Multifunctional Silica nanoparticles with complex architecture based on metal atom cluster with potential application in biotechnologies – CLUSTOP

In this project the new X@SiO2 nanoparticles were synthesized by microemulsion process by using up-conversion nanocrystal and /or transition metal atom clusters synthesized by solid state chemistry [Clusters = [M6X14]n- (M = Mo, Re; X = S, OH, Cl, Br, I; n = 2, 4)]. Those nanoparticles are mainly based in a silica matrix controlled in size (> 50 nm). The silica matrix has been chosen because it is transparent in the NIR field, biocompatible, easily functionalizable and it offers numerous potential applications. Moreover, from optical point of view, clusters compounds are phosphorescent with high quantum yield and life time, so they gather the two assets of the molecular and inorganic phosphors: the nanometric size of organic dyes and the photobleaching resistance of QDs. Indeed [M6X14]2- units are currently the smallest inorganic nanometric entity resistant to photobleaching and free of toxic elements, which emit in the NIR field. Moreover, as part of the risk evaluation before potential applications of nanomaterials, we have analyzed the impact on animal and plant cells of newly designed multifunctional silica nanoparticles with complex architecture and with potential application in biotechnologies.

Considering this context, the CLUSTOP project have consisted to elaborate new non-toxic, magnetic and NIR-emitting phosphorescent silica nanoparticles, and studied their physicochemical and toxicological properties. Separately, a lot of effort were done to improve the quantum yield of metal atom clusters. This purpose, “up-conversion” nanocrystals (ß-Na(Y,Gd)F4:Yb:Tm) were introduced along with clusters into silica particles in order to obtain silica particles that will be photo-excitated in the NIR and able to emit in the same region (noted ß-NaGdF4:Yb:Tm@NaGdF4-Cs2Mo6X14@SiO2). In parallel, ?-Fe2O3 were introduced along with cluster into silica particles (noted ?-Fe2O3-Cs2Mo6X14@SiO2) in order to obtain superparamagnetic properties in combination with luminescence.
We showed that X@SiO2 nanoparticles have low effect on cell growth or viability but this effect is highly depending of the cellular-type. In parallel, we proved that these nanoparticles can be easily internalized by cancer cells after surface functionalization by transferrin protein and imaged by time-gated luminescence microscopy under excitation at 365 nm. Consequently, they are well adapted for in vitro imaging on cell cultures and flow cytometry devices.

To conclude, the CLUSTOP project was a logical extension of the research recently developed by the partners on the luminescent nanoparticles. In this project the combined inclusion of up-conversion nanocrystals together with clusters in the silica nanoparticles were allowed the achievement of both NIR-excitable and NIR-emitting nanoparticles that will be suitable for applications in the biotechnologies.

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The preparation of colloidal systems based on silica nanoparticles (noted X@SiO2, X= phosphors) which would be luminescent in the near infrared (NIR) field, non-toxic and resistant against aging is still an up-to-date technological challenge. This emission window (600-1000 nm) is an important property for applications in biotechnologies since it corresponds to the minimum of absorption of the tissues. Currently the main phosphors used for emission in the NIR are organic dyes or inorganic quantum dots (QDs) based on the elements Cd, Pb or As. The principal drawback of the organic phosphors is their premature aging under excitation (photobleaching) and QDs on their side are blinking, highly toxic and have a bad environmental impact.

Considering this context, the CLUSTOP project aims at elaborating new non-toxic and NIR-emitting phosphorescent nanoparticles, and at studying their physicochemical and toxicological properties. For this purpose, “up-conversion” nanocrystals will be introduced along with clusters into silica particles in order to obtain silica particles that will be photo-excitated in the NIR and able to emit in the same region. In parallel, noble metal nanocrystals (Au) will be introduced along with cluster into silica particles in order to obtain an enhancement of the NIR emission signal by resonant energy transfer between noble metal and metal atoms clusters. This project relies on the recent results obtained by P1 and P3 on the elaboration of ?-Fe2O3-Cs2Mo6X14@SiO2 nanoparticles where the units [Mo6X14]2- are highly dispersed in silica matrix around magnetic center (nanocrystals of ?-Fe2O3) in order to create bifunctional nanoparticles (magnetic and luminescent). In this project the new cluster@SIO2 nanoparticles will be synthesized by microemulsion process from transition metal atom clusters synthesized by solid state chemistry [Clusters = [M6X14]n- (M = Mo, Re; X = S, OH, Cl, Br, I; n = 2, 4)]. Those nanoparticles will be mainly based in a silica matrix controlled in size (10-100 nm). The silica matrix has been chosen because it is transparent in the NIR field, biocompatible, easily functionalizable and it offers numerous potential applications. Moreover, from optical point of view, clusters compounds are phosphorescent with high quantum yield and life time from 10 to 100 microsecond, so they gather the two assets of the molecular and inorganic phosphors: the nanometric size of organic dyes and the photobleaching resistance of QDs. Indeed [M6X14]2- units are currently the smallest inorganic nanometric entity resistant to photobleaching and free of toxic elements, which emit in the NIR field.

CLUSTOP is a 3-year research project which relies on the expertise and complementing skills of chemists, physicists, physicochemists and biologists originally from 3 partnered laboratories (P). Mastering those competences will ensure the success of the project. To conclude, the CLUSTOP project is a logical extension of the research recently developed by the mentioned partners on the cluster based luminescent nanoparticles. In this project the combined inclusion of noble metal or upconverting nanocrystals together with clusters in the silica nanoparticles will allow the achievement of both NIR-excitable and NIR-emitting nanoparticles that will be suitable for applications in the biotechnologies. It is a fundamental and multidisciplinary research program which will allow the preparation of nanomaterials with applications in the field of biotechnologies.