Supermagnetic Human Serum Albumin (HSA) Nanoparticles and PLGA-Based Doxorubicin Nanoformulation: A Duet for Selective Nanotherapy.

Predicting the ability of nanoparticles (NP) to access the tumor is key to the success of chemotherapy using nanotherapeutics. In the present study, the ability of the dual NP-based theranostic system to accumulate in the tumor was evaluated in vivo using intravital microscopy (IVM) and MRI. The system consisted of model therapeutic doxorubicin-loaded poly(lactide-co-glycolide) NP (Dox-PLGA NP) and novel hybrid Ce3/4+-doped maghemite NP encapsulated within the HSA matrix (hMNP) as a supermagnetic MRI contrasting agent. Both NP types had similar sizes of ~100 nm and negative surface potentials. The level of the hMNP and PLGA NP co-distribution in the same regions of interest (ROI, ~2500 µm2) was assessed by IVM in mice bearing the 4T1-mScarlet murine mammary carcinoma at different intervals between the NP injections. In all cases, both NP types penetrated into the same tumoral/peritumoral regions by neutrophil-assisted extravasation through vascular micro- and macroleakages. The maximum tumor contrasting in MRI scans was obtained 5 h after hMNP injection/1 h after PLGA NP injection; the co-distribution level at this time reached 78%. Together with high contrasting properties of the hMNP, these data indicate that the hMNP and PLGA NPs are suitable theranostic companions. Thus, analysis of the co-distribution level appears to be a useful tool for evaluation of the dual nanoparticle theranostics, whereas assessment of the leakage areas helps to reveal the tumors potentially responsive to nanotherapeutics.

Novel Nanocarrier Platform for Effective Treatment of Visceral Leishmaniasis.

Leishmaniasis is among the five parasitic diseases that still require the development of new drugs. Ultrasmall cerium (Ce3/4+) cation-doped maghemite (γ-Fe2O3) nanoparticles (NPs) were tested as a potential drug to treat visceral leishmaniasis, a disease affecting millions of people worldwide. The NPs were engineered for binding a polycationic branched polyethylenimine (PEI) polymer, thereby rupturing the single lysosome of these parasites and enabling entry of the anti-Leishmania drug, pentamidine. Exploiting the known lanthanide cation/complex-based coordinative chemical reactivity enabled the binding of both active agents onto the surface of the NPs. To optimize the fabrication of the cytotoxic NPs, optimization via a DoE (Design of Experiments) process was used to identify the optimal NP with toxicity against the two stages of the parasite, promastigotes, which propagate in the insect, and amastigotes, which infect the mammalian host. The screen identified a single optimized NP (DoE Opt) that was further examined in a mouse model of visceral leishmaniasis. Intravenous injection of the NPs had no adverse effects on the cellular composition or biochemical parameters of the blood, demonstrating no signs of systemic toxicity. The optimized NP was able to eradicate visceral disease caused by Leishmania donovani infection. The study demonstrates the versatile ability of the cerium-doped NPs to bind at least two cytotoxic ligands. This approach could be used for optimizing the binding of different drugs for the treatment of other diseases, including cancer. Since resistance to treatment with nanocarriers was not reported to date, such an approach could potentially overcome drug resistance that emerges when using soluble small molecule drugs.

Ultrasensitive haptoglobin biomarker detection based on amplified chemiluminescence of magnetite nanoparticles.

BACKGROUND: Haptoglobin is an acute-phase protein used as predicting diagnostic biomarker both in humans (i.e., diabetes, ovarian cancer, some neurological and cardiovascular disorders) and in animals (e.g., bovine mastitis). The latter is a frequent disease of dairy industry with staggering economical losses upon decreased milk production and increased health care costs. Early stage diagnosis of the associated diseases or inflammation onset is almost impossible by conventional analytical manners. RESULTS: The present study demonstrates a simple, rapid, and cost-effective label-free chemiluminescence bioassay based on magnetite nanoparticles (MNPs) for sensitive detection of haptoglobin by employing the specific interaction of hemoglobin-modified MNPs. The resulting haptoglobin-hemoglobin complex inhibits the peroxidase-like activity of luminol/H2O2-hemoglobin-MNPs sensing scheme and reduces the chemiluminescence intensities correspondingly to the innate haptoglobin concentrations. Quantitative detection of bovine haptoglobin was obtained within the range of 1 pg mL-1 to 1 µg mL-1, while presenting 0.89 pg mL-1 limit of detection. Moreover, the influence of causative pathogenic bacteria (i.e., Streptococcus dysgalactiae and Escherichia coli) and somatic cell counts (depicting healthy, sub-clinical and clinical mastitis) on the emitted chemiluminescence radiation were established. The presented bioassay quantitative performances correspond with a standardized assay kit in differentiating dissimilar milk qualities. CONCLUSIONS: Overall, the main advantage of the presented sensing concept is the ability to detect haptoglobin, at clinically relevant concentrations within real milk samples for early bio-diagnostic detection of mastitis and hence adjusting the precise treatment, potentially initiating a positive influence on animals' individual health and hence on dairy farms economy.

Conformal carbon coating on WS2 nanotubes for excellent electrochemical performance of lithium-ion batteries.

WS2 nanotubes with carbon coatings in a core-shell structure (i.e. WS2@C) are synthesized through a facile method based on the Lewis acid-activated thioglycosylation chemistry. The obtained WS2@C shows a conformal coverage of conductive amorphous carbon on the surface of WS2 after thermal treatment, with the thickness of carbon layer being controlled by adjusting the molar ratios of saccharide to nanotube during the synthesis process. When applied in lithium-ion batteries, the WS2@C structures show higher reversible capacity of 638 mAh g-1 at a current density of 500 mA g-1 and significantly improved cycling stability as compared to the pristine WS2 nanotubes. Post-mortem examinations of the electrode materials reveal that the carbon coatings could preserve the morphology of WS2 nanotubes and assist in forming stable solid electrolyte interface layers, leading to enhanced cycling stability. As such, the WS2@C structures show great potential in the application of lithium-ion batteries for achieving excellent electrochemical performances.

Bifunctional Carbon-Dot-WS2 Nanorods for Photothermal Therapy and Cell Imaging.

Multifunctional nanoparticles have attracted significant interest as biomedical vehicles, combining diagnostic, imaging, and therapeutic properties. We describe herein the construction of new nanoparticle conjugates comprising WS2 nanorods (NRs) coupled to fluorescent carbon dots (C-dots). We show that the WS2 -C-dot hybrids integrate the unique physical properties of the two species, specifically the photothermal activity of the WS2 NRs upon irradiation with near-infrared (NIR) light and the excitation-dependent luminescence emission of the C-dots. The WS2 -C-dot NRs have been shown to be non-cytotoxic and have been successfully employed for multicolour cell imaging and targeted cell killing under NIR irradiation, pointing to their potential utilization as effective therapeutic vehicles.

Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer.

BACKGROUND: Functionalized nanoparticles (NPs) are one promising tool for detecting specific molecular targets and combine molecular biology and nanotechnology aiming at modern imaging. We aimed at ligand-directed delivery with a suitable target-biomarker to detect early pancreatic ductal adenocarcinoma (PDAC). Promising targets are galectins (Gal), due to their strong expression in and on PDAC-cells and occurrence at early stages in cancer precursor lesions, but not in adjacent normal tissues. RESULTS: Molecular probes (10-29 AA long peptides) derived from human tissue plasminogen activator (t-PA) were selected as binding partners to galectins. Affinity constants between the synthesized t-PA peptides and Gal were determined by microscale thermophoresis. The 29 AA-long t-PA-peptide-1 with a lactose-functionalized serine revealed the strongest binding properties to Gal-1 which was 25-fold higher in comparison with the native t-PA protein and showed additional strong binding to Gal-3 and Gal-4, both also over-expressed in PDAC. t-PA-peptide-1 was selected as vector moiety and linked covalently onto the surface of biodegradable iron oxide nanoparticles (NPs). In particular, CAN-doped maghemite NPs (CAN-Mag), promising as contrast agent for magnetic resonance imaging (MRI), were selected as magnetic core and coated with different biocompatible polymers, such as chitosan (CAN-Mag-Chitosan NPs) or polylactic co glycolic acid (PLGA) obtaining polymeric nanoparticles (CAN-Mag@PNPs), already approved for drug delivery applications. The binding efficacy of t-PA-vectorized NPs determined by exposure to different pancreatic cell lines was up to 90%, as assessed by flow cytometry. The in vivo targeting and imaging efficacy of the vectorized NPs were evaluated by applying murine pancreatic tumor models and assessed by 1.5 T magnetic resonance imaging (MRI). The t-PA-vectorized NPs as well as the protease-activated NPs with outer shell decoration (CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac) showed clearly detectable drop of subcutaneous and orthotopic tumor staining-intensity indicating a considerable uptake of the injected NPs. Post mortem NP deposition in tumors and organs was confirmed by Fe staining of histopathology tissue sections. CONCLUSIONS: The targeted NPs indicate a fast and enhanced deposition of NPs in the murine tumor models. The CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac interlocking steps strategy of NPs delivery and deposition in pancreatic tumor is promising.

Unique Surface Modification of Silica Nanoparticles with Polyethylenimine (PEI) for siRNA Delivery Using Cerium Cation Coordination Chemistry.

The discovery of RNA interference (RNAi) as a naturally occurring mechanism for gene knockdown has attracted considerable attention toward the use of small interfering RNAs (siRNAs) for therapeutic purposes. The main obstacles of harnessing siRNAs as drugs are their inefficient delivery to cells and off-target effect making clinical applications very challenging. The positively charged, branched 25 kDa polyethylenimine (b-PEI) polymer is widely regarded as one of the most efficient nonviral commercially available transfection agents. However, it has also been shown that 25 kDa b-PEI is highly cytotoxic and can readily lead to cell death. In this specific context, this study presents the preparation and characterization of innovative 25 kDa b-PEI-decorated polycationic silica nanoparticles (SiO2 NPs) for cellular siRNA delivery and subsequent gene silencing. A new method of b-PEI attachment onto the SiO2 NP surface has been developed that makes use of cerium(III) cations (Ce(3+)), a lanthanide group element, as an effective noncovalent inorganic linker between both polyNH2-SiO2 nanoparticle (SPA NPs) surface and polycationic 25 kDa b-PEI polymer. Two resulting novel SPA-Ce-PEI NPs consist of similar amounts of b-PEI, while possessing different amounts of Ce(3+). Various analytical techniques (TEM, DLS, ζ potential, ICP-AES, and TGA) have been used to deeply characterize NPs physicochemical qualities. The observed results of Ce(3+)-dependent gene silencing and cytotoxic activities led us to conclusions about the role of Ce(3+)-N bonding during the chemical attachment of the 25 kDa b-PEI shell onto the NP surface.

Towards hybrid biocompatible magnetic rHuman serum albumin-based nanoparticles: use of ultra-small (CeLn)3/4+ cation-doped maghemite nanoparticles as functional shell.

Human serum albumin (HSA) is a protein found in human blood. Over the last decade, HSA has been evaluated as a promising drug carrier. However, not being magnetic, HSA cannot be used for biomedical applications such as magnetic resonance imaging (MRI) and magnetic drug targeting. Therefore, subsequent composites building on iron oxide nanoparticles that are already used clinically as MRI contrast agents are extensively studied. Recently and in this context, innovative fully hydrophilic ultra-small CAN-stabilized maghemite ((CeLn)(3/4+)-γ-Fe2O3) nanoparticles have been readily fabricated. The present study discusses the design, fabrication, and characterization of a dual phase hybrid core (rHSA)-shell ((CeLn)(3/4+)-γ-Fe2O3 NPs) nanosystem. Quite importantly and in contrast to widely used encapsulation strategies, rHSA NP surface-attached (CeLn)(3/4+)-γ-Fe2O3 NPs enabled to exploit both rHSA (protein functionalities) and (CeLn)(3/4+)-γ-Fe2O3 NP surface functionalities (COOH and ligand L coordinative exchange) in addition to very effective MRI contrast capability due to optimal accessibility of H2O molecules with the outer magnetic phase. Resulting hybrid nanoparticles might be used as a platform modular system for therapeutic (drug delivery system) and MR diagnostic purposes.

The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model.

BACKGROUND: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. RESULTS: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. CONCLUSIONS: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.

Real-time quantification of protein expression and translocation at individual cell resolution using imaging-dish-based live cell array.

Cell populations represent intrinsically heterogeneous systems with a high level of spatiotemporal complexity. Monitoring and understanding cell-to-cell diversity is essential for the research and application of intra- and interpopulation variations. Optical analysis of live cells is challenging since both adherent and nonadherent cells change their spatial location. However, most currently available single-cell techniques do not facilitate treatment and monitoring of the same live cells over time throughout multistep experiments. An imaging-dish-based live cell array (ID-LCA) has been developed and produced for cell handling, culturing, and imaging of numerous live cells. The dish is composed of an array of pico scale cavities-pico wells (PWs) embossed on its glass bottom. Cells are seeded, cultured, treated, and spatiotemporally measured on the ID-LCA, while each cell or small group of cells are locally constrained in the PWs. Finally, predefined cells can be retrieved for further evaluation. Various types of ID-LCAs were used in this proof-of-principle work, to demonstrate on-ID-LCA transfection of fluorescently tagged chimeric proteins, as well as the detection and kinetic analysis of their induced translocation. High variability was evident within cell populations with regard to protein expression levels as well as the extent and dynamics of protein redistribution. The association of these parameters with cell morphology and functional parameters was examined. Both the new methodology and the device facilitate research of the translocation process at individual cell resolution within large populations and thus, can potentially be used in high-throughput fashion.

Silica nanoparticles and polyethyleneimine (PEI)-mediated functionalization: a new method of PEI covalent attachment for siRNA delivery applications.

Small-interfering RNA (siRNA) is a synthetic double-stranded RNA that consists of approximately 21 nucleotides (nts). It induces degradation of target mRNAs in a sequence-specific manner by the RNA interference (RNAi) mechanism. Thus, siRNAs offer a potential strategy for silencing mutated or defective genes that cause a variety of human diseases. The main obstacles of harnessing siRNAs as drugs are their inefficient delivery to cells and off-target effect making clinical applications very challenging. To address these issues, researchers have studied a variety of nanocarrier systems for siRNA delivery. This study presents the design, fabrication, and full characterization of innovative polyethyleneimine (PEI)-decorated polycationic 34.2 ± 4.2 nm silica (SiO2) NPs for siRNA-mediated gene silencing. More specifically, a new means of introduction (covalent mode of attachment) of the polycationic 25 kDa PEI polymer onto the SiO2 NP surface has been developed that makes use of an effective electrophilic double Michäel acceptor, divinyl sulfone (DVS). The resulting novel SiO2-PEI nanoparticles (SPEI NPs) have been fully characterized using a wide range of analytical, spectroscopic, and microscopic methods (TEM, DLS, ζ potential, elemental analysis (EA), XPS, TGA, and FTIR). Disclosing quite low cytotoxicity due to this unique mode of PEI covalent grafting, SPEI NPs/siRNA polyplexes have been successfully tested for the induction of gene silencing using dual-reporter luciferase transfected human osteosarcoma U2OS cells. The corresponding gene silencing data showed a clear correlation between PEI/siRNA ratios, siRNA concentration(s), and the level of gene silencing. Moreover, these SPEI NPs have been demonstrated to be thermodynamically stable with an ability to efficiently bind siRNAs and induce silencing for at least a one-year-long storage.

Improved antibacterial and antibiofilm activity of magnesium fluoride nanoparticles obtained by water-based ultrasound chemistry.

Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. We recently reported on the antimicrobial and antibiofilm activities of nanosized magnesium fluoride (MgF(2)) nanoparticles (NPs) synthesized in ionic liquid using microwave chemistry. In this article, we describe a novel water-based synthesis of MgF(2) NPs using sonochemistry. The sonochemical irradiation of an aqueous solution of [Mg(OAc)(2)⋅(H(2)O)(4)] containing acidic HF as the fluorine ion source afforded crystalline well-shaped spherical MgF(2) NPs that showed much improved antibacterial properties against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus). We were also able to demonstrate that the antimicrobial activity was dependent on the size of the NPs. In addition, using the described sonochemical process, we coated glass surfaces and demonstrated inhibition of bacterial colonization for 7 days. Finally, the antimicrobial activity of MgF(2) NPs against established biofilms was also examined. Taken together our results highlight the potential to further develop the concept of utilizing these metal fluoride NPs as novel antimicrobial and antibiofilm agents. FROM THE CLINICAL EDITOR: In this article, the authors describe a novel aqueous synthesis of magnesium fluoride NPs using sonochemistry. These nanoparticles have improved antibacterial and antibiofilm activity compared to their counterparts with traditional synthesis methods.

Noninvasive Nanodiamond Skin Permeation Profiling Using a Phase Analysis Method: Ex Vivo Experiments.

Carbon-based nanoparticles (NPs) are widely used in nanotechnology. Among them, nanodiamonds (NDs) are suitable for biotechnology and are especially interesting for skin delivery and topical treatments. However, noninvasive detection of NDs within the different skin layers or analyzing their penetration ability is complicated due to the turbid nature of the tissue. The iterative multiplane optical properties extraction (IMOPE) technique detects differences in the optical properties of the measured item by a phase-image analysis method. The phase image is reconstructed by the multiplane Gerchberg-Saxton algorithm. This technique, traditionally, detects differences in the reduced scattering coefficients. Here, however, due to the actual size of the NDs, the IMOPE technique's detection relies on absorption analysis rather than relying on scattering events. In this paper, we use the IMOPE technique to detect the presence of the NDs within tissue-like phantoms. In addition, we perform ex vivo pigskin experiments to estimate the penetration of the NDs to the different skin layers and show that their presence reduces at deeper layers. The significance signal of the NDs within the epidermis, dermis, and fat layers gradually reduces, with t test significance values that are smaller than 10-4, 10-3, and 10-2, respectively. The IMOPE results are corroborated by TEM results and Franz-cell experiments. These results confirm that the IMOPE profiled the skin-permeation of the NDs noninvasively.

Magnetically responsive polypyrrole nanotubes using Ce(III)-stabilized maghemite nanoparticles.

Nanocomposites (NCs) that are made magnetically responsive in controlled conditions attract continuing interest for their added magnetic properties. In this study, we report on the preparation and full characterization of a multifunctional NC composed of magnetic γ-Fe(2)O(3) nanoparticles (NPs) covalently attached to the surface of polyaminated (polyNH(2)) poly(2,6-di-pyrrol-1-yl-hexanoic acid) (pDPL) nanotubes (NTs). Such a hybrid conducting polymer iron oxide maghemite γ-Fe(2)O(3)@pDPL NC built specifically on covalent bonding has never been reported. The maghemite γ-Fe(2)O(3) NPs were prepared using an innovative ultrasound-assisted Ce(3+) doping process, resulting in polycarboxylation of the NP surface useful for control of aggregation and derivatization of functionality. The second component of the NC, i.e. polyNH(2)-modified pDPL NTs, was prepared from an acid functional pyrrole species followed by amine modification. The resulting innovative γ-Fe(2)O(3)@pDPL NC can be viewed as a multifunctional nanomaterial since it possesses both types of derivatization, i.e. polyCOOH (NPs) and polyNH(2) (NTs) combined with magnetic responsivity.

Iterative optical technique for detecting anti-leishmania nanoparticles in mouse lesions.

Nanoparticles (NPs) based drugs for topical administration are gaining interest in the biomedical world. However, a study tool of their penetration depth to the different tissue layers without additional markers or contrast agents is required in order to relieve safety concerns. While common diagnostic tools, e.g. X-ray, computed tomography or magnetic resonance imaging, can provide in vivo detection of the metallic NPs, their resolution cannot determine the exact penetration depth to the thin skin layers. In this work, we propose the noninvasive nanophotonics iterative multi-plane optical property extraction (IMOPE) technique for the novel iron-based NPs detection in leishmaniasis lesions. The optical properties of the different tissue layers: epidermis, dermis, subcutaneous fat and muscle, were examined before and after topical drug administration. The potential topical drug was detected in the epidermis (∼13µm) and dermis (∼160µm) layers in mice lesions at different stages of the disease (two or four weeks post infection). The lesion size influence on the detection was also observed, where in larger lesions the IMOPE senses a greater presence of the topical drug.

The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection 'dead end'.

Innovative functional polymerization of pyrrole-N-propionic acid onto WS2 nanotubes using cerium-doped maghemite nanoparticles for photothermal therapy.

Tungsten disulfide nanotubes (WS2-NTs) were found to be very active for photothermal therapy. However, their lack of stability in aqueous solutions inhibits their use in many applications, especially in biomedicine. Few attempts were made to chemically functionalize the surface of the NTs to improve their dispersability. Here, we present a new polymerization method using cerium-doped maghemite nanoparticles (CM-NPs) as magnetic nanosized linkers between the WS2-NT surface and pyrrole-N-propionic acid monomers, which allow in situ polymerization onto the composite surface. This unique composite is magnetic, and contains two active entities for photothermal therapy-WS2 and the polypyrrole. The photothermal activity of the composite was tested at a wavelength of 808 nm, and significant thermal activity was observed. Moreover, the polycarboxylated polymeric coating of the NTs enables effective linkage of additional molecules or drugs via covalent bonding. In addition, a new method was established for large-scale synthesis of CM-NPs and WS2-NT-CM composites.

Nano-Leish-IL: A novel iron oxide-based nanocomposite drug platform for effective treatment of cutaneous leishmaniasis.

Kinetoplastids are infamous parasites that include trypanosomes and Leishmania species. Here, we developed an anti-Leishmania nano-drug using ultra-small functional maghemite (γ-Fe2O3) nanoparticles (NPs) that were surface-doped by [CeLn]3/4+ to enable effective binding of the polycationic polyethylenebyimine (PEI) polymer by coordinative chemistry. This resulting nano-drug is cytolytic in-vitro to both Trypanosoma brucei parasites, the causative agent of sleeping sickness, as well as to three Leishmania species. The nano-drug induces the rupture of the single lysosome present in these parasites attributed to the PEI, leading to cytolysis. To evaluate the efficacy of a "cream-based" version of the nano-drug, which was termed "Nano-Leish-IL" for topical treatment of cutaneous leishmaniasis (CL), we developed a rapid screening method utilizing T. brucei parasites involved in social motility and demonstrated that functional NPs arrested the migration of the parasites. This assay presents a surrogate system to rapidly examine the efficacy of "cream-based" drugs in topical preparations against leishmaniasis, and possibly other dermal infectious diseases. The resulting Nano-Leish-IL topical preparation eliminated L. major infection in mice. Thus, this study presents a novel efficient nano-drug targeting the single lysosome of kinetoplastid parasites.

Aggregation control of hydrophilic maghemite (gamma-Fe2O3) nanoparticles by surface doping using cerium atoms.

The high-power ultrasonic irradiation of preformed magnetite (Fe(3)O(4)) nanoparticles in the presence of monoelectronic Ce-containing ceric ammonium nitrate [Ce(IV)(NH(4))(2)(NO(3))(6)] oxidant in MeCOMe afforded hydrophilic 50 nm-sized colloidal, highly stable maghemite (gamma-Fe(2)O(3)) nanoparticles. An "inorganic" Ce atom doping of the NP surface has been proposed in order to rationalize the observed nanoparticle antiaggregation phenomenon. Quite importantly, this method did not require the use of any organic ligand and/or polymer for the passivation of the nanoparticle surface.

Functionalized tungsten disulfide nanotubes for dopamine and catechol detection in a tyrosinase-based amperometric biosensor design.

WS2 nanotubes functionalized with carboxylic acid functions (WS2-COOH) were used for improved immobilization of the enzyme tyrosinase in order to form an electrochemical biosensor towards catechol and dopamine. The nanotubes were deposited on glassy carbon electrodes using a dispersion-filtration-transfer procedure to assure the reproducibility of the deposits. After the electrochemical and morphological characterization of these WS2-COOH nanotube deposits, the formed biosensors showed very satisfying performance towards catechol detection with a linear range of 0.6-70 µmol L-1 and a sensitivity of 10.7 ± 0.2 mA L mol-1. The apparent Michaelis Menten constant of this system is slightly lower than the KM value of tyrosinase in solution, reflecting an excellent accessibility of the active site of the enzyme combined with a good mass transport of the target molecule through the deposit. For dopamine detection, we observed an accumulation of this substrate due to electrostatic interactions between the amine function of dopamine and the carboxylic acid groups of the nanotubes. This led to improved signal capture at low dopamine concentrations. With linear ranges of 0.5-10 µmol L-1 and 10-40 µmol L-1, and respective sensitivities of 6.2 ± 0.7 mA L mol-1 and 3.4 ± 0.4 mA L mol-1, the overall sensor performance is within the average of comparable results using carbon nanotubes. Nonetheless, the simplified handling of these nanotubes and their reduced environmental impact make these WS2-COOH nanotubes a promising nanomaterial for biosensing applications.