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Dynamic Libraries for the Synthesis of New Multifunctional Silica Striped Nanoparticles

Final Report Summary - TRANSFORMERSURFACES (Dynamic Libraries for the Synthesis of New Multifunctional Silica Striped Nanoparticles)

TransformerSurface is a project that aims to optimize a new way to synthetize cheap and biocompatible nanoparticles functionalized taking account on the principles of the Dynamic Combinatorial Chemistryref. The goal is to obtain a new surface suitable for a larger range of possible functionalization. In particular, taking inspiration from the striped gold nanoparticles have been recently discovered in the group,ref this project is targeted to functionalize the outermost coating of the silica nanoparticles with higher order patterns, such as patches or stripes. A particular type of gold NPs surface assembly with a heterogenous, ordered ligand shell has the ability to diffuse through cell membranes, making it an excellent candidate for drug delivery. In fact, these ‘striped’ nanoparticles are capable of penetrating cell membranes without porating (creating transient holes associated with leakage and cytotoxicity) as viruses do.
As it is specified on the planning and the work packages, the first main objective of the project was to optimize a “new” surface on silica nanoparticles characterized by a functionalization that can be further modified. For doing this we choose a set of Dynamic combinatorial librariesref i.e. a group of molecules able to form, in our specific case, imminic bonds,ref which can be later hydrolyzed changing the environmental conditions. We decided to choose this approach because of two main reasons. The first reason regard the fact that one of the main research field developed in the group regard the functionalization of mixed ligand gold nanoparticles where the ligand can arrange in different ways (patches, janus, stripes) depending on the size of the core and the nature of the ligands.ref Of course the use of silica instead of gold would reduce the cost of the synthesis; moreover it is known that silica has no intrinsic photochemical properties and it is transparent. This is very important in case of functionalization or doping with fluorescent molecules that are very used in case of biological application. Finally and more importantly, we can in this way reduce the toxicity of the particles, in fact silica is well known to be high inert, hence biocompatible.
The overall work has been carried out at the SUNMIL laboratory at the École Polytechnique Fédérale de Lausanne (EPFL) under the supervision of Professor Francesco Stellacci who has a decennial experience on study of self-assembled monolayers (SAMs) on flat surfaces and nanoparticles.
We planned the main work package of the project to have the same duration of the project itself as it is focused on finding libraries suitable for our purposes. In fact one of the key components of this project is the synthesis of a series of dynamic libraries and the study of their reversibility. Specifically the plan was to take advantage of the principles of the Dynamic Combinatorial Chemistry that rests on the design and the synthesis of libraries of species connected by reversible (supra)-molecular bonds. Based on data already reported in literature and experimental analysis, we decide to focus on a limited number of libraries for the first period, which all have in common the possibility to form a reversible iminic bond
In the first period we focused our attention to the study of a range of dynamic libraries starting from the data reported in literature. After confirming the interaction between the molecules and the reversibility of the imminic bond, we proceed with the synthesis of silica nanoparticles functionalized using the same principles.
Functionalized particles were analyzed by NMR, TGA and IR spectroscopy. Once known that nanoparticles are clean and well functionalized we moved our attention on the arrangement. Unfortunately in this case the techniques normally used to characterize the morphology of the self-assembled monolayers (SAMs) on gold particles are not so straightforward and very challenging. After excluding STM due to the fact that silica particles are not conductive, we decided to use AFM with very good results.
Considering the extensive work done by the group and the fellow on the characterization of SAMs on gold nanoparticles using SANS, the same measurements have been performed on silica NPs.
Measurements in this case also are very promising and they just need to be more refined. It is important to know that for this experiment we obtained a 5 days beam time at FRMII in Munich.
Another approach was used to try to understand the possible formation of patches on the surface of our silica nanoparticles. By using a second layer of molecules having a coordinating group on the outside, we tried to grow gold particles on our silica particles in case of we had thiol terminated ligands, or covalently bind already synthetized acid functionalized gold particles in case on amino terminated silica. The experiments showed quite nice results although the binding might be sometimes aspecific.
Finally, quantification measurements of the ligand on the surface of the nanoparticles have been carried out by using NMR. In particular, taking advantage of our use of dynamic combinatorial chemistry for the functionalization of our silica nanoparticles and of the reversible nature of the imminic bond, we performed the hydrolysis of the double bold in order to recover the ligands attached and verify the presence of the used molecules on the surface.
In general a very extensive work has been carried out for the understanding of the chemical composition and the morphology of the surfaces of silica nanoparticles. Overall the project has showed many difficulties that the fellow has solved using different techniques and her expertise. As the project was going on we decided to focus our attention on the synthetic part and especially on understanding the mechanism and the conditions of assembly of the molecules on the surfaces. Understanding the chemistry is in fact a crucial aspect to solve before going into any biological experiments so we tried to make the synthesis and the experiments as well as the interpretation of the date more clear and clean in order to avoid mistake and mis-interpretations. Due to this only few biological experiments have been tried that for now didn’t show significant results in correlation with the arrangement of the ligand on the surface. We believe anyway that the system thought in this way is very promising.
The results obtained were biweekly presented to the SUNMIL group. In the optic of starting the biological experiments the results obtained on the synthesis of the nanoparticles were discussed with our partner group at Campus IFOM-IEO in Milan. The results were also presented at several conferences and meetings.
The fellow also participated to assess the scientific progress of the fellowships and also to take the opportunity to discuss in general on the PEOPLE program and H2020, administrative aspects, career development issues, integration of the fellow in the host country, communication with REA and the European Commission, benefits of the Marie Curie Actions to the host institution etc.
She collaborated extensively to the two following papers: “Determination of monolayer-protected gold nanoparticle ligand–shell morphology using NMR” Xiang Liu, Miao Yu, Hyewon Kim, Marta Mameli & Francesco Stellacci, Nature Communications 3, Article number: 1182; “Scanning tunneling microscopy and small angle neutron scattering study of mixed monolayer protected gold nanoparticles in organic solvents” Mauro Moglianetti, Quy Khac Ong, Javier Reguera, Kellen M. Harkness, Marta Mameli, Aurel Radulescu, Joachim Kohlbrecher, Corinne Jud, Dmitri I. Svergun and Francesco Stellacci, Chem. Sci., 2014,5, 1232-1240. Especially the experiments performed in different outstanding facilities as PSI, ILL, FRMII for the realization of the second paper contributed to the high formation of the fellow who was then able to perform experiments independently.
She contributed to the formation of many students and in general to the organization and the management of the host laboratory, including being responsible for the safety.
The fellow attended several seminar organized by the Institute des Materioux in Lausanne.