membrane and delivery of nanoparticles in the cytosol ; right) Endocytosis of standard liposome and trapping of the nanoparticles in endosomes.

Profile : Candidates must hold a master’s degree in chemistry, physical chemistry or a master’s degree in chemistry for health. Research experience at the chemistry-biology interface will be appreciated.

References :
[1] S. Du, S. S. Liew, L. Li, S. Q. Yao, Bypassing Endocytosis : Direct Cytosolic Delivery of Proteins, J. Am. Chem. Soc, 2018, 140, 15986-15996.
[2] M. Le Jeune, E. Secret, M. Trichet, A. Michel, D. Ravault, F. Illien, J-M Siaugue, S. Sagan, F. Burlina, C. Ménager. Conjugation of Oligo-His Peptides to Magnetic γ-Fe2O3@SiO2 Core–Shell Nanoparticles Promotes Their Access to the Cytosol. ACS Appl. Mater. Interfaces 2022, 14, 13, 15021–15034.
[3] S. Kube, N. Hersch, E. Naumovska, T. Gensch, J. Hendriks, A. Franzen, L. Landvogt, J.P. Siebrasse, U. Kubitscheck, B. Hoffmann, R. Merkel, A. Csisza, Fusogenic Liposomes as Nanocarriers for the Delivery of Intracellular Proteins, Langmuir 2017, 33, 1051, 8722 ;10593.
[4] F. Chen, M. Bian, M. Nahmou, D. Myung, J. L. Goldberg, Fusogenic liposome-enhanced cytosolic delivery of magnetic nanoparticles, RSC Adv, 2021, 11, 35796-35805.

Location : Sorbonne Université , PHENIX Laboratory, Paris, France.
Beginning of the PhD : 01/10/2022

Contact : Christine Ménager,

Plus de details et candidature :