Stabilisation de nanoparticules dans l'eau par des copolymères à blocs

Dans ce travail on a développé une nouvelle stratégie de stabilisation de nanoparticules dans l'eau. Cette stratégie se base sur l'utilisation de copolymères amphiphiles, capables de s'auto-organiser autour des nanoparticules. Comme modèle on a choisi des copolymères à blocs (diblocs et triblocs) à base de poly(oxyéthylène) et de poly(oxypropylène). La stabilisation de nanoparticules d'or a pu être étudiée grâce à leurs propriétés optiques. On a démontré que la présence et la longueur de la chaîne hydrophobe sont essentielles pour la stabilisation. Ensuite, différentes techniques d'analyse (DDL, MET, SANS, Cryo-MET...) ont permis de montrer que les copolymères s'adsorbent à la surface des nanoparticules, même en l'absence de micelle en solution (C<CMC). Enfin, nous démontrons la faible cytotoxicité des nanoparticules stabilisées par ces polymères. Mots clés : stabilisation dans l'eau, polymères à blocs, nanoparticules d'or, résonnance plasmon de surface, nanostructure, cytotoxicité.We have developed a new strategy to stabilize nanoparticles in water. This strategy is based on the use of amphiphilic copolymers capable to self-assemble around the nanoparticles. We have chosen amphiphilic neutral block copolymers (diblocks and triblocks) based on poly(ethylene oxide) and poly(propylene oxide) to test this strategy. The aggregation state of gold nanoparticles has been studied using their optical properties. We have shown that the presence of a hydrophobic chain and its length are essential for the stability. Different techniques such as (DLS, TEM, cryo-TEM, and SANS...) have shown that in the presence of AuNps, under conditions in which micelles are not formed (C < CMC), polymer is adsorbed on AuNps forming large globules. Finally, we have demonstrated a low cytotoxicity effect of nanoparticles stabilized by these polymers. Keywords: stabilization in water, block copolymers, gold nanoparticles, surface plasmon resonance band, nanostructure, cytotoxicity

Embedding colloidal nanoparticles inside mesoporous silica using gas expanded liquids for high loading recyclable catalysts

The ability to tune the structural and chemical properties of colloidal nanoparticles (NPs), make them highly advantageous for studying activity and selectivity dependent catalytic behaviour. Incorporating pre-synthesized colloidal NPs into porous supports materials remains a challenge due to poor wetting and pore permeability. In this report monodisperse, composition controlled AgPd alloy NPs were synthesised and embedded into SBA-15 using supercritical carbon dioxide and hexane. Supercritical fluid impregnation resulted in high metal loading without the requirement for surface pre-treatments. The catalytic activity, reaction profiles and recyclability of the alloy NPs embedded in SBA-15 and immobilised on non-porous SiO2 are evaluated. The NPs incorporated within the SBA-15 porous network showed significantly greater recyclability performance compared to non-porous SiO2

Gold nanoparticles: synthesis, characterization, and bioconjugation

Gold nanoparticles (Au NPs) with diameters ranging between 4-150 nm have been synthesized in water. The strong reducing agent sodium borohydride (NaBH4) was used to produce small Au NPs with diameter about 4 +_1 nm. 15 and 30 nm Au NPs were obtained by a slightly modified Turkevich and Frens method using sodium citrate as both reducing and stabilizing agent at high temperature. The attempt to produce Au NPs with diameter larger than 30-40 nm by the Turkevich method resulted in an increase in the polydispersity and the shape diversity of the final Au NPs, indicating the importance of the trial of new reducing agents in the production of Au NPs especially for diameters above 40 nm. Therefore, hydroxylamine-o-sulfonic acid (NH2SO4H) (HOS) was used here for the first time as a new reducing agent for HAuCl4 at room temperature to produce Au NPs with diameter of about 60, 90 and 150 nm. This new method using HOS is an extension of the approaches described to produce Au NPs with diameter above 40 nm by direct reduction. The obtained nanoparticles were characterized using uv-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Further biocojuguation on 15, 30 and 90 nm Au NPs were performed by grafting covalently Apolipoprotein E (ApoE) and Bovine Serum Albumin (BSA) through an ethylene glycol-N-hydroxysuccinimide linker (NHS-PEG-S-S-PEG-NHS) making them very attractive for drug delivery and cell targeting. Finally, functionalized polyethylene glycol-based thiol polymers were also used to stabilize the pre-synthesized Au NPs-PEG-Protein

Bioconjugated gold nanoparticles enhance cellular uptake: a proof of concept study for siRNA delivery in prostate cancer cells

The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer

Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation

Metastatic prostate cancer is a leading cause of cancer-related death in men and current chemotherapies are largely inadequate in terms of efficacy and toxicity. Hence improved treatments are required. The application of siRNA as a cancer therapeutic holds great promise. However, translation of siRNA into the clinic is dependent on the availability of an effective delivery system. Gold nanoparticles (AuNPs) are known to be effective and non-toxic siRNA delivery agents. In this study, a stable gold nanosphere coated with poly(ethylenimine) (PEI) was prepared to yield PEI capped AuNPs (Au-PEI). The PEI was further conjugated with the targeting ligand anisamide (AA, is known to bind to the sigma receptor overexpressed on the surface of prostate cancer cells) to produce an anisamide-targeted nanoparticle (Au-PEI-AA). The resulting untargeted and targeted nanoparticles (Au-PEI and Au-PEI-AA respectively) were positively charged and efficiently complexed siRNA. Au-PEI-AA mediated siRNA uptake into PC3 prostate cancer cells via binding to the sigma receptor. In addition, the Au-PEI-AA·siRNA complexes resulted in highly efficient knockdown of the RelA gene (∼70%) when cells were transfected in serum-free medium. In contrast, no knockdown was observed in the presence of serum, suggesting that adsorption of serum proteins inhibits the binding of the anisamide moiety to the sigma receptor. This study provides (for the first time) proof of principle that anisamide-labelled gold nanoparticles can target the sigma receptor. Further optimisation of the formulation to increase serum stability will enhance its potential to treat prostate cancer

Gold nanoparticles enlighten the future of cancer theranostics

Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bioimaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance). As a new concept, termed “theranostics,” multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed

D2B-Functionalized Gold Nanoparticles: Promising Vehicles for Targeted Drug Delivery to Prostate Cancer

Despite the multitude of therapeutic agents available to treat prostate cancer (PC), there are still no effective and safe measures to treat the tumor. It remains a challenge to develop a simple approach to target PC with specific antibodies. In our study, D2B monoclonal antibodies against a prostate-specific membrane antigen (PSMA) were used. We investigated the functionalization of gold nanoparticles (AuNPs) with D2B to generate favorable physicochemical and biological properties that mediate specific binding to PC. For this purpose, AuNPs with a size of about 25 nm were synthesized in water using sodium citrate as a reducing and stabilizing agent and then coated with D2B. Major physicochemical properties of naked and D2B-coated AuNPs were investigated by ultraviolet−visible (UV−vis) spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. The successful binding of D2B to AuNPs-citrate caused a 15 nm red shift in the UV−vis. This was assessed by DLS as an increase in zeta potential from ∼−45 to ∼−23 mV and in the size of AuNPs from ∼25 to ∼63 nm. Scanning electron microscopy confirmed the size shift of AuNPs, which was detected as an exterior organic layer of D2Bs surrounding each AuNP. Even at high exposure levels of the bioconjugates, PSMA-PC-3 cells exhibited minimal cytotoxicity. The specific and dose-dependent binding of AuNPs-D2B to PC-3- PSMA cells was validated by flow cytometry analysis. Our data provide effective drug delivery systems in PC theranostics

Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: a formulation strategy for siRNA delivery

The potential of RNA interference (RNAi)-based therapeutics for cancer has received much attention; however, delivery of RNAi effectors, such as small interfering RNA (siRNA), remains an obstacle to clinical translation. Non-viral delivery vectors have been used extensively to enhance siRNA delivery. Recently, the potential of gold nanoparticles (AuNPs) for transporting drugs, proteins and genetic materials has been demonstrated. Previously, our laboratory synthesised positively charged, surfactant-free AuNPs in water by the reduction of gold (III) chloride (AuCl3) using hydroxylamine hydrochloride (NH2OH·HCl) in the presence of l-cysteine methyl ester hydrochloride (HSCH2CH(NH2)COOCH3·HCl) as a capping agent. These AuNPs, which achieve higher cell viability in comparison to cetyl trimethyl ammonium bromide (CTAB, a surfactant)-capped counterparts, have demonstrated potential for siRNA delivery. However, it is well known that systemic administration of cationic delivery systems without biological stablising moieties causes non-specific binding with negatively charged serum proteins, resulting in particle aggregation and opsonisation. Consequently, highly stable AuNPs capped with l-cysteine methyl ester hydrochloride conjugated to poly(ethylene glycol) (PEG) were synthesised in this study. PEGylation enhanced the biocompatibility of the AuNPs by reducing toxicity in a range of cell types, by inhibiting interaction with serum proteins thus avoiding aggregation, and, by providing protection against degradation by nucleases. Moreover, these PEGylated AuNPs formed nanoparticles (NPs) with siRNA (which was first compacted with protamine), and had a diameter within the nanoscale range (∼250nm) and a near neutral surface charge (∼10mV). In the future a bifunctional PEG chain on the AuNPs (i.e., SH-PEG-NH2, SH-PEG-COOH) will be used to facilitate conjugation of a targeting ligand to enhance cell specific uptake