ARTICLE pubs.acs.org/Langmuir
One-Pot Synthesis of Hybrid Multifunctional Silica Nanoparticles with Tunable Coating by Click Chemistry in Reverse W/O Microemulsion Cedric Tissandier,† No€el Diop,†,‡ Matteo Martini,‡ Stephane Roux,‡,§ Olivier Tillement,‡ and Thierry Hamaide*,† †
Ingenierie des Materiaux Polymeres, Universite Claude Bernard Lyon 1, IMP@Lyon1, UMR CNRS 5223, 15 Bd Latarjet, 69622 Villeurbanne Cedex, France ‡ Laboratoire de Physico-Chimie des Materiaux Luminescents, Universite Claude Bernard Lyon 1, UMR CNRS 5620, 69622 Villeurbanne Cedex, France ABSTRACT: Multifunctional hybrid silica nanoparticles with a fluorescent core and tunable organic or polymeric shell can easily be prepared by a solgel process followed by 1,3 dipolar cycloaddition (CuAAC) in the same reverse quaternary W/O microemulsion. Compared to a classical multistep process, this one-pot synthesis reduces greatly the number of purification steps and avoids aggregation phenomena. The confinement of reactants inside the micellar system gives rise to a noticeable increase of the CuAAC reaction rate. In addition, using simultaneously two different substrates for CuAAC on silica allows us to obtain directly multifunctional hybrid nanoparticles displaying a double grafting without any separation or purification steps except the final recovery by centrifugation, which opens the door to a tunable coating of the nanoparticles. Particularly, the hydrophiliclipophilic balance of the coating can be adjusted by implementing the pertinent MPEG:dodecyl azide ratio. As an application, the great versatility of this strategy has been proved by the one-pot synthesis of fluorescent silica nanoparticles with a PEG coating and encapsulating silver clusters.
’ INTRODUCTION Very intense research activities have been devoted during the past decade to the elaboration of hybrid nanoparticles in order to gather several complementary properties in a same very small object. As a first example, Weissleder reported pioneering works dealing with the development of triple label nanoparticles.1 Core/shell structure nanoparticles based on polysiloxane coated gadolinium oxide doped with Tb3+ ions were found to be efficient for the detection of biomolecules.2 As another example, iron oxide nanoparticles coated with a PEGylated copolymer were prepared and used as contrast agents for in vivo magnetic resonance imaging (MRI).3 In the same way, multimodal contrast agents for MRI were developed from the previously described hybrid nanoparticles based on Gd2O3 coated with a polysiloxane shell, encapsulating an organic fluorophore and carrying PEG chains onto their surface.4 More recently, it was also demonstrated that adding gold inclusions within silica particles containing fluorescein allows the suppression of the self-quenching phenomenon.5,6 All of these examples illustrate well the concept of a multifunctional hybrid platform, namely a very small object engulfing organic and/or inorganic nanoparticles and displaying additional functionalities such as a stealthy character, a molecular recognition or a reduced toxicity by a pertinent coating. In addition, the colloidal stability of these nanoparticles over a long period has to be ensured. Some interesting coatings may be planned in order to fulfill two requirements simultaneously, the best known of them being PEG: in addition to r 2011 American Chemical Society
the steric stabilization, the PEG coating reduces the detection of nanoparticles or liposomes by the immune system and then the reticular endothelial uptake of nanoparticles, thus increasing their circulation time in the body .7,8 Therefore, the final properties and further applications of these multifunctional hybrid platforms are closely related to their surface chemistry, which needs to be well-controlled. A first way consists in using well-defined copolymers as polymer surfactants for the steric stabilization of polymer nanoparticles from polymer organic solutions by emulsification diffusion, precipitation, or any other appropriate physicochemical method.3,911 To do that, polymer surfactants seem to be more appropriate for the stabilization of colloidal polymer particles than smaller molecular surfactants such as sodium dodecyl surfactant because of their stronger adsorption on the particles interfaces, which slows the dynamic exchanges between the aqueous phase and polymer particles. In that case, there are no covalent bonds between organic or inorganic particles and the polymer coating. The covalent grafting can be achieved by using functional monomers or monomers able to react after their polymerization. For example, the covalent bonding of surfactants onto the surface of polymer particles in emulsion polymerization improves the Received: September 13, 2011 Revised: November 8, 2011 Published: November 08, 2011 209
dx.doi.org/10.1021/la203580q | Langmuir 2012, 28, 209–218
Langmuir
ARTICLE
functionalization of mesoporous silica nanoparticles, which have previously been obtained by the same solgel method, by pyrene moieties.25 We ensure the inner functionalization by the fluoresceine derivative, issued from FITC and APTES, as well as silver clusters engulfing. This approach allows synthesizing easily multifunctional hybrid nanoparticles with a tunable hydrophilic lipophilic balance coating. More interestingly, it was observed that the multifunctional hybrid silica nanoparticles can easily be prepared in an one-pot synthesis, namely the solgel process followed by CuAAC in the same reverse quaternary W/O microemulsion.
Scheme 1. General Strategy for the Elaboration of Functionalized Nanoparticles by CuAAc
’ EXPERIMENTAL SECTION Chemicals. Tetraethoxysilane (TEOS), (3-aminopropyl) triethoxysilane (APTES), and O-propargyloxy-N-triethoxy silylpropyl carbamate (PTESC) were purchased from Aldrich Chemicals. Dodecyl azide, benzyl azide, α-methoxy-ω-azido-poly(ethylene glycol) (referred as MPEG-N3), and α-methoxy-ω-propargyl ether-poly(ethylene glycol) (referred as MPEG-CtCH) were issued from 1-bromododecane, benzyl chloride, and α-methoxy poly(ethylene glycol), respectively, according to previously described procedures.16,26 All of these reactants were characterized by NMR and FTIR (MPEGN3: νNtN 2106 cm1; MPEG—CtCH: νCtC 2111 cm1; C12H25N3: νNtN 2095 cm1). Characterization Techniques. Particles sizes were investigated by transmission electronic microscopy using a JEOL 2010F microscope operating at 200 kV. The samples were prepared by depositing a drop of a diluted colloidal solution on carbon grid (200 mesh) and allowing the water to evaporate at room temperature. The average size and the standard deviation are determined from the images. Direct measurement of the size distribution of the particles was also performed by dynamic light scattering using a Zetasizer NanoS PCS (photon correlation spectroscopy) from Malvern Instrument. The luminescence emission spectra were measured at room temperature using a Hitachi F-2500 spectrophotometer. The excitation wavelength was adjusted to 493 nm that corresponds to the absorption maximum for fluorescein dyes in aqueous solutions (0.1 N NaOH). Samples were diluted to have an optical density
