Single phase microreactor for the continuous, high-temperature synthesis of <4¿nm superparamagnetic iron oxide nanoparticles

The reproducibility of key nanomaterial features is essential in nanomedicine applications where small changes of physical characteristics often lead to a very different behavior. In this regard, continuous microreactors are often advocated as a means to achieve highly precise synthesis of nanomaterials. However, when the synthesis must take place at high temperatures the use of these devices becomes restricted in terms of materials and practical problems (e.g. plugging of microchannels). Here we present the continuous synthesis of ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) through a polyol-based process at high temperatures (>200 °C). The microfluidic reactor designed allows SPION production at residence times under 1 min, was able to work continuously for 8 h without channel blockage and reached high production yields by coupling microreactors using stacked plates. The effect of operating conditions was optimized to produce homogeneous particles with a narrow particle size distribution. In summary, the microreactor developed in this work enables easy-to scale up, reproducible continuous production of SPIONs

Beyond gold: rediscovering tetrakis-(hydroxymethyl)-phosphonium chloride (THPC) as an effective agent for the synthesis of ultra-small noble metal nanoparticles and Pt-containing nanoalloys

The use of tetrakis-(hydroxymethyl)-phosphonium chloride (THPC) as simultaneous reducing agent and stabilizing ligand has been extended to the single-step synthesis at room temperature of a wide variety of monometallic nanoparticles and bi-/tri- metallic nanoalloys containing noble metals with potential application in catalysis. The colloidal suspensions exhibit mean diameters below 4 nm with narrow size distributions and high stability in aqueous solution for long periods of time

Spontaneous formation of Au-Pt alloyed nanoparticles using pure nano-counterparts as starters: a ligand and size dependent process

In this work we investigate the formation of PtAu monodisperse alloyed nanoparticles by ageing pure metallic Au and Pt small nanoparticles (sNPs), nanoparticle size <5 nm, under certain conditions. We demonstrate that those bimetallic entities can be obtained by controlling the size of the initial metallic sNPs separately prepared and by selecting their appropriate capping agents. The formation of this spontaneous phenomenon was studied using HR-STEM, EDS, ionic conductivity, UV-Vis spectroscopy and cyclic voltammetry. Depending on the type of capping agent used and the size of the initial Au sNPs, three different materials were obtained: (i) AuPt bimetallic sNPs showing a surface rich in Au atoms, (ii) segregated Au and Pt sNPs and (iii) a mixture of bimetallic nanoparticles as well as Pt sNPs and Au NPs. Surface segregation energies and the nature of the reaction environment are the driving forces to direct the distribution of atoms in the bimetallic sNPs. PtAu alloyed nanoparticles were obtained after 150 h of reaction at room temperature if a weak capping agent was used for the stabilization of the nanoparticles. It was also found that Au atoms diffuse towards Pt sNPs, producing a surface enriched in Au atoms. This study shows that even pure nanoparticles are prone to be modified by the surrounding nanoparticles to give rise to new nanomaterials if atomic diffusion is feasible

Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: Effect of passive mixing

By using interdigital microfluidic reactors, monodisperse poly(d, l lactic-co-glycolic acid) nanoparticles (NPs) can be produced in a continuous manner and at a large scale (~10 g/h). An optimized synthesis protocol was obtained by selecting the appropriated passive mixer and fluid flow conditions to produce monodisperse NPs. A reduced NP polydispersity was obtained when using the microfluidic platform compared with the one obtained with NPs produced in a conventional discontinuous batch reactor. Cyclosporin, an immunosuppressant drug, was used as a model to validate the efficiency of the microfluidic platform to produce drug-loaded monodisperse poly(d, l lactic-co-glycolic acid) NPs. The influence of the mixer geometries and temperatures were analyzed, and the experimental results were corroborated by using computational fluid dynamic three-dimensional simulations. Flow patterns, mixing times, and mixing efficiencies were calculated, and the model supported with experimental results. The progress of mixing in the interdigital mixer was quantified by using the volume fractions of the organic and aqueous phases used during the emulsification–evaporation process. The developed model and methods were applied to determine the required time for achieving a complete mixing in each microreactor at different fluid flow conditions, temperatures, and mixing rates

In-situ preparation of ultra-small Pt nanoparticles within rod-shaped mesoporous silica particles: 3-D tomography and catalytic oxidation of n-hexane

The shape and porous configuration of supports are key parameters to design outstanding catalysts. However, the selection of a proper mesoporous support, such as SBA-15, by itself does not guarantee accessibility to catalytic sites. The distribution of the active phase and its stability are strongly related to the procedure used to deposit it on the catalytic substrate. Herein, we have prepared rod-shaped SBA-15 silica supports functionalized with amine groups to facilitate the electrostatic attraction and a good distribution of the resulting Pt-based catalytic nanoparticles along the pore walls. Additionally, the use of tetrakis-(hydroxymethyl)-phosphonium chloride (THPC) as both reductant and stabilizer is presented as a novel alternative for Pt nanoparticle synthesis. The behaviour of this catalyst in the total oxidation of n-hexane demonstrates high activity and excellent stability after 70 h on reaction stream. STEM-HAADF and 3-D tomography were used to confirm the presence of the metallic nanoparticles within the mesochannels and to corroborate their reduced sintering after reaction

Plasmodium falciparum Apicomplexan-Specific Glucosamine-6-Phosphate N-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage Development

UDP-N-acetylglucosamine (UDP-GlcNAc), the main product of the hexosamine biosynthetic pathway, is an important metabolite in protozoan parasites since its sugar moiety is incorporated into glycosylphosphatidylinositol (GPI) glycolipids and N- and O-linked glycans. Apicomplexan parasites have a hexosamine pathway comparable to other eukaryotic organisms, with the exception of the glucosamine-phosphate N-acetyltransferase (GNA1) enzymatic step that has an independent evolutionary origin and significant differences from nonapicomplexan GNA1s. By using conditional genetic engineering, we demonstrate the requirement of GNA1 for the generation of a pool of UDP-GlcNAc and for the development of intraerythrocytic asexual Plasmodium falciparum parasites. Furthermore, we present the 1.95 A resolution structure of the GNA1 ortholog from Cryptosporidium parvum, an apicomplexan parasite which is a leading cause of diarrhea in developing countries, as a surrogate for P. falciparum GNA1. The indepth analysis of the crystal shows the presence of specific residues relevant for GNA1 enzymatic activity that are further investigated by the creation of site-specific mutants. The experiments reveal distinct features in apicomplexan GNA1 enzymes that could be exploitable for the generation of selective inhibitors against these parasites, by targeting the hexosamine pathway. This work underscores the potential of apicomplexan GNA1 as a drug target against malaria. IMPORTANCE Apicomplexan parasites cause a major burden on global health and economy. The absence of treatments, the emergence of resistances against available therapies, and the parasite''s ability to manipulate host cells and evade immune systems highlight the urgent need to characterize new drug targets to treat infections caused by these parasites. We demonstrate that glucosamine-6-phosphate N-acetyltransferase (GNA1), required for the biosynthesis of UDP-N-acetylglucosamine (UDP-GlcNAc), is essential for P. falciparum asexual blood stage development and that the disruption of the gene encoding this enzyme quickly causes the death of the parasite within a life cycle. The high-resolution crystal structure of the GNA1 ortholog from the apicomplexan parasite C. parvum, used here as a surrogate, highlights significant differences from human GNA1. These divergences can be exploited for the design of specific inhibitors against the malaria parasite

In Cellulo Bioorthogonal Catalysis by Encapsulated AuPd Nanoalloys. Overcoming Intracellular Deactivation

Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cell