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In this study, amine-terminated generation 5 poly(amidoamine) dendrimers were used as templates or stabilizers to synthesize dendrimer-entrapped or dendrimer-stabilized Au-Ag alloy nanoparticles (NPs) with different gold atom/silver atom/dendrimer molar ratios with the assistance of sodium borohydride reduction chemistry. Following a one-step acetylation reaction to transform the dendrimer terminal amines to acetyl groups, a series of dendrimer-entrapped or dendrimer-stabilized Au-Ag alloy NPs with terminal acetyl groups were formed. The formed Au-Ag alloy NPs before and after acetylation reaction were characterized using different techniques. We showed that the optical property and the size of the bimetallic NPs were greatly affected by the metal composition. At the constant total metal atom/dendrimer molar ratio, the size of the alloy NPs decreased with the gold content. The formed Au-Ag alloy NPs were stable at different pH (pH 5-8) and temperature (4-50°C) conditions. X-ray absorption coefficient measurements showed that the attenuation of the binary NPs was dependent on both the gold content and the surface modification. With the increase of gold content in the binary NPs, their X-ray attenuation intensity was significantly enhanced. At a given metal composition, the X-ray attenuation intensity of the binary NPs was enhanced after acetylation. Cytotoxicity assays showed that after acetylation, the cytocompatibility of Au-Ag alloy NPs was significantly improved. With the controllable particle size and optical property, metal composition-dependent X-ray attenuation characteristics, and improved cytocompatibility after acetylation, these dendrimer-entrapped or dendrimer-stabilized Au-Ag alloy NPs should have a promising potential for CT imaging and other biomedical applications.

One major method used to evaluate the biocompatibility of porous tissue engineering scaffolding materials is MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The MTT cell viability assay is based on the absorbance of the dissolved MTT formazan crystals formed in living cells, which is proportional to the number of viable cells. Due to the strong dye sorption capability of porous scaffolding materials, we propose that the cell viability determined from the MTT assay is likely to give a false negative result. In this study, we aim to explore the effect of the adsorption of MTT formazan on the accuracy of the viability assay of cells cultured onto porous electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, HNTs (halloysite nanotubes)/PLGA, and CNTs (multiwalled carbon nanotubes)/PLGA composite nanofibrous mats. The morphology of electrospun nanofibers and L929 mouse fibroblasts cultured onto the nanofibrous scaffolds were observed using scanning electron microscopy. The viability of cells proliferated for 3 days was evaluated through the MTT assay. In the meantime, the adsorption of MTT formazan onto the same electrospun nanofibers was evaluated and the standard concentration–absorbance curve was obtained in order to quantify the contribution of the adsorbed MTT formazan during the MTT cell viability assay. We show that the PLGA, and the HNTs- or CNTs-doped PLGA nanofibers display appreciable MTT formazan dye sorption, corresponding to 35.6–50.2% deviation from the real cell viability assay data. The better dye sorption capability of the nanofibers leads to further deviation from the real cell viability. Our study gives a general insight into accurate MTT cytotoxicity assessment of various porous tissue engineering scaffolding materials, and may be applicable to other colorimetric assays for analyzing the biological properties of porous scaffolding materials.

Fe/Pd bimetallic nanoparticles (NPs) have held great promise for treating trichloroethylene (TCE)-contaminated groundwater, without the accumulation of chlorinated intermediates. However, the conventionally used colloidal Fe/Pd NPs usually aggregate rapidly, resulting in a reduced reactivity. To reduce the particle aggregation, we employed electrospun polyacrylic acid (PAA)/polyvinyl alcohol (PVA) polymer nanofibers as a nanoreactor to immobilize Fe/Pd bimetallic NPs. In the study, the water-stable PAA/PVA nanofibrous mats were complexed with Fe (III) ions via the binding with the free carboxyl groups of PAA for subsequent formation and immobilization of zero-valent iron (ZVI) NPs. Fe/Pd bimetallic NPs were then formed by the partial reduction of Pd(II) ions with ZVI NPs. The formed electrospun nanofibrous mats containing Fe/Pd bimetallic NPs with a diameter of 2.8 nm were characterized by scanning electron microscopy, energy-dispersive spectroscopy, transmission electron microscopy, thermogravimetric analysis, and inductively coupled plasma-atomic emission spectroscopy. The Fe/Pd NP-containing electrospun PAA/PVA nanofibrous mats exhibited higher reactivity than that of the ZVI NP-containing mats or colloidal Fe/Pd NPs in the dechlorination of trichloroethylene (TCE), which was used as a model contaminant. With the high surface area to volume ratio, high porosity, and great reusability of the fibrous mats immobilized with the bimetallic NPs, the composite nanofibrous mats should be amenable for applications in remediation of various environmental contaminants.

In molecular biology, polymerase chain reaction (PCR) has played an important role but suffers a general problem with low efficiency and specificity. Development of suitable additives to improve the PCR specificity and efficiency and the understanding of the PCR enhancing mechanism still remain a great challenge. Here we report the use of polyethyleneimine (PEI)-modified multiwalled carbon nanotubes (MWCNTs) with different surface charge polarities as a novel class of enhancers to improve the specificity and efficiency of PCR. The materials used included the positively charged PEI-modified MWCNTs (CNT/PEI), the neutral CNT/PEI modified with acetic anhydride (CNT/PEI.Ac), and the negatively charged CNT/PEI modified with succinic anhydride (CNT/PEI.SAH). We show that the specificity and efficiency of an error-prone two-round PCR are greatly impacted by the surface charge polarity of the PEI-modified MWCNTs. Positively charged CNT/PEI could significantly enhance the specificity and efficiency of PCR with an optimum concentration as low as 0.39 mg L(-1), whereas neutral CNT/PEI.Ac had no such effect. Although negatively charged CNT/PEI.SAH could enhance the PCR, the optimum concentration required (630 mg L(-1)) was more than 3 orders of magnitude higher than that of positively charged CNT/PEI. The present study suggests that the PCR enhancing effect may be primarily based on the electrostatic interaction between the positively charged CNT/PEI and the negatively charged PCR components, rather than only on the thermal conductivity of MWCNTs.

Organic/inorganic hybrid nanofiber systems have generated great interest in the area of tissue engineering and drug delivery. In this study, halloysite nanotube (HNT)-doped poly(lactic-co-glycolic acid) (PLGA) composite nanofibers were fabricated via electrospinning and the influence of the incorporation of HNTs within PLGA nanofibers on their in vitro biocompatibility was investigated. The morphology, mechanical and thermal properties of the composite nanofibers were characterized by scanning electron microscopy (SEM), tensile test, differential scanning calorimetry and thermogravimetric analysis. The adhesion and proliferation of mouse fibroblast cells cultured on both PLGA and HNT-doped PLGA fibrous scaffolds were compared through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay of cell viability and SEM observation of cell morphology. We show that the morphology of the PLGA nanofibers does not appreciably change with the incorporation of HNTs, except that the mean diameter of the fibers increased with the increase of HNT incorporation in the composite. More importantly, the mechanical properties of the nanofibers were greatly improved. Similar to electrospun PLGA nanofibers, HNT-doped PLGA nanofibers were able to promote cell attachment and proliferation, suggesting that the incorporation of HNTs within PLGA nanofibers does not compromise the biocompatibility of the PLGA nanofibers. In addition, we show that HNT-doped PLGA scaffolds allow more protein adsorption than those without HNTs, which may provide sufficient nutrition for cell growth and proliferation. The developed electrospun HNT-doped composite fibrous scaffold may find applications in tissue engineering and pharmaceutical sciences.

Effects of different coatings on the tribological properties of very thin oil films in the nanoscale were investigated. The film thickness and friction force were measured by the technique of relative optical interference intensity (ROII) and a stress–strain force measuring system with high precision. The results indicate that the film thickness complies with the elastohydrodynamic theory in the high-speed region but it differs from the theory in the low-speed region. The physicochemical properties of coating surfaces have a great effect on the tribological properties of the oil film in the nanoscale. The coating with higher surface energy gives rise to a thicker film and a higher friction coefficient. The reasons for enhancement in the friction coefficient of the oil film in the nanoscale are discussed. Copyright © 2001 John Wiley & Sons, Ltd.

We report a new use of acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for in vitro and in vivo computed tomography (CT) imaging of cancer cells. In this study, Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers were subjected to an acetylation reaction to neutralize the positive surface potential. The acetylated Au DENPs were used for both in vitro and in vivo CT imaging of a human lung adencarcinoma cell line (SPC-A1 cells). Micro-CT images show that SPC-A1 cells can be detected under X-ray after incubation with the acetylated Au DENPs in vitro and the xenograft tumor model can be imaged after both intratumoral and intraperitoneal administration of the particles. Transmission electron microscopy data further confirm that the acetylated Au DENPs are able to be uptaken dominantly in the lysosomes of the cells. Combined morphological observation of cells after hematoxylin and eosin staining, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay of cell viability, and flow cytometric analysis of cell cycle show that the acetylated Au DENPs do not appreciably affect the cell morphology, viability, and cell cycle, indicating their good biocompatibility at the given concentration range. Findings from this study suggest that the developed acetylated Au DENPs have a great potential to be used for CT imaging of cancer cells.

We report the fabrication of multiwalled carbon nanotube (MWCNT)-incorporated electrospun polyvinyl alcohol (PVA)/chitosan (CS) nanofibers with improved cellular response for potential tissue engineering applications. In this study, smooth and uniform PVA/CS and PVA/CS/MWCNTs nanofibers with water stability were formed by electrospinning, followed by crosslinking with glutaraldehyde vapor. The morphology, structure, and mechanical properties of the formed electrospun fibrous mats were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing, respectively. We showed that the incorporation of MWCNTs did not appreciably affect the morphology of the PVA/CS nanofibers; importantly the protein adsorption ability of the nanofibers was significantly improved. In vitro cell culture of mouse fibroblasts (L929) seeded onto the electrospun scaffolds showed that the incorporation of MWCNTs into the PVA/CS nanofibers significantly promoted cell proliferation. Results from this study hence suggest that MWCNT-incorporated PVA/CS nanofibrous scaffolds with small diameters (around 160 nm) and high porosity can mimic the natural extracellular matrix well, and potentially provide many possibilities for applications in the fields of tissue engineering and regenerative medicine.

Recent advances in dendrimer-based nanomedicine show that dendrimers have been used in many different ways in medical applications. Dendrimer can be used as a platform to covalently conjugate targeting moieties and to physically encapsulate drug molecules inside their interior to improve the water solubility and bioavailability of the drugs. Various types of analytical techniques have been used to characterize dendrimeric nanoparticles, including capillary electrophoresis (CE). This article gives an overview of the recent advances of CE analysis and characterization of various dendrimer nanomaterials from simple dendrimer derivatives to complex multifunctional dendrimeric medical nanodevices. Keywords: capillary electrophoresis (CE); dendrimers; nanoparticles; nanodevices

Polyacrylic acid (PAA) is an important polymer material for metal ion complexation and for nanocomposite materials syntheses. Generating ultrafine, uniform, and stable PAA nanofibers is of great scientific and technological interest for various applications. In this study, we systematically investigated the influence of processing parameters on the morphology and stability of the electrospun ultrafine PAA nanofibers. We show that a higher concentration (up to 25 wt %) favored the formation of uniform PAA nanofibers, whereas at the concentration of 10 wt %, only bead structures were produced. Increasing the applied voltage (up to 22.5 kV) resulted in more uniform PAA nanofibers. In addition, longer collection distance (20 cm) was beneficial for the evaporation of solvent and for decreasing the adhesion between nanofibers, thus leading to the nanofibrous mats with high porosity. Finally, the PAA nanofibers could be rendered water insoluble by heating the electrospun composite PAA/polyvinyl alcohol (PVA) nanofibers at 145°C for 30 min. The resulting nanofibrous mats exhibited excellent performance to remove Cu(II) ions in aqueous solution. The formed nanofibers may find various applications in ultrafiltration, separation, and environmental sciences. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Background Increased arterial stiffness could represent an intermediate subclinical outcome in the mechanistic pathway underlying associations between average long-term pollution exposure and cardiovascular events. Objective We hypothesized that 20 years of exposure to particulate matter (PM) ≤ 2.5 and 10 μm in aerodynamic diameter (PM2.5 and PM10, respectively) would be positively associated with arterial stiffness in 3,996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were seen at six U.S. study sites. Methods We assigned pollution exposure during two decades preceding a clinical exam (2000–2002) using observed PM10 from monitors nearest participants’ residences and PM10 and PM2.5 imputed from a space-time model. We examined three log-transformed arterial stiffness outcome measures: Young’s modulus (YM) from carotid artery ultrasound and large (C1) and small (C2) artery vessel compliance from the radial artery pulse wave. All associations are expressed per 10 μg/m3 increment in PM and were adjusted for weather, age, sex, race, glucose, triglycerides, diabetes, waist:hip ratio, seated mean arterial pressure, smoking status, pack-years, cigarettes per day, environmental tobacco smoke, and physical activity. C1 and C2 models were further adjusted for heart rate, weight, and height. Results Long-term average particle exposure was not associated with greater arterial stiffness measured by YM, C1, or C2, and the few associations observed were not robust across metrics and adjustment schemes. Conclusions Long-term particle mass exposure did not appear to be associated with greater arterial stiffness in this study sample.

Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au0)51.2-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au0)51.2-G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 936–942, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

PURPOSE: This study examined associations of neighborhood social cohesion, violence, and aesthetic quality with depressive symptoms among 2,619 healthy adults aged 45-84 years enrolled in the Multiethnic Study of Atherosclerosis. METHODS: Neighborhood characteristics were estimated by surveying a separate sample of area residents. Measures of aesthetic environment, social cohesion, and violence were combined into a summary score with increasing scores indicating more favorable environments. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale. Marginal maximum likelihood estimation was used to assess associations of neighborhood characteristics with CES-D score at baseline and with the odds of developing incident depression (CES-D score >/=16 or use of antidepressants) over a 4-5 year follow-up among persons with CES-D less than 16 at baseline. Models were adjusted for age, income, education, and race/ethnicity. RESULTS: Lower levels of social cohesion and aesthetic quality and higher levels of violence were associated with higher mean CES-D scores in men and women (P for trend

Capturing circulating tumor cells (CTCs) with sufficient sensitivity and specificity in vitro is of paramount importance for early cancer diagnosis. Here a facile approach to immobilizing hyaluronic acid (HA) onto electrospun polyvinyl alcohol/polyethyleneimine (PVA/PEI) nanofibers for capturing cancer cells overexpressing CD44 receptors is reported. In this study, electrospun PVA/PEI nanofibers were crosslinked using glutaraldehyde vapor, covalently conjugated with HA via N-(3-dimethy-laminopropyl)-N′-ethylcarbodiimide/N-hydroxysuccinimide coupling reaction, followed by neutralization of the remaining fiber surface PEI amines via acetylation. The formed nanofibers were characterized using different techniques. It is shown that the HA-modified PVA/PEI nanofibers with a mean diameter of 459.7 nm possess a smooth and uniform fibrous morphology, similar to the PVA/PEI nanofibers without HA modification. The HA-modified PVA/PEI nanofibers display good cytocompatibility and hemocompatibility as confirmed by cell viability, hemolysis, and anticoagulant assays. Importantly, with the modified HA, the nanofibers exhibit superior capability to capture CD44 receptor-overexpressing cancer cells. The developed HA-modified PVA/PEI nanofibers may hold a great promise to be applied for capturing CTCs for cancer diagnosis applications.

This paper describes the use of arrays of horizontally-oriented reservoirs to deliver liquids through microchannels at a constant flow rate over extended periods of time (hours to days). The horizontal orientation maintains a constant hydraulic pressure drop across microfluidic channels even as the volumes of liquids within the reservoirs change over time. For a given channel–reservoir system, the magnitude of the flow velocity depends linearly on the height difference between reservoirs. The simple structure and operation mechanism make this pumping system versatile. A one-inlet–one-outlet system was used to continuously deliver media for perfusion cell culture, and an array of inlet reservoirs coupled to an outlet reservoir via microchannels was used to drive flows of multiple laminar streams. The parallel pumping scheme conveniently generated various smooth and step concentration gradients, and allowed evaluation of the effect of colchicine on myoblasts. Since the reservoir arrays are configured to be compatible with commercialized multichannel pipettors designed for 96 well plate handling, this simple pumping scheme is envisioned to be broadly useful for medium to high throughput microfluidic perfusion cell culture assays, cell migration assays, multiple laminar flow drug tests, and any other applications needing multiple microfluidic streams.

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.

We report here the use of dendrimer-stabilized silver nanoparticles (Ag DSNPs) for the highly sensitive and selective colorimetric detection of mercury ions (Hg2+) in aqueous solution. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers were employed as stabilizers to complex Ag+ ions for the subsequent reductive formation of colloidally stable Ag DSNPs with a mean size of 12.1 nm. The redox reaction between Ag DSNPs and Hg2+ was confirmed by UV-Vis spectroscopy, transmission electron microscopy, and dynamic light scattering. We show that the size of the Ag DSNPs is decreased after interaction with Hg2+ and the yellow color of the Ag DSNP solution is gradually decolorized as a function of the concentration of Hg2+. The Hg2+ concentration-dependent changes in the intensity and the shift of the surface plasmon resonance peak of the Ag DSNPs at 398 nm were used to detect Hg2+ via two different correlations. In both correlations, Hg2+ was able to be detected in aqueous solution in a concentration range of 10 ppb to 10 ppm. Finally, the use of Ag DSNPs for Hg2+ detection was found to be specific to Hg2+. Our results clearly indicate that Ag DSNPs could be used as an efficient probe for the colorimetric sensing of Hg2+ in environmental water samples.

Generation 5-poly(amidoamine) dendrimers pre-modified with folic acid and methotrexate (G5-FA-MTX) were used as templates for the synthesis of dendrimer-entrapped gold nanoparticles (Au DENPs). The synthesized [(Au0)50-G5-FA-MTX] DENPs were able to target and specifically inhibit the growth of cancer cells overexpressing high affinity folic acid receptors.

We describe a facile approach to synthesizing acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) with enhanced Au loading in the dendrimer interior. In this study, amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH2) were used as templates to form Au DENPs via a stepwise Au salt complexation/reduction approach, followed by acetylation of the dendrimer terminal amines. The formed Au DENPs before and after acetylation were characterized with different techniques. We show that the stepwise complexation/reduction of HAuCl4 is able to significantly improve the loading amount of Au within the dendrimer interior. UV-Vis spectroscopy reveals that the intensity of the surface plasmon resonance (SPR) band increases with the Au loading, confirming the stepwise loading synthesis of Au DENPs. TEM images show that the synthesized Au DENPs have a quite uniform size distribution with sizes tunable in the range of 2–4 nm depending on the Au loading. The formed acetylated Au DENPs with enhanced Au loading are very stable under different pH and temperature conditions. Importantly, computed tomography (CT) imaging experiments reveal that the formed acetylated Au DENPs have higher attenuation intensity than a clinically used iodinated contrast agent, Omnipaque, at the same molar concentration of active elements (Au or iodine), and enable significantly enhanced CT imaging of rat heart in vivo. The acetylated Au DENPs with enhanced Au loading formed via the facile stepwise approach may be used as contrast agents for highly sensitive CT imaging applications.

Colloidal Fe/Ni bimetallic nanoparticles (NPs) have been applied as important materials for environmental remediation applications; however, the reusability of the colloidal Fe/Ni NPs still remains a great issue that limits their environmental applications. In this paper, we developed two different routes to synthesize and immobilize Fe/Ni bimetallic NPs using electrospun polyacrylic acid/polyvinyl alcohol nanofibers as nanoreactors: (1) synthesis of Fe NPs followed by post-coating Ni on Fe NPs (referred to post-coated Fe/Ni NPs) and (2) co-reduction of nickel and iron precursors within the nanofibers (referred to co-reduced Ni/Fe NPs). The formed electrospun nanofibrous mats containing Fe/Ni bimetallic NPs were characterized via different techniques. The decoloration efficiency of the two kinds of Fe/Ni NP-containing nanofibrous mats was compared with that of single metal zero-valent iron NP-containing nanofibrous mats. We show that the co-reduced Fe/Ni NP-containing nanofibrous mats have much higher decoloration efficiency than the single iron NP-immobilized polymer mats; whereas the mats containing post-coated Fe/Ni NPs have lower decoloration efficiency than the single iron NP-containing mats. The formed co-reduced Fe/Ni NP-containing polymer nanofibers can be reused for at least 4 times with high decoloration efficiency. With the easiness of formation and convenient reusability and recyclability, the bimetallic NP-containing polymer nanofibers could be applied in different potential applications including environmental remediation, fuel cells, and electrochemical sensors.

The development of multifunctional nanoprobes with a targeting capability for efficient molecular imaging of tumors still remains a great challenge. Herein, we report the synthesis and characterization of folic acid (FA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) via a facile polyethylene glycol (PEG) linking strategy for in vivo targeted tumor computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) sequentially modified by two types of PEG moieties (PEG monomethyl ether with one end of carboxyl group (mPEG-COOH), and FA-modified PEG with one end of carboxyl group (FA-PEG-COOH)) were used as templates to synthesize AuNPs within the dendrimer interiors, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. Cell viability assay, flow cytometric analysis of the cell cycles, and hemolysis assay were used to assess the cytotoxicity and hemocompatibility of the particles. We show that the formed multifunctional Au DENPs are stable at different pH and temperature conditions and in different aqueous media, cytocompatible and hemocompatible in the given Au concentration range, and display much higher X-ray attenuation intensity than Omnipaque (an iodine-based CT contrast agent) under similar concentrations of the active element (Au or iodine). Moreover, the developed Au DENPs enable targeted CT imaging of the model cancer cells with high FA receptor expression in vitro and the corresponding xenografted tumor model in vivo. These findings suggest that the designed Au DENPs may be used as promising contrast agents for targeted CT imaging of tumors.

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.

The purpose of this study was to evaluate dendrimer-entrapped gold nanoparticles [Au DENPs] as a molecular imaging [MI] probe for computed tomography [CT]. Au DENPs were prepared by complexing AuCl4 - ions with amine-terminated generation 5 poly(amidoamine) [G5.NH2] dendrimers. Resulting particles were sized using transmission electron microscopy. Serial dilutions (0.001 to 0.1 M) of either Au DENPs or iohexol were scanned by CT in vitro. Based on these results, Au DENPs were injected into mice, either subcutaneously (10 μL, 0.007 to 0.02 M) or intravenously (300 μL, 0.2 M), after which the mice were imaged by micro-CT or a standard mammography unit. Au DENPs prepared using G5.NH2 dendrimers as templates are quite uniform and have a size range of 2 to 4 nm. At Au concentrations above 0.01 M, the CT value of Au DENPs was higher than that of iohexol. A 10-μL subcutaneous dose of Au DENPs with [Au] ≥ 0.009 M could be detected by micro-CT. The vascular system could be imaged 5 and 20 min after injection of Au DENPs into the tail vein, and the urinary system could be imaged after 60 min. At comparable time points, the vascular system could not be imaged using iohexol, and the urinary system was imaged only indistinctly. Findings from this study suggested that Au DENPs prepared using G5.NH2 dendrimers as templates have good X-ray attenuation and a substantial circulation time. As their abundant surface amine groups have the ability to bind to a range of biological molecules, Au DENPs have the potential to be a useful MI probe for CT.

We report a facile approach for fabrication of Fe3O4@Au nanocomposite particles (NCPs) as a dual mode contrast agent for both magnetic resonance (MR) and computed tomography (CT) imaging applications. In this study, Fe3O4 nanoparticles (NPs) prepared by a controlled coprecipitation approach were used as core particles for subsequent electrostatic layer-by-layer (LbL) assembly of poly(γ-glutamic acid) (PGA) and poly(L-lysine) (PLL) to form PGA/PLL/PGA multilayers, followed by assembly with dendrimer-entrapped gold NPs (Au DENPs) formed using amine-terminated generation 5 poly(amidoamine) dendrimers as templates. After crosslinking the multilayered shell of PGA/PLL/PGA/Au DENPs via EDC chemistry, the remaining amine groups of the outermost layer of Au DENPs were acetylated to neutralize the surface charge of the particles. The formed Fe3O4@Au NCPs were well characterized via different techniques. We show that the formed Fe3O4@Au NCPs are colloidally stable, hemocompatible, and biocompatible in the given concentration range (0–100 μg mL−1). The relatively high r2 relaxivity (71.55 mM−1 s−1) and enhanced X-ray attenuation property when compared with either the uncoated Fe3O4 NPs or the Au DENPs afford the developed Fe3O4@Au NCPs with a capacity not only for dual mode CT and MR imaging of cells in vitro, but also for MR imaging of liver and CT imaging of subcutaneous tissue in vivo. With the facile integration of both Fe3O4 NPs and Au DENPs within one particle system via the LbL assembly technique and dendrimer chemistry, it is expected that the fabricated Fe3O4@Au NCPs may be further modified with multifunctionalities for multi-mode imaging of various biological systems.

We report the fabrication of uniform electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporated with laponite (LAP) nanodisks, a synthetic clay material for osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, a solution mixture of LAP suspension and PLGA was electrospun to form composite PLGA–LAP nanofibers with different LAP doping levels. The PLGA–LAP composite nanofibers formed were systematically characterized via different techniques. We show that the incorporation of LAP nanodisks does not significantly change the uniform PLGA fiber morphology, instead significantly improves the mechanical durability of the nanofibers. Compared to LAP-free PLGA nanofibers, the surface hydrophilicity and protein adsorption capacity of the composite nanofibers slightly increase after doping with LAP, while the hemocompatibility of the fibers does not appreciably change. The cytocompatibility of the PLGA–LAP composite nanofibers was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of L929 mouse fibroblasts and porcine iliac artery endothelial cells cultured onto the surface of the nanofibers. The results reveal that the incorporated LAP is beneficial to promote the cell adhesion and proliferation to some extent likely due to the improved surface hydrophilicity and protein adsorption capability of the fibers. Finally, the PLGA–LAP composite nanofibers were used as scaffolds for osteogenic differentiation of hMSCs. We show that both PLGA and PLGA–LAP composite nanofibers are able to support the osteoblast differentiation of hMSCs in osteogenic medium. Most strikingly, the doped LAP within the PLGA nanofibers is able to induce the osteoblast differentiation of hMSCs in growth medium without any inducing factors. The fabricated smooth and uniform organic–inorganic hybrid LAP-doped PLGA nanofibers may find many applications in the field of tissue engineering.

We report here a general approach to using multifunctional poly(amidoamine) (PAMAM) dendrimer-based platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, generation 5 (G5) PAMAM dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) via covalent conjugation, and with remaining terminal amines being acetylated (G5.NHAc-FI-FA) were used to complex DOX for targeted delivery of the drug to cancer cells overexpressing high-affinity folic acid receptors (FAR). We show that the formed G5.NHAc-FI-FA/DOX complexes with each dendrimer encapsulating approximately one DOX molecule are water soluble and stable. In vitro release studies show that DOX complexed with the multifunctional dendrimers can be released in a sustained manner. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc-FI-FA/DOX complexes can specifically target and display specific therapeutic efficacy to cancer cells overexpressing high-affinity FAR. Findings from this study suggest that multifunctional dendrimers may be used as a general drug carrier to encapsulate various cancer drugs for targeting therapy of different types of cancer.

We report a facile approach to immobilizing gold nanoparticles (AuNPs) into electrospun polyethyleneimine (PEI)/polyvinyl alcohol (PVA) nanofibers for catalytic applications. In this study, electrospun PEI/PVA nanofibers with a mean diameter of 490 nm were first crosslinked with glutaraldehyde vapor to render them water stable. Then, the water-insoluble nanofibrous mats were used as nanoreactors to complex AuCl4− anions via binding with the free amine groups of PEI for subsequent formation and immobilization of AuNPs. The formed AuNPs with a diameter of 11.8 nm within the nanofibers do not significantly change the morphology of the nanofibers; while importantly the mechanical property of the fibers was greatly improved compared to the crosslinked fibers without AuNPs. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, energy dispersive spectroscopy, and thermogravimetric analysis were used to characterize these hybrid nanofibers. Furthermore, we show that the AuNP-containing nanofibers display an excellent catalytic activity and reusability for the transformation of 4-nitrophenol to 4-aminophenol. The present approach to fabricating AuNP-containing nanofibers may be extended for producing other nanoparticle-containing composite nanofibrous materials for various applications in catalysis, sensing, and biomedical sciences.

We describe a unique approach to combining two kinds of radiodense elements, gold and iodine, within one single dendrimer-based nanodevice with an enhanced X-ray attenuation property for potential computed tomography (CT) imaging applications. In this approach, amine-terminated generation 5 poly(amidoamine) dendrimers were used as templates for the entrapped synthesis of gold nanoparticles (AuNPs). The dendrimer-entrapped AuNPs (Au DENPs) were then conjugated with diatrizoic acid (DTA) via an EDC coupling reaction, resulting in the loading of 59 DTA molecules on average within each Au DENP nanodevice, where only 13 DTA molecules were covalently attached onto the surface of each dendrimer. The formed Au DENP–DTA nanocomplexes possessed a good stability in aqueous solution. X-ray absorption coefficient measurements reveal that the attenuation effect of Au DENP–DTA is much higher than that of both the commercial iodine-based contrast agent at the same iodine concentration and pure Au DENPs at the same gold concentration. With the prolonged circulation time of NPs, the Au DENP–DTA nanocomplex is expected to have a high efficacy as a contrast agent in dynamic CT imaging and angiography. This work demonstrates for the first time the enhancing effect of two different radiodense elements within the architecture of one contrast agent, presenting a novel concept for designing high-performance contrast agents for biomedical CT imaging applications.

We report the complexation of a potential anticancer agent 2-methoxyestradiol (2-ME) with generation 5 (G5) poly(amidoamine) dendrimers having different surface functional groups for therapeutic applications. The complexation experiment shows that approximately 6-8 drug molecules can be complexed with one dendrimer molecule regardless the type of the dendrimer terminal groups. The bioactivity of 2-ME complexed with dendrimers was found to be significantly dependent on the surface charge of G5 dendrimers. In vitro cell biological assays show that amine, hydroxyl, and acetamide-terminated G5 dendrimers with positive, slightly positive, and close to neutral surface charges, respectively are able to deliver 2-ME to inhibit cancer cell growth. In contrast, 2-ME complexed with carboxyl-terminated G5 dendrimers with negative surface charges does not show its inherent bioactivity. Further molecular dynamics simulation studies show that the compact structure of carboxylated G5 dendrimers complexed with 2-ME does not allow the release of the drug molecules even at a pH of 5.0, which is the typical pH value in lysosome. Our findings indicate that the surface modification of dendrimers with different charges is crucial for the development of formulations of various anticancer drugs for therapeutic applications.

We report a facile size-controlled synthesis of dendrimer-stabilized silver nanoparticles (Ag DSNPs) for X-ray computed tomography (CT) imaging applications. Amine-terminated generation 5 poly(amidoamine) dendrimers were used as templates to complex Ag(I) ions for subsequent reductive formation of dendrimer-entrapped Ag nanoparticles. Following a one-step acetylation reaction to transform dendrimer terminal amine to acetyl groups, Ag DSNPs can be formed. The formed Ag DSNPs were characterized using 1H NMR, UV-Vis spectrometry, transmission electron microscopy, and ζ-potential measurements. We show that through the variation of the dendrimer/Ag salt molar ratio, the size of Ag DSNPs can be controlled at the range of 8.8–23.2 nm. The formed Ag DSNPs are stable not only in water, PBS buffer, and fetal bovine serum, but also at different pH conditions (pH 5–8) and temperatures (20–50 °C). X-Ray absorption coefficient measurements show that the attenuation of Ag DSNPs is size-dependent, and the Ag DSNPs with a diameter of 16.1 nm display an X-ray attenuation intensity close to that of a clinically used iodine-based contrast agent (Omnipaque) at the same molar concentration of the active element (Ag versus iodine). This suggests that Ag DSNPs with an appropriate size have a great potential to be used as a CT imaging contrast agent, although the atomic number of Ag is lower than that of iodine. Furthermore, CT scanning showed prolonged enhancement at the point of mice injected subcutaneously with Ag DSNPs, rendering them as a promising contrast agent in CT imaging applications.

A new approach to immobilizing zero-valent iron nanoparticles (ZVI NPs) into electrospun polymer nanofibers with enhanced mechanical properties for environmental applications is presented. In this approach, multiwalled carbon nanotubes (MWCNTs) are mixed with polyacrylic acid (PAA)/polyvinyl alcohol (PVA) mixture polymer solution for subsequent electrospinning to form uniform nanofibers. The MWCNT-incorporated PAA/PVA nanofibers are crosslinked and then used as a nanoreactor to complex Fe(III) ions through binding with the PAA carboxyl groups for the reductive formation of ZVI NPs. The MWCNT-incorporated PAA/PVA nanofibers before and after immobilization with ZVI NPs are characterized using scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and mechanical property measurements. We show that the mechanical properties of uniform nanofibrous mats with and without ZVI NPs are significantly enhanced even with only 1.0 wt% MWCNTs incorporated. The MWCNT-reinforced PAA/PVA nanofibrous mats containing ZVI NPs (1.6 nm) display excellent capability to decolorize model dyes such as methyl blue, acridine orange, and acid fuchsine with a decoloration percentage of more than 90%. Likewise, the same nanofibrous mats are found to be able to effectively degrade trichloroethylene, a model chlorinated hydrocarbon contaminant, with a degradation efficiency approaching 93%. The MWCNT-reinforced PAA/PVA nanofibrous mats may be used for generating other functionalized nanofiber-based complex materials with enhanced mechanical properties for applications in environmental remediation, catalysis, sensing, and biomedical sciences.

We report a novel electrospun composite nanofiber-based drug delivery system. In this study, halloysite nanotubes (HNTs) were first used to encapsulate a model drug, tetracycline hydrochloride. Then, the drug-loaded HNTs with an optimized encapsulation efficiency were mixed with poly(lactic-co-glycolic acid) (PLGA) polymer for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. In vitro drug release behavior was examined using UV-vis spectroscopy. The biocompatibility of HNT-containing PLGA fibers was evaluated through cell culture and MTT assay. We show that the incorporation of HNTs within the nanofibrous mats does not significantly change the morphology of the mats. In addition, our results indicate that this double-container drug delivery system (both PLGA polymer and HNTs are drug carriers) is beneficial to reduce the burst release of the drug and the introduction of HNTs can significantly improve the tensile strength of the polymer nanofibrous mats. Given the proved biocompatibility of the HNT-containing PLGA nanofibers via MTT assay of cell viability and SEM observation of cell morphology, the drug loaded electrospun composite nanofibrous mats developed in this study may find various applications in tissue engineering and pharmaceutical sciences.

A facile approach that combines the electrospinning technique and layer-by-layer (LbL) assembly method has been developed to synthesize and immobilize zero-valent iron nanoparticles (ZVI NPs) onto the surface of nanofibers for potential environmental applications. In this approach, negatively charged cellulose acetate (CA) nanofibers fabricated by electrospinning CA solution were modified with bilayers composed of positively charged poly(diallyl-dimethyl-ammoniumchloride) (PDADMAC) and negatively charged poly(acrylic acid) (PAA) through electrostatic LbL assembly approach to form composite nanofibrous mats. The composite nanofibrous mats were immersed into the ferrous iron solution to allow Fe(II) ions to complex with the free carboxyl groups of PAA, and then ZVI NPs were immobilized onto the composite nanofibrous mats instantly by reducing the ferrous cations. Combined scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and thermogravimetry analysis demonstrated that the ZVI NPs are successfully synthesized and uniformly distributed into the polyelectrolyte (PE) multilayer films assembled onto the CA nanofibers. The present approach to synthesis ZVI NPs opens a new avenue to fabricating various materials with high surface area for environmental, catalytic, and sensing applications.