Influence of the synthetic method on the properties of two-photon-sensitive mesoporous organosilica nanoparticles

International audienceHerein we report the modulation of the properties of mesoporous silica nanoparticles (NPs) via various synthetic approaches. Three types of elaborations were compared, one in aqueous media at 25 °C, and the other two at 80 °C in water or in a water–ethanol mixture. For all these methods, an alkoxysilylated two-photon photosensitizer (2PS) was co-condensed with tetraethylorthosilicate (TEOS) in the presence of cetyltrimethylammonium bromide (CTAB), leading to five two-photon-sensitive mesoporous silica (M2PS) NPs. The M2PS NP porous structure could be tuned from radial to worm-like and MCM-41 types of organization. Besides, the 2PS precursor spatial dispersion was found to be highly dependent on both the 2PS initial concentration and the elaboration process. As a result, two-photon properties were modulated by the choice of the synthesis, the best results being found in aqueous media at 25 or 80 °C. Finally, the M2PS NPs were used for in vitro two-photon imaging of cancer cells

TWO-PHOTON-ACTUATED THERANOSTIC NANOMEDICINE FOR CANCER TREATMENT

La nanomédecine activée à deux-photon est devenue l'un des principaux candidats à l'accomplissement de la sélectivité spatiotemporelle nécessaire pour la nanomédecine. En effet, la raison d'être de l'application médicale de nanotechnologie dans le domaine du traitement du cancer est de diminuer et supprimer les effets secondaires causés par les techniques actuelles telles que la chimiothérapie et la radiothérapie, à cause de leur manque de sélectivité. Parmi diverses nanoparticules (NPs), les nanoparticules de silice mésoporeuse (MSN) ont attiré une attention croissante dans la dernière décennie pour leur faible cytotoxicité, leur internalisation cellulaire et excrétion, et leur capacité de combiner de nombreuses fonctions à la fois pour le diagnostique et la thérapie de cancers via un seul nanovéhicule : l'ainsi appelée nanomédecine théranostique.Dans cette thèse, des MSN pour l'activation à un et deux-photon d'imagerie par fluorescence, de délivrance de principe actifs et d'acides nucléiques, et de photothérapie dynamique (PTD), seront présentées. Premièrement, le relargage contrôlé de molécules encapsulées dans des MSN fonctionnalisées avec des nanovalves est considéré par effet plasmonique. La photodégradation contrôlée de la silice soumise à l'effet photothermique de NPs d'or est ensuite étudiée. Deuxièmement, l'activation biphotonique est considérée pour la délivrance contrôlée de molécules anticancéreuses in-vitro par avec des nano-rotor et des nano-valves, ainsi que la fonctionnalisation de surface des NPs par des dérivés d'ammonium- azobenzene pour la délivrance d'acides nucléiques. Troisièmement, des MSN multifonctionnelles incorporant des photosensibilisateurs à deux-photon sont systématiquement étudiées en termes de leurs propriétés optiques et photophysiques; la sélection du meilleur matériau est suivie d'applications biomédicales in-vitro.De plus, deux types de nanomatériaux émergeant sont également élaborés pour la nanomédecine activée à deux-photon, des NPs de polysilsesquioxane pontés (BS) et d'organosilice mésoporeuse périodiques (PMO). Ces matériaux furent élaborés sans précurseur de silice (tétraéthoxysilane par exemple), et seulement à partir de bis- ou multi-organoalkoxysilane, afin d'obtenir le plus haut pourcentage de matière organique pour l'application ciblée. En conséquence, des NPs de BS et de PMO hybrides à base de disulfures se révélèrent être des outils biodégradables, et les NPs à base de photosensibilisateurs furent appliquées pour la PTD à deux-photon. Des NPs de BS et de cœur-coquille d'or-BS sont synthétisées pour d'efficaces imagerie et PTD à deux-photon, tandis que des NPs de PMO servirent de nano-plateformes théranostiques. En outre, diverse NPs de PMO multipodes à surface spécifique très élevées sont présentées pour la construction de structuration complexe à l'échelle nanométrique.Enfin, des nano-conteneurs d'MSN composées de cœur d'oxyde de fer (Fe3O4@MSN) sont décrites pour de multiples applications. D'une part, l'élaboration de NPs MSN (et PMO) magnétiques sensibles à deux-photon est étudiée en tant que perspective pour la délivrance de gène combinant l'imagerie par résonance magnétique. D'autre part, les conteneurs de Fe3O4@MSN sont misent en œuvre et appliqués pour la dépollution de métaux lourds via la fonctionnalisation d'un ligand de type acide diéthylène triamine penta acétique. L'augmentation de l'efficacité de la dépollution est étudiée par la fonctionnalisation de la surface extérieure et/ou des pores des [email protected] actuated nanomedicine has become one of the main proponents for the achievement of the spatiotemporal selectivity needed for nanomedicine. Indeed, the raison d'être of the medical application of nanotechnology in the field of cancer treatment is to lower and suppress the side effects caused by current techniques such as chemotherapy and radiotherapy, due to their lack of selectivity. Among various nanoparticles (NPs), mesoporous silica nanoparticles (MSN) have attracted increasing attention over the past decade for their low cytotoxicity, cellular internalization and excretion, and the ability to carry multiple features for both the diagnosis and therapy of cancers in a single nanovehicle: the so-called theranostic nanomedicine.In this dissertation, I will describe MSN for one and/or two-photon-actuated fluorescence imaging, drug-delivery, gene delivery and photodynamic therapy (PDT). First, plasmonically-triggered cargo delivery via MSN nanovalves and designed mesoporous silica photodegradation is presented. Then, in-vitro two-photon-triggered drug delivery with azobenzene-functionalized MSN such as nanoimpellers and fluorescent nanovalves, along with preliminary studies of gene delivery via ammonium-functionalized nanoimpellers are discussed. Multifunctional MSN incorporating a two-photon photosensitizer are systematically studied in terms of the resulting optical and photophysical properties of the NPs, and then used for in-vitro biomedical applications.Furthermore, two kinds of emerging nanomaterials are also designed for two-photon actuated nanomedicine, bridged silsesquioxane (BS) and periodic mesoporous organosilica (PMO) NPs. These nanomaterials are elaborated without silica precursor (e.g. tetraethoxysilane) and solely with bis- or tetra-organoalkoxysilanes, thus providing materials with the highest organic content for the targeted applications. Consequently, disulfide-based hybrid BS and PMO NPs were elaborated as biodegradable nanomedical tools, and photosensitizer-based BS and PMO NPs were used for efficient in-vitro PDT. BS and gold-BS core-shells NPs are constructed for ultrabright two-photon imaging and efficient PDT, while two-photon functionalized PMO NPs serve as theranostic nanocarriers. Besides, versatile multipodal ethylene-benzene PMO NPs with very high surface areas are presented as a promising strategy for the design of structural complexities at the nanoscale.Finally, iron oxide core MSN shell (Fe3O4@MSN) nanocontainers are described for versatile applications. The design of two-photon-sensitive magnetic MSN and PMO core-shell nanovehicles is presented as a perspective for gene delivery and magnetic resonance imaging. Furthermore, Fe3O4@MSN containers are constructed for heavy metal removal of twelve of the most toxic metal ions through the diethylene triamine pentaacetic acid (DTPA) ligand. The enhancement of the pollutant removal efficiency is studied by selective surface and/or porous DTPA functionalizations

Nanovalve-controlled cargo release activated by plasmonic heating

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The enzymes, Mesoporous silica-Based Nanomaterials and Biomedical Applications, Fuyuhiko Tamanoi Ed

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Nanovalve-Controlled Cargo Release Activated by Plasmonic Heating

The synthesis and operation of a light-operated nanovalve that controls the pore openings of mesoporous silica nanoparticles containing gold nanoparticle cores is described. The nanoparticles, consisting of 20 nm gold cores inside ∼150 nm mesoporous silica spheres, were synthesized using a unique one-pot method. The nanovalves consist of cucurbit[6]­uril rings encircling stalks that are attached to the ∼2 nm pore openings. Plasmonic heating of the gold core raises the local temperature and decreases the ring–stalk binding constant, thereby unblocking the pore and releasing the cargo molecules that were preloaded inside. Bulk heating of the suspended particles to 60 °C is required to release the cargo, but no bulk temperature change was observed in the plasmonic heating release experiment. High-intensity irradiation caused thermal damage to the silica particles, but low-intensity illumination caused a local temperature increase sufficient to operate the valves without damaging the nanoparticle containers. These light-stimulated, thermally activated, mechanized nanoparticles represent a new system with potential utility for on-command drug release

Two-Photon-Excited Silica and Organosilica Nanoparticles for Spatiotemporal Cancer Treatment

International audienceCoherent two‐photon‐excited (TPE) therapy in the near‐infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by a 3D spatial resolution of 1 µm3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE‐NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well‐established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side‐effect therapies via TPE‐NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two‐photon absorbers for drug delivery and diagnosis. Currently, most light‐actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two‐photon‐sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE‐NIR ultrasensitive diagnosis and therapy

Organosilica hybrid nanomaterials with a high organic content: syntheses and applications of silsesquioxanes

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Syntheses and applications of periodic mesoporous organosilica nanoparticles

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