Dendrimer-stabilized Gold Nanoparticles Research Articles

A Dendrimer-Based Dual Radiodense Element-Containing Nanoplatform for Targeted Enhanced Tumor Computed Tomography Imaging.

The exploration of original computed tomography (CT) imaging contrast agents with enhanced sensitivity and specificity is currently one of the major challenging tasks for precision medicine. Herein, we develop an innovative nanoprobe of dendrimer-stabilized gold nanoparticles (Au DSNs) linked with folic acid (FA) as a targeting ligand and diatrizoic acid (DTA) for specific enhanced tumor CT imaging. In current work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) with amine termini were adopted to entrap Au NPs through a stepwise complexation/reduction method to achieve a higher Au loading than the conventional one-step complexation/reduction method. The prepared [(Au0)120-G5.NH2] NPs were sequentially functionalized with diatrizoic acid (DTA), a typical CT contrast agent based on iodine(I), FA through a poly(ethylene glycol) (PEG) spacer, and carboxylated PEG monomethyl ether (mPEG-COOH), ended with complete acetylation of the leftover dendrimer amine termini. The generated Au DSNs-DTA-FA (Au core diameter = 5.9 nm) were thoroughly characterized. Our data reveal that the Au DSNs-DTA-FA containing Au and I dual radiodense elements are stable, display enhanced CT imaging performance, much higher than the single-radiodense elemental material solely based on Au or I, and possess a quite good cytocompatibility. With the demonstrated FA-rendered specific targeting, the developed Au DSNs-DTA-FA can be employed as a highly efficient nanoprobe for targeted enhanced CT imaging of cancer cells and a subcutaneous tumor model. Overall, the created Au DSNs-DTA-FA may be a powerful nanoprobe for specific enhanced CT imaging of various kinds of FA receptor-expressing tumors or biosystems.

Dendrimer-Capped Gold Nanoparticles for Highly Reliable and Robust Surface Enhanced Raman Scattering.

Dendrimer-stabilized gold nanoparticles (Au-Den) were prepared by a facile solution based method for a highly reliable and robust surface enhanced Raman scattering (SERS) substrate. Au-Den was selectively attached on the surface of reduced graphene oxide (rGO) by noncovalent interactions between the Au capping dendrimer and the graphene surface. Au-Den/rGO exhibits the outstandingly stable and highly magnified Raman signal with an enhancement factor (EF) of 3.9 × 10(7) that enables detection of R6G dyes with concentration as low as 10 nM, retaining 95% of the Raman signal intensity after 1 year. The remarkable stability and enhancement originated not only from a simple combination of the electromagnetic and chemical mechanism of SERS but also from intensified packing density of stable Au-Den on the graphene substrate due to the firm binding between the dendrimer capped metal nanoparticles and the graphene substrate. This method is not limited to the gold nanoparticles and G4 dendrimer used herein, but also can be applied to other dendrimers and metal nanoparticles, which makes the material platform suggested here superior to other SERS substrates.

The assembly of dendrimer-stabilized gold nanoparticles onto electrospun polymer nanofibers for catalytic applications

We report here a facile approach to assembling low generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) onto electrospun polymer nanofibrous mats for catalytic applications. In this study, Au DSNPs formed using amine-terminated generation 2 PAMAM dendrimers as stabilizers were assembled onto electrospun polyacrylic acid (PAA)/polyvinyl alcohol (PVA) nanofibrous mats either through electrostatic interactions or through the covalent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) coupling reaction. The assembly of Au DSNPs with a mean diameter of 5.4 nm onto the electrospun nanofibrous mats was characterized via different techniques. The catalytic activity of the Au DSNP-assembled nanofibrous mats was evaluated by the transformation of 4-nitrophenol to 4-aminophenol. We show that both approaches enable the efficient assembly of Au DSNPs onto nanofiber surfaces and the as prepared Au DSNP-containing nanofibers formed via both approaches have excellent catalytic activity and reusability. However, the Au DSNP-assembled nanofibers via electrostatic physical interactions display a much higher catalytic activity than those formed via the chemical assembly approach. The facile dendrimer-mediated assembly approach to modifying electrospun nanofibers may be used to fabricate other composite nanofiber systems for applications in catalysis, sensing, and biomedical sciences.

Targeted dendrimer-stabilized gold nanoparticles for computed tomography imaging of cancer cells

There has been extensive research on drug delivery from biodegradable polymeric devices. Biodegradable polymers were widely and successfully used for tissue engineering because of their biocompatibility, biodegradability,metabolizability, low toxicity and so on. In the past decade, significant effort has been directed to the development of coaxial electrospun nanofibers for treatment of disease with binary release control. Up to now just two different growth factors were physically and chemically loaded into a single nanofibrous matrix [1]. Here, we report a system in which a mixture of poly (vinyl pyrrolidone) (PVP) and nanosilver was used as the shell and PLLA with a model drug as the core. Nanosilver particles (NSPs) were rapidly synthesized from AgNO3 aqueous solutions containing PVP via microwave irradiation. The mass ratio of AgNO3 and PVP was 1:5. AgNO3 solutions were preheated for 3 min via microwave irradiation. PVP/NSP composites were prepared by electrospinning of 10 wt.% PVP solutions that contained NSPs in water (Scheme 1). Therefore, these composites could be applied as tissue engineering and antimicrobial materials [2]. PLLA (polylactic acid) and model drug were mixed and agitated overnight on a magnetic stirrer at room temperature. The solvent was a mixture of dimethyl formamide and acetone (2:1, v/v). In vitro release and antimicrobial tests showed that the binary-drug loaded fibermats not only were antimicrobial, but also released a model drug in an ideal way for 6 days.

Targeted Tumor Computed Tomography Imaging Using Low‐Generation Dendrimer‐Stabilized Gold Nanoparticles

We report a facile approach to fabricating low-generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine-terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA-modified Au DSNPs are stable at different pH values (5-8) and temperatures (4-50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA-modified Au DSNPs are noncytotoxic in the particle concentration range of 0-3000 nM. X-ray attenuation coefficient measurements show that the CT value of FA-modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA-modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over-expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X-ray attenuation coefficient, the FA-modified low-generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over-expressing FA receptors.

Constructing Metal Nanoparticle Multilayers with Polyphenylene Dendrimer/Gold Nanoparticles via “Click” Chemistry

Multilayer films composed of azide-functional polymer and polyphenylene dendrimer-stabilized gold nanoparticles with alkynes in their peripheries have been fabricated using a layer-by-layer (LBL) approach via "click" chemistry. This method permits facile covalent linking of the polymer/nanoparticle interlayers in the mixture of DMF and water, which provides a general and powerful technique for preparing uniform nanoparticle (NP) thin films. The deposition process is linearly related to the number of bilayers as monitored by UV-vis spectroscopy. The multilayer structure and morphology have been characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and contact angle.

Facile hydrothermal synthesis of low generation dendrimer-stabilized gold nanoparticles for in vivo computed tomography imaging applications

We report a facile approach to synthesizing low generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) for in vivo computed tomography (CT) imaging applications. In this study, amine-terminated generation 2 PAMAM dendrimers were employed as stabilizers to form gold nanoparticles via a simple hydrothermal method. The formed aminated Au DSNPs were then acetylated to neutralize the dendrimer terminal amines, rendering the particles with improved biocompatibility. The final formed acetylated Au DSNPs were characterized via different techniques. We show that the formed Au DSNPs with an Au core size of 5.6 nm are relatively uniform and stable at different pH (5–8) and temperature (4–50 °C) conditions. X-ray attenuation coefficient measurements show that the Au DSNPs display approximately the same X-ray attenuation property as that of Omnipaque, a clinically used iodinated contrast agent. Importantly, the acetylated Au DSNPs showed much better performance in CT imaging of the major organs of rats (heart, liver, kidney, spleen, and bladder) in vivo than Omnipaque, likely due to their nanometer size and thus prolonged blood circulation time. The formed Au DSNPs may be used as a promising contrast agent for CT imaging of different biological systems.

Layer-by-layer assembled multilayer films of reduced graphene oxide/gold nanoparticles for the electrochemical detection of dopamine

Graphene/gold nanoparticle multilayer films composed of polysodium 4-styrenesulfonate (PSS) functionalized reduced graphene oxide (RGO) and polyamidoamine (PAMAM) dendrimer stabilized gold nanoparticles (AuNPs) were built up using the electrostatic layer-by-layer (LBL) self-assembly technique on a glassy carbon electrode (GCE) modified with a first layer of poly(diallyldimethylammonium chloride) (PDDA). The film assembly, the electrochemical property as well as the electrocatalytic activity toward the oxidation of dopamine were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Electrochemical studies exhibit that the LBL assembled RGO/AuNPs films possess an excellent sensing performance for the detection of dopamine with a linear range from 1μM to 60μM and a limit of detection (LOD) as low as 0.02μM based on S/N=3. In addition, this electrochemical sensor was applied to the simultaneous detection of dopamine and uric acid by using DPV with high sensitivity and selectivity. The good analytical performance and long-term stability of the proposed sensor can be attributed to the combination of the reduced graphene oxide and gold nanoparticles in the LBL assembly films and the synergistic effect on the electrochemical oxidation of dopamine.

Facile formation of dendrimer-stabilized gold nanoparticles modified with diatrizoic acid for enhanced computed tomography imaging applications

We report a facile approach to forming dendrimer-stabilized gold nanoparticles (Au DSNPs) through the use of amine-terminated fifth-generation poly(amidoamine) (PAMAM) dendrimers modified by diatrizoic acid (G5.NH(2)-DTA) as stabilizers for enhanced computed tomography (CT) imaging applications. In this study, by simply mixing G5.NH(2)-DTA dendrimers with gold salt in aqueous solution at room temperature, dendrimer-entrapped gold nanoparticles (Au DENPs) with a mean core size of 2.5 nm were able to be spontaneously formed. Followed by an acetylation reaction to neutralize the dendrimer remaining terminal amines, Au DSNPs with a mean size of 6 nm were formed. The formed DTA-containing [(Au(0))(50)-G5.NHAc-DTA] DSNPs were characterized via different techniques. We show that the Au DSNPs are colloid stable in aqueous solution under different pH and temperature conditions. In vitro hemolytic assay, cytotoxicity assay, flow cytometry analysis, and cell morphology observation reveal that the formed Au DSNPs have good hemocompatibility and are non-cytotoxic at a concentration up to 3.0 μM. X-ray absorption coefficient measurements show that the DTA-containing Au DSNPs have enhanced attenuation intensity, much higher than that of [(Au(0))(50)-G5.NHAc] DENPs without DTA or Omnipaque at the same molar concentration of the active element (Au or iodine). The formed DTA-containing Au DSNPs can be used for CT imaging of cancer cells in vitro as well as for blood pool CT imaging of mice in vivo with significantly improved signal enhancement. With the two radiodense elements of Au and iodine incorporated within one particle, the formed DTA-containing Au DSNPs may be applicable for CT imaging of various biological systems with enhanced X-ray attenuation property and detection sensitivity.

Hydroxylated Dendrimer-Stabilized Gold and Silver Nanoparticles: Spontaneous Formation, Characterization, and Surface Properties

We present a general route to the facile and spontaneous synthesis of gold (Au) and silver (Ag) nanoparticles (NPs) through the use of hydroxylated poly(amidoamine) (PAMAM) dendrimers as both stabilizers and reducing agents. The formation of Au NPs can be achieved by simply mixing the generation 4 (G4) and 5 (G5) glycidol-modified PAMAM dendrimers with HAuCl4 in either methanol or water at room temperature. The size of the formed Au NPs can be varied through the change of dendrimer generations and reaction solvents. We also show that 1,2-epoxyhexane-modified G4 PAMAM dendrimers can be used as both stabilizers and reducing agents to form Au NPs, providing a useful approach to tuning the surface hydrophilicity of Au NPs. Furthermore, using the same strategy of spontaneous formation of Au NPs, Ag NPs can be readily formed through the use of glycidol hydroxyl-terminated G5 PAMAM dendrimers as both stabilizers and reducing agents. The facile synthesis of Au and Ag NPs using hydroxylated PAMAM dendrimers may offer many opportunities for their uses in a variety of applications. Keywords: Dendrimers, Gold nanoparticles, Silver nanoparticles, Hydroxylation, Stabilization

Encapsulation and Stabilization of Gold Nanoparticles with “Click” Polyethyleneglycol Dendrimers

Water-soluble arene-cored "clicked" and non-"clicked" dendrimers terminated by 27, 81, and 243 triethyleneglycol (TEG) tethers (respectively generations G0, G1, and G2) have been synthesized and shown to form dendrimer-encapsulated gold nanoparticles (DEAuNPs) and dendrimer-stabilized gold nanoparticles (DSAuNPs). The dendrimers have been characterized by IR, (1)H NMR, (13)C NMR, size-exclusion chromatography, elemental analysis, MALDI-TOF mass spectroscopy, DOSY NMR, and dynamic light scattering. The AuNPs have been generated and stabilized by these PEGylated dendrimers using a variety of reduction modes, including NaBH(4) in methanol, various single-electron metallocene-type reductants, and even in the absence of additional reductants. The active role of the "clicked" triazole rings, dendrimer generation, stoichiometry of Au precursor, and nature of the reductant and of the solvent are delineated, leading to DSAuNPs with the G0 dendrimer and smaller DEAuNPs with the G1 and G2 dendrimers. Altogether, AuNPs in the size range from 1.8 to 42 nm were formed and characterized by transmission electron microscopy (TEM), high resolution TEM (HRTEM) and UV-vis spectroscopy. Both 1,2,3-triazole and PEGylated Percec-type dendrons are required in the dendrimer structure for the stabilization of AuNPs upon NaBH(4) reduction of HAuCl(4) in methanol. On the other hand, in the absence of other reductant in water, only PEGylated Percec-type dendrons in dendrimers were found to be indispensable, because of their semicavitand shape, for the spontaneous reduction of HAuCl(4) and stabilization of DSAuNPs.

Targeting and detecting cancer cells using spontaneously formed multifunctional dendrimer-stabilized gold nanoparticles.

We develop a facile approach to fabricating multifunctional dendrimer-stabilized gold nanoparticles (Au DSNPs) for cancer cell targeting and imaging. In this work, amine-terminated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers pre-functionalized with folic acid (FA) and fluorescein isothiocyanate (FI) are complexed with Au(III) ions, followed by acetylation of the amine groups on the dendrimer surfaces. This one-step process leads to the spontaneous formation of 6 nm-sized Au nanoparticles stabilized by multifunctional dendrimers bearing both targeting and imaging functionalities. The multifunctional Au DSNPs are characterized by UV-Vis spectrometry, 1H NMR, and transmission electron microscopy (TEM). The formed Au DSNPs are water-soluble, stable, and biocompatible. Combined flow cytometry, confocal microscopy, silver staining, and inductively coupled plasma-mass spectrometry (ICP-MS) analyses show that the FA- and FI-functionalized Au DSNPs can specifically target to cancer cells expressing high-affinity FA receptors in vitro. This approach to functionalizing Au DSNPs may be extended to other targeting molecules, providing a unique nanoplatform for targeting and imaging of a variety of biological systems.

Spontaneous Formation of Functionalized Dendrimer-Stabilized Gold Nanoparticles.

Functionalized, dendrimer-stabilized gold nanoparticles (Au DSNPs) are of scientific and technological interest for biological applications. In this work, we show that acetamide-functionalized Au DSNPs can be formed by acetylation of amine-terminated poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH(2)) complexed with Au(III) ions (AuCl(4) (-)). In addition, hydroxyl-functionalized Au DSNPs can be formed by simply mixing the glycidol hydroxyl-terminated G5 dendrimers (G5.NGlyOH) with HAuCl(4). In both cases, no additional reducing agents were needed and the reactions were completed at room temperature. We also show that Alexa Fluor 594 dye-functionalized Au DSNPs can be formed by acetylation of Alexa Fluor 594-conjugated, amine-terminated G5 dendrimers complexed with HAuCl(4). All of these functionalized Au DSNPs are water-soluble and stable. Fluorescence spectroscopy studies reveal that the Alexa Fluor 594-functionalized Au DSNPs retain similar fluorescence intensity to the Alexa Fluor 594-functionalized dendrimers that lack Au nanoparticles. These preparations of Au DSNPs provide a straightforward approach to synthesizing functionalized metal nanoparticles for biomedical applications.

Assembly of myoglobin layer-by-layer films with poly(propyleneimine) dendrimer-stabilized gold nanoparticles and its application in electrochemical biosensing

The small-sized Au nanoparticles (3nm) were prepared by reduction of HAuCl4 in the presence of poly(propyleneimine) (PPI) dendrimers, forming the stable PPI–Au nanoclusters in aqueous medium. The PPI–Au nanoclusters might take a kind of “core–shell” structure, in which several PPI molecules were attached on the surface of one gold nanoparticle. The PPI–Au nanoclusters in aqueous dispersions and myoglobin (Mb) in its buffers at pH 5.0 were then alternately adsorbed on the surface of pyrolytic graphite (PG) electrodes and other solid substrates, forming {PPI–Au/Mb}n layer-by-layer films, which was confirmed by cyclic voltammetry (CV) and quartz crystal microbalance (QCM). {PPI–Au/Mb}n films on PG electrodes demonstrated a pair of well-defined and quasi-reversible CV reduction-oxidation peaks for Mb heme FeIII/FeII couple and good electrocatalytic properties toward reduction of oxygen and hydrogen peroxide. Compared with {Au/Mb}n multilayer films containing no dendrimers and {PAMAM/Mb}n films assembled by polyamidoamine (PAMAM) dendrimers and Mb but in the absence of Au nanoparticles, {PPI–Au/Mb}n films showed better electrochemical behaviors and catalytic performances, which may be attributed to the unique structure of PPI–Au nanoclusters and good conductivity of gold nanoparticles. This novel kind of protein multilayer films assembled with dendrimer-stabilized gold nanoparticles may provide a new and general approach to fabricate the biosensors and bioreactors based on the direct electrochemistry of proteins or enzymes.

Characterization of crystalline dendrimer-stabilized gold nanoparticles

Monodispersed, highly crystalline dendrimer-stabilized gold nanoparticles (Au DSNPs)were synthesized via hydrazine reduction chemistry and stabilized using primaryamine-terminated poly(amidoamine) (PAMAM) dendrimers of different generations(generations 2–6) with the same molar ratios of dendrimer terminal nitrogen ligands/goldatoms. The sizes of the synthesized Au DSNPs decrease with the increase of the number ofdendrimer generations. These Au DSNPs are fluorescent and display strong blue emissionintensity at 458 nm. Polyacrylamide gel electrophoresis (PAGE) analysis indicates that allAu DSNPs are stable and both metal NPs and dendrimer stabilizers do not separate fromeach other during the electrophoresis process. The synthesized inorganic/organic hybrid AuDSNPs provide new nanoplatforms that will be further modified with variousbiological ligands for the application of biosensing and targeted cancer therapeutics.

Supramolecular Microcontact Printing and Dip‐Pen Nanolithography on Molecular Printboards

The transfer of functional molecules onto self-assembled monolayers (SAMs) by means of soft and scanning-probe lithographic techniques-microcontact printing (muCP) and dip-pen nanolithography (DPN), respectively-and the stability of the molecular patterns during competitive rinsing conditions were examined. A series of guests with different valencies were transferred onto beta-cyclodextrin- (beta-CD-) terminated SAMs and onto reference hydroxy-terminated SAMs. Although physical contact was sufficient to generate patterns on both types of SAMs, only molecular patterns of multivalent guests transferred onto the beta-CD SAMs were stable under the rinsing conditions that caused the removal of the same guests from the reference SAMs. The formation of kinetically stable molecular patterns by supramolecular DPN with a lateral resolution of 60 nm exemplifies the use of beta-CD-terminated SAMs as molecular printboards for the selective immobilization of printboard-compatible guests on the nanometer scale through the use of specific, multivalent supramolecular interactions. Electroless deposition of copper on the printboard was shown to occur selectively on the areas patterned with dendrimer-stabilized gold nanoparticles.

Voltammetric study of sodium hypochlorite using dendrimer-stabilized gold nanoparticles

Electrochemical activity of dendrimer-stabilized gold nanoparticles on a glassy carbon electrode (GCE) was studied by means of cyclic voltammetry of sodium hypochlorite. Dendrimer-stabilized gold nanoparticles were deposited onto a glassy carbon surface by electrophoresis and the deposition was observed by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Both anodic and cathodic peak currents were found to increase after the deposition of dendrimer-stabilized gold nanoparticles. In the case of dendrimers deposited onto the GCE surface, the magnitude of the current was smaller than for dendrimer-stabilized-gold-nanoparticle-modified GCE. This indicates the enhancement in the rate of electrolysis due to gold nanoparticles.