Citrate-stabilized Nanoparticles Research Articles

Development of Thermo- and pH-Sensitive Liposomal Magnetic Carriers for New Potential Antitumor Thienopyridine Derivatives.

The development of stimuli-sensitive drug delivery systems is a very attractive area of current research in cancer therapy. The deep knowledge on the microenvironment of tumors has supported the progress of nanosystems’ ability for controlled and local fusion as well as drug release. Temperature and pH are two of the most promising triggers in the development of sensitive formulations to improve the efficacy of anticancer agents. Herein, magnetic liposomes with fusogenic sensitivity to pH and temperature were developed aiming at dual cancer therapy (by chemotherapy and magnetic hyperthermia). Magnetic nanoparticles of mixed calcium/manganese ferrite were synthesized by co-precipitation with citrate and by sol–gel method, and characterized by X-ray diffraction (XRD), scanning electron microscopy in transmission mode (STEM), and superconducting quantum interference device (SQUID). The citrate-stabilized nanoparticles showed a small-sized population (around 8 nm, determined by XRD) and suitable magnetic properties, with a low coercivity and high saturation magnetization (~54 emu/g). The nanoparticles were incorporated into liposomes of dipalmitoylphosphatidylcholine/cholesteryl hemisuccinate (DPPC:CHEMS) and of the same components with a PEGylated lipid (DPPC:CHEMS:DSPE-PEG), resulting in magnetoliposomes with sizes around 100 nm. Dynamic light scattering (DLS) and electrophoretic light scattering (ELS) measurements were performed to investigate the pH-sensitivity of the magnetoliposomes’ fusogenic ability. Two new antitumor thienopyridine derivatives were efficiently encapsulated in the magnetic liposomes and the drug delivery capability of the loaded nanosystems was evaluated, under different pH and temperature conditions.

Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release.

Currently, the nanoparticle functionalization effect on supramolecular peptide-based hydrogels remains undescribed, but is expected to affect the hydrogels’ self-assembly and final magnetic gel properties. Herein, two different functionalized nanoparticles: citrate-stabilized (14.4 ± 2.6 nm) and lipid-coated (8.9 ± 2.1 nm) magnetic nanoparticles, were used for the formation of dehydropeptide-based supramolecular magnetogels consisting of the ultra-short hydrogelator Cbz-L-Met-Z-ΔPhe-OH, with an assessment of their effect over gel properties. The lipid-coated nanoparticles were distributed along the hydrogel fibers, while citrate-stabilized nanoparticles were aggregated upon gelation, which resulted into a heating efficiency improvement and decrease, respectively. Further, the lipid-coated nanoparticles did not affect drug encapsulation and displayed improved drug release reproducibility compared to citrate-stabilized nanoparticles, despite the latter attaining a stronger AMF-trigger. This report points out that adsorption of nanoparticles to hydrogel fibers, which display domains that improve or do not affect drug encapsulation, can be explored as a means to optimize the development of supramolecular magnetogels to advance theranostic applications.

Understanding prodrugs: complexation in aqueous solutions of doxorubicin, bovine serum albumin and gold nanoparticles

Aqueous solutions of doxorubicin (DOX), doxorubicin with bovine serum albumin (DOX-BSA), and DOX-BSA in solutions containing gold nanoparticles (AuNPs) with different concentrations of each system component are studied for the first time. The study of the concentration and time-resolved dependences of optical density spectra indicates that the interaction of protonated molecules of the antibiotic with the citrate-covered surface of the nanoparticles of high concentration promotes the aggregation and precipitation of AuNPs. On the other hand, protein macromolecules effectively form conjugates with nanoparticles, preventing their aggregation. Competition of these processes significantly complicates the behavior of optical density spectra at the absorption band of doxorubicin. The simultaneous processes of AuNP aggregation and BSA-AuNP association allow reasonable result of calculation of equilibrium-binding constants for the DOX-BSA complexation process to be obtained only at low nanoparticle concentrations (up to 1.3 × 10−10 M). It was found that these constants decrease to K = 1.18 × 106 M−1 compared with K = 4.74 × 106 M−1 for the DOX-BSA complex, indicating lower stability of these complexes after citrate-stabilized nanoparticles addition. The number of binding sites in DOX-BSA complexes, as shown by the analysis of the isomolar series curves, stays the same for the indicated AuNPs concentrations and is equal to n = 2. The obtained results could be useful to clarify the appropriate concentration of such type of AuNPs upon the development of oncology prodrugs.

Magnetic detection of nanoparticle sedimentation in magnetized ferrofluids

Colloidal stability in external magnetic field is crucial for applications of ferrofluids. Here, we introduce a magnetic analysis approach to monitor how rapidly magnetic nanoparticles are pulled out of the liquid in an external magnetic field gradient. The motion of the sedimentation front is deduced from the time-dependent field produced by a column of ferrofluid placed on a permanent magnet. Citrate-stabilized nanoparticles in a homemade aqueous ferrofluid are found to sediment at the rate expected of single nanoparticles. More rapid sedimentation occurs in two other types of ferrofluid, indicating that our magnetic sedimentation analysis method can differentiate ferrofluids with respect to their in-field colloidal stability. Our method is further validated by comparison with time-dependent X-ray transmission profiles.

Internalization capabilities of gold-198 nanoparticles: Comparative evaluation of effects of chitosan agent on cellular uptake into MCF-7

In this study, internalization of positively charged chitosan-coated nanoparticles (198AuNPs@chitosan) on MCF-7 cells was investigated by γ-ray spectroscopy and then statistically compared to that of 198Au and negatively charged citrate-stabilized nanoparticles (198AuNPs). Sub-50 nm 198AuNPs@chitosan had a higher internalization compared to 198Au and 198AuNPs (p < 0.05). More cellular uptake of 198AuNP@chitosan means a higher dose of radioactivity to the tumor cells which, in turn, more effective treatment of the cancer.

Facile synthesis of gold nanoparticles capped with an ammonium-based chiral ionic liquid crystal

ABSTRACTHerein, we describe a facile synthesis of stable chiral ionic liquid crystal (ILC)-capped gold nanoparticles. A new ILC containing a chiral cholesterol moiety having a terminal triethylammonium group was synthesised which exhibited an enantiotropic lamellar mesophase. Stable, monodisperse citrate-stabilised gold nanoparticles having a size of ~60 nm were prepared and the citrate ligands on the gold nanoparticles were replaced with chiral ILC through a two-phase ligand exchange process. The resulting chiral ILC-stabilised particles were characterised using UV–visible (UV–Vis) and transmission electron microscopy (TEM) studies. Different from the citrate-stabilised nanoparticles, the ligand exchanged gold nanoparticles were dispersible in organic solvent and resulting dispersion was stable for more than observed period of 3 months. Furthermore, the chiral ILC-decorated gold nanoparticles were found to be well dispersible in a nematic host without any aggregation and induced a vertical alignment of the nematic director.

Lysosomal responses to different gold forms (nanoparticles, aqueous, bulk) in mussel digestive cells: a trade-off between the toxicity of the capping agent and form, size and exposure concentration

Gold nanoparticles (NPs) are increasingly used in technological materials and consumer products and may have toxicological characteristics distinct from bulk and aqueous gold. The aim of this work was to understand the effects of Au NPs especially, how the form, the size and the coating influence bioaccumulation/biodistribution and toxicity of NPs in mussels, Mytilus galloprovincialis. Mussels were exposed for 3 d to concentrations of Au (0.75, 75 and 750 μg Au/l) supplied as Au-Cit NPs (5 and 40 nm; Au5-Cit and Au40-Cit), bulk and aqueous Au (HAu(III)Cl4), and to the capping agent (Na-citrate) in doses used in the formulation of NPs (0.005, 0.5, 5 mg/l). Citrate-stabilised NPs formed stable suspensions of aggregates in seawater (SW) available for mussels. Au accumulation in soft tissues was similar in Au40-Cit and aqueous Au exposed mussels, lower in Au5-Cit and negligible after bulk exposure. Au NPs were identified (X-ray microanalysis) in different compartments of the endolysosomal system in digestive cells, and small size NPs (5 nm) were more accumulated than 40 nm NPs, aqueous and bulk. The degree of lysosomal membrane destabilisation was related with intralysosomal metal accumulation and depended on the form, NP size (Au5-Cit > Au40-Cit > aqueous > bulk) and concentration. Citrate alone provoked extreme reduction in lysosomal membrane stability. Toxicopathic alterations were recorded in digestive gland cells (vacuolisation, swollen RER, connective tissue disruption and cell death) especially in mussels exposed to 40 nm NPs. Deleterious effects resulted from digestive tract obliteration (agglomerates) and digestion malfunction. The toxic effect of Au-Cit NPs was influenced both by NP size, capping agent composition and the dose of capping agent carried by NPs, which was size dependent.

Toxicity of silver nanoparticles towards tumoral human cell lines U-937 and HL-60

The toxicity of three types of silver nanoparticles towards histiocytic lymphoma (U-937) and human promyelocytic cells (HL-60) was studied. The nanoparticles were synthesized in a chemical reduction method using sodium borohydride. Trisodium citrate and cysteamine hydrochloride were used to generate a negative and positive nanoparticle surface charge. The evaluation of cell viability, membrane integrity, antioxidant activity and the induction of inflammation were used to evaluate the difference in cellular response to the nanoparticle treatment. The results revealed that the cysteamine-stabilized (positively charged) nanoparticles (SBATE) were the least toxic although they exhibited a similar ion release profile as the unmodified (negatively charged) nanoparticles obtained using sodium borohydride (SBNM). Citrate-stabilized nanoparticles (SBTC) induced superoxide dismutase (SOD) activity in the HL-60 cells and total antioxidant activity in the U-937 cells despite their resistance to oxidative dissolution. The toxicity of SBNM nanoparticles was manifested in the disruption of membrane integrity, decrease in the mitochondrial functions of cells and the induction of inflammation. These findings allowed to conclude that mechanism of silver nanoparticle cytotoxicity is the combination of effects coming from the surface charge of nanoparticles, released silver ions and biological activity of stabilizing agent molecules.

Singlet Oxygen Generation by Laser Irradiation of Gold Nanoparticles.

The formation of singlet oxygen by irradiation of gold nanoparticles in their plasmon resonance band with continuous or pulsed laser light has been investigated. Citrate-stabilized nanoparticles were found to facilitate the photogeneration of singlet oxygen, albeit with low quantum yield. The reaction caused by pulsed laser irradiation makes use of the equilibrated hot electrons that can reach temperatures of several thousand degrees during the laser pulse. Although less efficient, continuous irradiation, which acts via the short-lived directly excited primary “hot” electrons only, can produce enough singlet oxygen for photodynamic cancer therapy and has significant advantages for practical applications. However, careful design of the nanoparticles is needed, since even a moderately thick capping layer can completely inhibit singlet oxygen formation. Moreover, the efficiency of the process also depends on the nanoparticle size.

The Morphological Changes in the Internal Organs in Tumor-Bearing Rats at Intravenous Injection of Citrate-Stabilized Magnetite Nanoparticles

The usefulness of magnetite nanoparticles to improve contrast in magnetic resonance imaging (MRI) of tumor visualization was actively investigated currently. In this work, we conducted MRI and morphological examination of internal organs of 30 white outbred rats with transplanted liver tumor PC-1 after intravenous administration of magnetite hydrosols. Intravenous administration of citrate-stabilized magnetite nanoparticles in a dosage of 20 μg/kg and 16 mg/kg resulted in a disruption of blood filling of the organs, mainly due to the plethora. The dystrophic cell damage was observed in liver and in kidneys. The activation of immune processes in spleen was fixed after intravenous administration of citrate stabilized magnetite nanoparticles. In both doses, the nanoparticles were founded in the heart and brain, but the significant iron accumulation was detected in the tumor by methods of MRI and atomic absorption spectroscopy (AAS) only in dosage of 16 mg/kg. It is possible to conclude that selected dosage is sufficient for accumulation of nanoparticles in tumor, but it does not cause significant changes in the internal organs.

Assembly of metal nanoparticles on regenerated fibers from wood sawdust and de-inked pulp: flexible substrates for surface enhanced Raman scattering (SERS) applications

We report on simple and low-cost active SERS substrates made using regenerated fibers from wood products. Glycidyltrimethylammonium chloride (GTAC) was used to graft ammonium groups on the fibers’ surfaces under strong alkaline conditions. After GTAC treatment, citrate-stabilized nanoparticles were assembled via electrostatic interaction. X-ray diffraction, Scanning electron microscopy images and optical photographs indicated that the surfaces of the fibers were conformally coated with metal nanoparticles. We also observed that after being cationized, the fibers experienced significant swelling and shrinking under dry and wet conditions. Rhodamine 6G was used as probe molecule to test the SERS performance of the substrates- concentrations as low as 10−9 M were detected. Furthermore, the modified fibers were used to detect melamine, illustrating their potential as viable substrates for applications such as markers for the quality and shelf-life of food products and detection of toxins.

Multimetallic Complexes and Functionalized Gold Nanoparticles Based on a Combination of d- and f-Elements

The new DO3A-derived dithiocarbamate ligand, DO3A-(t)Bu-CS2K, is formed by treatment of the ammonium salt [DO3A-(t)Bu]HBr with K2CO3 and carbon disulfide. DO3A-(t)Bu-CS2K reacts with the ruthenium complexes cis-[RuCl2(dppm)2] and [Ru(CH═CHC6H4Me-4)Cl(CO)(BTD)(PPh3)2] (BTD = 2,1,3-benzothiadiazole) to yield [Ru(S2C-DO3A-(t)Bu)(dppm)2](+) and [Ru(CH═CHC6H4Me-4)(S2C-DO3A-(t)Bu)(CO)(PPh3)2], respectively. Similarly, the group 10 metal complexes [Pd(C,N-C6H4CH2NMe2)Cl]2 and [PtCl2(PPh3)2] form the dithiocarbamate compounds, [Pd(C,N-C6H4CH2NMe2)(S2C-DO3A-(t)Bu)] and [Pt(S2C-DO3A-(t)Bu)(PPh3)2](+), under the same conditions. The linear gold complexes [Au(S2C-DO3A-(t)Bu)(PR3)] are formed by reaction of [AuCl(PR3)] (R = Ph, Cy) with DO3A-(t)Bu-CS2K. However, on reaction with [AuCl(tht)] (tht = tetrahydrothiophene), the homoleptic digold complex [Au(S2C-DO3A-(t)Bu)]2 is formed. Further homoleptic examples, [M(S2C-DO3A-(t)Bu)2] (M = Ni, Cu) and [Co(S2C-DO3A-(t)Bu)3], are formed from treatment of NiCl2·6H2O, Cu(OAc)2, or Co(OAc)2, respectively, with DO3A-(t)Bu-CS2K. The molecular structure of [Ni(S2C-DO3A-(t)Bu)2] was determined crystallographically. The tert-butyl ester protecting groups of [M(S2C-DO3A-(t)Bu)2] (M = Ni, Cu) and [Co(S2C-DO3A-(t)Bu)3] are cleaved by trifluoroacetic acid to afford the carboxylic acid products, [M(S2C-DO3A)2] (M = Ni, Cu) and [Co(S2C-DO3A)3]. Complexation with Gd(III) salts yields trimetallic [M(S2C-DO3A-Gd)2] (M = Ni, Cu) and tetrametallic [Co(S2C-DO3A-Gd)3], with r(1) values of 11.5 (Co) and 11.0 (Cu) mM(-1) s(-1) per Gd center. DO3A-(t)Bu-CS2K can also be used to prepare gold nanoparticles, Au@S2C-DO3A-(t)Bu, by displacement of the surface units from citrate-stabilized nanoparticles. This material can be transformed into the carboxylic acid derivative Au@S2C-DO3A by treatment with trifluoroacetic acid. Complexation with Gd(OTf)3 or GdCl3 affords Au@S2C-DO3A-Gd with an r(1) value of 4.7 mM(-1) s(-1) per chelate and 1500 mM(-1) s(-1) per object.

Photoluminescence of cerium fluoride and cerium-doped lanthanum fluoride nanoparticles and investigation of energy transfer to photosensitizer molecules.

CexLa1-xF3 nanoparticles have been proposed for use in nanoscintillator-photosensitizer systems, where excitation of nanoparticles by ionizing radiation would result in energy transfer to photosensitizer molecules, effectively combining the effects of radiotherapy and photodynamic therapy. Thus far, there have been few experimental investigations of such systems. This study reports novel synthesis methods for water-dispersible Ce0.1La0.9F3/LaF3 and CeF3/LaF3 core/shell nanoparticles and an investigation of energy transfer to photosensitizers. Unbound deuteroporphyrin IX 2,4-disulfonic acid was found to substantially quench the luminescence of large (>10 nm diameter) aminocaproic acid-stabilized nanoparticles at reasonable concentrations and loading amounts: up to 80% quenching at 6% w/w photosensitizer loading. Energy transfer was found to occur primarily through a cascade, with excitation of "regular" site Ce(3+) at 252 nm relayed to photosensitizer molecules at the nanoparticle surface through intermediate "perturbed" Ce(3+) sites. Smaller (<5 nm) citrate-stabilized nanoparticles were coated with the bisphosphonate alendronate, allowing covalent conjugation to chlorin e6 and resulting in static quenching of the nanoparticle luminescence: ∼50% at ∼0.44% w/w. These results provide insight into energy transfer mechanisms that may prove valuable for optimizing similar systems.

Quantitative Evaluation of Cellular Uptake and Trafficking of Plain and Polyethylene Glycol‐Coated Gold Nanoparticles

This study addresses the cellular uptake and intracellular trafficking of 15-nm gold nanoparticles (NPs), either plain (i.e., stabilized with citrate) or coated with polyethylene glycol (PEG), exposed to human alveolar epithelial cells (A549) at the air-liquid interface for 1, 4, and 24 h. Quantitative analysis by stereology on transmission electron microscopy images reveals a significant, nonrandom intracellular distribution for both NP types. No particles are observed in the nucleus, mitochondria, endoplasmic reticulum, or golgi. The cytosol is not a preferred cellular compartment for both NP types, although significantly more PEG-coated than citrate-stabilized NPs are present there. The preferred particle localizations are vesicles of different sizes (<150, 150-1000, >1000 nm). This is observed for both NP types and indicates a predominant uptake by endocytosis. Subsequent inhibition of caveolin- and clathrin-mediated endocytosis by methyl-beta-cyclodextrin (MbetaCD) results in a significant reduction of intracellular NPs. The inhibition, however, is more pronounced for PEG-coated than citrate-stabilized NPs. The latter are mostly found in larger vesicles; therefore, they are potentially taken up by macropinocytosis, which is not inhibited by MbetaCD. With prolonged exposure times, both NPs are preferentially localized in larger-sized intracellular vesicles such as lysosomes, thus indicating intracellular particle trafficking. This quantitative evaluation reveals that NP surface coatings modulate endocytotic uptake pathways and cellular NP trafficking. Other nonendocytotic entry mechanisms are found to be involved as well, as indicated by localization of a minority of PEG-coated NPs in the cytosol.

Gold Sols as Catalysts for Glycerol Oxidation: The Role of Stabilizer

AbstractGold nanoparticles (Au NPs), stabilized by polyvinylalcohol (PVA), tetrakishydroxypropylphosphonium chloride (THPC), and citrate, have been synthesized and tested in the liquid‐phase oxidation of glycerol. THPC‐stabilized Au NPs have been found to exhibit remarkable catalytic activity (TOF=2478 h−1) in comparison to PVA‐ and citrate‐stabilized nanoparticles (TOF=715 and 160 h−1, respectively). The catalytic results can be explained in terms of particle size but aging treatment also revealed the influence of the protective agent. PVA as stabilizer produced small and quite stable gold nanoparticles differently from the THPC system. However PVA also limits the accessibility of reactant to the active site.

In-Situ Measurement of Colloidal Gold Adsorption on Functionalized Silica Surfaces

Evanescent wave cavity ring-down spectroscopy (EW-CRDS) has been applied to study, in situ, the deposition kinetics of commercially available gold colloids on functionalized silica surfaces from quiescent solution. Neither 5 nor 20 nm citrate-stabilized nanoparticles were observed to adsorb on clean silica surfaces. Adsorption on a poly-l-lysine-functionalized surface, however, occurs readily and irreversibly with the kinetics of adsorption differing markedly for the two particle sizes studied. 5 nm particles adsorb to form a highly disperse submonolayer of individual particles with atomic force microscope images showing no evidence of aggregation. The controlled growth of multilayer nanoparticle/polyelectrolyte films is demonstrated by alternately depositing colloidal particles and poly-l-lysine films. The deposition of multilayer nanoparticle films increases the sensitivity of the functionalized surface to changes in the solvent refractive index. The adsorption kinetics of the 20 nm colloid is more complex than that of the smaller colloid with adsorbed particles acting as nucleation sites for subsequent aggregation with the result that the interfacial absorbance continues to increase indefinitely with time.

Analysis of doped luminescent lanthanide fluoride nanoparticles by low gas flow inductively coupled plasma optical emission spectrometry

Low-flow inductively coupled plasma optical emission spectrometry is applied for the analysis of water-soluble LaF3nanocrystals doped with different lanthanide ions (Ce3+, Eu3+, Ho3+, Tb3+) for the first time. Colloidal solutions of citrate-stabilized nanoparticles (mean size 24 nm) were directly introduced into the plasma and no significant differences to digested particles were observed. The low-flow approach reduced the argon consumption of conventional instrumentation by 95% and provided limits of detection (LOD) for rare earth elements in the low microgram-per-liter range (Eu: 0.08 µg L−1, Ho: 0.18 µg L−1, La: 0.36 µg L−1, Tb: 0.56 µg L−1, Ce: 3.14 µg L−1). Relative standard deviations (RSDs) in the range of 1–2.2% with pneumatic sample introduction were obtained. The analytical performance of the low-flow torch was assessed by direct comparison with a conventional torch. Recoveries in the range of 97–104% were observed for most elements.

Stable Aqueous Nanoparticle Film Assemblies with Covalent and Charged Polymer Linking Networks

The construction of highly stable and efficiently assembled multilayer films of purely water soluble gold nanoparticles is reported. Citrate-stabilized nanoparticles (CS-NPs) of average core diameter of 10 nm are used as templates for stabilization-based exchange reactions with thioctic acid to form more robust aqueous NPs that can be assembled into multilayer films. The thioctic acid stabilized nanoparticles (TAS-NPs) are networked via covalent and electrostatic linking systems, employing dithiols and the cationic polymer poly(L-lysine), respectively. Multilayer films of up to 150 nm in thickness are successfully grown at biological pH with no observable degradation of the NPs within the film. The characteristic surface plasmon band, an optical feature of certain NP film assemblies that can be used to report the local environment and core spacing within the film, is preserved. Growth dynamics and film stability in solution and in the air are examined, with poly(L-lysine) linked films showing no evidence of aggregation for at least 50 days. We believe these films represent a pivotal step toward exploring the potential of aqueous NP film assemblies as a sensing apparatus.

Extinction coefficient of gold nanoparticles with different sizes and different capping ligands

Extinction coefficients of gold nanoparticles with core size ranging from ∼4 to 40 nm were determined by high resolution transmission electron microscopy analysis and UV–vis absorption spectroscopic measurement. Three different types of gold nanoparticles were prepared and studied: citrate-stabilized nanoparticles in five different sizes; oleylamide-protected gold nanoparticles with a core diameter of 8 nm, and a decanethiol-protected nanoparticle with a diameter of around 4 nm. A linear relationship between the logarithms of extinction coefficients and core diameters of gold particles was found independent of the capping ligands on the particle surface and the solvents used to dissolve the nanoparticles. This linear relation may be used as a calibration curve to determine the concentration or average size of an unknown nanoparticle or nanoparticle–biomolecule conjugate sample.