dynamic functionalisation of large pore mesoporous silica

6-MONTH INTERNSHIP OFFER
Montpellier
FRANCE
DYNAMIC FUNCTIONALISATION OF LARGE PORE
MESOPOROUS SILICA NANOPARTICLES WITH
AMINO ACIDS FOR THE EFFICIENT
COMPLEXATION OF NUCLEIC ACIDS
BACKGROUND. The first partner (J.O. Durand, Laurence Raehm, Clarence Charnay, ICGM) has an expertise in the
design, preparation, and characterization of materials derived from Mesoporous Silica Nanoparticles (MSN) for
health applications.[1] For instance, we recently reported several multifunctional Mesoporous Silica
Nanoparticles – containing photosensitizers, targeting groups, and fluorescent reporters – for targeted
photodynamic therapy,[2] and gene delivery applications.[3]
TEM Picture of MSN
The second partner (S. Ulrich, IBMM) has an expertise on the generation of adaptive biomaterials using dynamic
covalent chemistry. For instance, we recently reported the generation of multivalent peptide-based cationic
clusters that are self-assembled in situ through multiple acylhydrazone ligations,[4] and of pH-sensitive dynamic
covalent polymers[5] that are both capable of effectively complexing nucleic acids (DNA, siRNA) through
multivalent interactions.[6]
Project. The aim of the project is to combine the expertise of both partners in order to generate functional
mesoporous Silica Nanoparticles (MSN)s for nucleic acid recognition and delivery. We will use dynamic covalent
chemistry as a dynamic functionalization approach in order to modify post-synthetically these materials. This
proposed implementation of a dynamic approach represents a significant step towards adaptive materials which
synthesis by post-functionalization is guided by and optimized for the pDNA target, and which show
responsiveness to chemical stimuli.
The applicant will have to synthesize large pore MSN functionalized with aldehyde groups in the pores following
the procedure described with silica.[7] The applicant will then have to perform the synthesis of hydrazides-based
cationic amino acids (lysine, histidine, arginine), and to dynamically couple them in the pores. The unique
advantage provided by the reversibility of the ligation reaction is to make these materials dynamic so that they
can adapt to environmental conditions such as the presence of the biological target. Therefore, we will focus on
evidencing template effects whereby the pDNA target guide the post-functionalization of the pores by selecting
the appropriate binding groups that favor the formation of the best binding pores. Different pore size will be
studied as this parameter can greatly influence the binding of pDNA. The applicant will use agarose gel
electrophoresis to characterize the pDNA complexation.
FUNDING. This project has been selected for funding by the Laboratory of Excellence (LabEx) CheMISyst. Stipend
will be around 500€ monthly. Internship can start in January or February 2017.
CANDIDATE. We are looking for a final year Master student (M2, Ingénieur) with a keen interest for the interface
of organic, material and bioorganic chemistry. The project will involve organic synthesis as well as nanoparticle
formation by sol-gel processes, characterization techniques (NMR, UV-Vis), and some biochemical experiments
(gel electrophoresis).
CONTACTS: send CV and cover letter to Dr. Jean-Olivier Durand ([email protected]), Dr. Sébastien Ulrich
([email protected])
References.
[1] a) A. Chaix, K. El Cheikh, E. Bouffard, M. Maynadier, D. Aggad, V. Stojanovic, N. Knezevic, M. Garcia, P. Maillard, A. Morere, M. GaryBobo, L. Raehm, S. Richeter, J. O. Durand, F. Cunin, J. Mat. Chem. B., 2016, 4, 3639-3642; b) H. Alhmoud, B. Delalat, R. Elnathan, A.
Cifuentes-Rius, A. Chaix, M. L. Rogers, J. O. Durand, N. H. Voelcker, Adv. Funct. Mat., 2015, 25, 1137-1145.
[2] a) J. G. Croissant, S. Picard, D. Aggad, M. Klausen, C. M. Jimenez, M. Maynadier, O. Mongin, G. Clermont, E. Genin, X. Cattoen, M. W.
C. Man, L. Raehm, M. Garcia, M. Gary-Bobo, M. Blanchard-Desce, J. O. Durand, J. Mat. Chem. B., 2016, 4, 5567-5574; b) J. G.
Croissant, C. Mauriello-Jimenez, M. Maynadier, X. Cattoen, M. W. C. Man, L. Raehm, O. Mongin, M. Blanchard-Desce, M. Garcia, M.
Gary-Bobo, P. Maillard, J. O. Durand, Chem. Commun., 2015, 51, 12324-12327; c) C. Mauriello-Jimenez, J. Croissant, M. Maynadier, X.
Cattoen, M. W. C. Man, J. Vergnaud, V. Chaleix, V. Sol, M. Garcia, M. Gary-Bobo, L. Raehm, J. O. Durand, J. Mat. Chem. B, 2015, 3,
3681-3684; d) M. Gary-Bobo, Y. Mir, C. Rouxel, D. Brevet, I. Basile, M. Maynadier, O. Vaillant, O. Mongin, M. Blanchard-Desce, A.
Morere, M. Garcia, J. O. Durand, L. Raehm, Angew. Chem. Int. Ed., 2011, 50, 11425-11429; e) P. Couleaud, V. Morosini, C. Frochot, S.
Richeter, L. Raehm, J. O. Durand, Nanoscale, 2010, 2, 1083-1095; f) D. Brevet, M. Gary-Bobo, L. Raehm, S. Richeter, O. Hocine, K.
Amro, B. Loock, P. Couleaud, C. Frochot, A. Morere, P. Maillard, M. Garcia, J. O. Durand, Chem. Commun., 2009, 1475-1477.
[3] D. Brevet, O. Hocine, A. Delalande, L. Raehm, C. Charnay, P. Midoux, J. O. Durand, C. Pichon, Int. J. Pharm., 2014, 471, 197-205.
[4] a) E. Bartolami, Y. Bessin, V. Gervais, P. Dumy, S. Ulrich, Angew. Chem. Int. Ed., 2015, 54, 10183-10187; b) E. Bartolami, Y. Bessin, N.
Bettache, M. Gary-Bobo, M. Garcia, P. Dumy, S. Ulrich, Org. Biomol. Chem., 2015, 13, 9427-9438.
[5] C. Bouillon, D. Paolantoni, J. C. Rote, Y. Bessin, L. W. Peterson, P. Dumy, S. Ulrich, Chem. Eur. J., 2014, 20, 14705-14714.
[6] E. Bartolami, C. Bouillon, P. Dumy, S. Ulrich, Chem. Commun., 2016, 52, 4257-4273.
[7] S. Kar, P. Joly, M. Granier, O. Melnyk, J. O. Durand, Eur. J. Org. Chem., 2003, 4132-4139.