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The development of nanoformulations with simple compositions that can exert targeted combination therapy still remains a great challenge in the area of precision cancer nanomedicine. Herein, we report the design of a multifunctional nanoplatform based on methotrexate (MTX)-loaded layered double hydroxide (LDH) coated with chlorin e6 (Ce6)-modified MCF-7 cell membranes (CMM) for combined chemo/sonodynamic therapy of breast cancer. LDH nanoparticles were in situ loaded with MTX via coprecipitation, and coated with CMM that were finally functionalized with phospholipid-modified Ce6. The created nanoformulation of LDH-MTX@CMM-Ce6 displays good colloidal stability under physiological conditions and can release MTX in a pH-dependent manner. We show that the formulation can homologously target breast cancer cells, and induce their significant apoptosis through arresting the cell cycle via cooperative MTX-based chemotherapy and ultrasound (US)-activated sonodynamic therapy. The assistance of US can not only trigger sonosensitizer Ce6 to produce reactive oxygen species, but also enhance the cellular uptake of LDH-MTX@CMM-Ce6 via an acoustic cavitation effect. Upon intravenous injection and US irradiation, LDH-MTX@CMM-Ce6 displays an admirable antitumor performance towards a xenografted breast tumor mouse model. Furthermore, the modification of Ce6 on the CMM endows the LDH-based nanoplatform with fluorescence imaging capability. The developed LDH-based nanoformulation here provides a general intelligent cancer nanomedicine platform with simple composition and homologous targeting specificity for combined chemo/sonodynamic therapy and fluorescence imaging of tumors. [ABSTRACT FROM AUTHOR]

We present the development of indocyanine green (ICG)-loaded and folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs) as a versatile nanoplatform for targeted dual-mode fluorescence (FL)/ photoacoustic (PA) imaging, and photothermal therapy (PTT)/photodynamic therapy (PDT) of tumors in vivo. In this study, acid-treated MWCNTs with carboxyl residues were first covalently conjugated with polyethyleneimine (PEI). This was followed by sequential modification of FA via a polyethylene glycol (PEG) segment, fluorescein isothiocyanate (FITC), and succinic anhydride (SAH), multifunctional FA-modified MWCNTs (MWCNT--PEI·SAH--FITC--PEG--FA) were formed. The functional MWCNTs possess exceptional colloidal stability, good hemocompatibility/cytocompatibility in a studied concentration range, and targeting specificity to FA receptor-overexpressing cancerous cells. Via π-π stacking interactions, the MWCNTs enable highly efficient loading of ICG and the ICG-loaded MWCNTs exhibit excellent photostability and can be used for FL imaging/PDT of tumors due to the singlet oxygen (¹O2) generation from ICG. In addition, the near-infrared absorption characteristic of ICG also renders the MWCNT nanoplatform with a capacity for simultaneous PA imaging and PTT of tumors. Our study reports a novel theranostic nanosystem that can be used for targeted dual-mode FL/PA imaging and PTT/PDT of tumors in vivo, which may show profound promise for translation into clinical uses. [ABSTRACT FROM AUTHOR]

Background: Improved methods for the early and specific detection of ovarian cancer are needed. Methods: In this experimental study, we used folic acid (FA)-targeted iron oxide (Fe3O4) nanoparticles (NPs) as a T2-negative contrast agent for magnetic resonance (MR) imaging to accurately detect ovarian cancer tissues in an intraperitoneal xenograft tumor model. Human serous ovarian cell line (Skov-3), with over expressed FA receptors, was chosen as the targeted tumor cell mode. For in vivo experiments, the cells were injected intraperitoneally into nude mice to produce intraabdominal ovarian cancers. FA-targeted and non-targeted Fe3O4 NPs were prepared. Results: FA-targeted Fe3O4 NPs with a mean size of 9.2 ± 1.7 nm have a negligible cytotoxicity to human serous ovarian cell line (Skov-3). Importantly, the results of cellular uptake suggested that FA-targeted Fe3O4 NPs have a targeting specificity to Skov-3 cells overexpressing FA receptors. FA-targeted Fe3O4 NPs could be specifically localized by magnetic resonance (MR) imaging to the intraperitoneal human ovarian carcinoma tissues, as documented by a statistically significant difference (p = 0.002, n = 3) in T2 signal intensities of xenograft tumor tissues when injected with FA-targeted and non-targeted Fe3O4 NPs at 4 h post-injection. Conclusion: FA-targeted Fe3O4 NPs appear to be promising agents for the detection of human ovarian carcinoma by MR imaging, and possibly also for the hyperthermal treatment of the tumors. [ABSTRACT FROM AUTHOR]

Cancer cell metastasis causes 90% of cancer patient death. Detection and targeted capture of cancer cells in vitro are of paramount importance. The development of novel nanodevices for cancer cell capture applications, however, still remains a great challenge. Here we report a facile approach to fabricating multifunctional dendrimer-modified electrospun cellulose acetate (CA) nanofibers for targeted cancer cell capture applications. In this study, hydrolyzed electrospun CA nanofibers with negative surface charge were assembled layer-by-layer with a bilayer of poly(diallyldimethylammonium chloride) (PDADMAC) and polyacrylic acid (PAA) via electrostatic interactions. Thereafter, amine-terminated generation 5 poly(amidoamine) dendrimers pre-modified with folic acid (FA) and fluorescein isothiocyanate were covalently conjugated onto the bilayer-assembled nanofibers via the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride coupling reaction, followed by acetylation to neutralize the remaining dendrimer surface amines. The formation of electrospun CA nanofibers, assembly of the PDADMAC/PAA bilayer onto the CA nanofibers, and the dendrimer modification on the nanofibers were characterized via different techniques. The formed dendrimer-modified CA nanofibers were then used to capture cancer cells overexpressing FA receptors. We show that the bilayer self-assembly and the subsequent dendrimer modification do not appreciably change the fiber morphology. Importantly, the modification of FA-targeted multifunctional dendrimers renders the CA nanofibers with superior capability to specifically capture cancer cells (KB cells, a model cancer cell line) overexpressing high-affinity FA receptors. The approach to modifying electrospun nanofibers with multifunctional dendrimers may be extended to fabricate other functional nanodevices for capturing different types of cancer cells. [ABSTRACT FROM AUTHOR]

We report here an effective approach to modifying laponite (LAP) nanodisks with folic acid (FA) for targeted anticancer drug delivery applications. In this approach, LAP nanodisks were first modified with 3-aminopropyldimethylethoxysilane (APMES) to render them with abundant surface amines, followed by conjugation with FA via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) chemistry. The formed FA-modified LAP nanodisks (LM-FA) were then used to encapsulate anticancer drug doxorubicin (DOX). The surface modification of LAP nanodisks and the subsequent drug encapsulation within the LAP nanodisks were characterized via different techniques. We show that the LM-FA is able to encapsulate DOX with an efficiency of 92.1 ± 2.2%, and the formed LM-FA/DOX complexes are able to release DOX in a pH-dependent manner with a higher DOX release rate under acidic pH conditions than under physiological pH conditions. The encapsulation of DOX within LM-FA does not compromise its therapeutic activity. Importantly, the formed LM-FA/DOX complexes are able to specifically target cancer cells overexpressing high-affinity FA receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and exert specific therapeutic efficacy to the target cancer cells. The developed FA-modified LAP nanodisks may hold great promise to be used as an efficient nanoplatform for targeted delivery of different anticancer drugs. [ABSTRACT FROM AUTHOR]

We report a facile approach to synthesizing 3-aminopropyltrimethoxysilane (APTS)-coated magnetic iron oxide (Fe3O4@APTS) nanoparticles (NPs) with tunable surface functional groups for potential biomedical applications. The Fe3O4 NPs with a mean diameter of 6.5 nm were synthesized by a hydrothermal route in the presence of APTS. The formed amine-surfaced Fe3O4@APTS NPs were further chemically modified with acetic anhydride and succinic anhydride to generate neutral (Fe3O4@APTS.Ac) and negatively charged (Fe3O4@APTS.SAH) NPs. These differently functionalized NPs were extensively characterized by x-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetry analysis, zeta potential measurements, and T2 relaxometry. The cytotoxicity of the particles was evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide colorimetric viability assay of cells along with microscopic observation of cell morphology. The hemocompatibility of the particles was assessed by in vitro hemolysis assay. We show that the hydrothermal approach enables an efficient modification of APTS onto the Fe3O4 NP surfaces and the formed NPs with different surface charge polarities are water-dispersible and colloidally stable. The acetylated Fe3O4@APTS.Ac NPs displayed good biocompatibility and hemocompatibility in the concentration range of 0-100 &mgr;g ml-1, while the pristine Fe3O4@APTS and Fe3O4@APTS.SAH particles started to display slight cytotoxicity at a concentration of 10 &mgr;g ml-1. The findings from this study suggest that the Fe3O4@APTS NPs synthesized by the one-pot hydrothermal route can be surface modified for various potential biomedical applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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?m 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 ?g/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. [ABSTRACT FROM AUTHOR]

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) viaan 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. [ABSTRACT FROM AUTHOR]

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 viabinding 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. [ABSTRACT FROM AUTHOR]

Functionalized dendrimer‐entrapped gold nanoparticles (Au DENPs) are of scientific and technological interest in biomedical applications. In this study, Au DENPs prepared with amine‐terminated generation 5 (G5) poly(amido amine) dendrimers as templates were subjected to acetylation to neutralize the positive surface charge of the particles. By varying the molar ratio of Au salt to G5 dendrimer, we prepared acetylated Au DENPs with a size range of 2–4 nm. Meanwhile, we attempted to add glucose to the dialysis liquid of the acetylated Au DENPs to prevent possible particle aggregation after lyophilization. The acetylated Au DENPs with different compositions (Au salt/dendrimer molar ratios) were characterized with 1H‐NMR, transmission electron microscopy, ultraviolet–visible (UV–vis) spectrometry, and ζ‐potential measurements. We show that when the molar ratio of Au salt to dendrimer was equal to or larger than 75:1, the acetylated Au DENPs showed a significant aggregation after lyophilization, and the addition of glucose was able to preserve the colloidal stability of the particles. X‐ray absorption measurements showed that the attenuation of the acetylated Au DENPs was much higher than that of the iodine‐based contrast agent at the same molar concentration of the active element (Au vs iodine). In addition, the acetylated Au DENPs enabled X‐ray computed tomography (CT) imaging of mice after intravenous injection of the particles. These findings suggest a great potential for acetylated Au DENPs as a promising contrast agent for CT imaging applications. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

We report the fabrication of water-stable electrospun polyethyleneimine (PEI)/polyvinyl alcohol (PVA) nanofibers that have super dye sorption capability. Electrospinning parameters including flow rate, applied voltage, and polymer concentration were optimized to obtain smooth and uniform PEI/PVA nanofibers. The nanofibers with a mean diameter of 490 ± 83 nm can be rendered water insoluble viacrosslinking using glutaraldehyde vapor. The formed nanofibers with a smooth and uniform morphology before and after crosslinking were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical property testing. The sorption capability of the PEI/PVA nanofibers was confirmed by UV-vis spectrometry. We show that the water-stable nanofibrous mats can effectively absorb methyl blue, which is a typical dye used in the printing and dyeing industry. The dye sorption kinetics and isotherm follow the pseudo-second-order model and the Langmuir model, respectively. The developed polymer nanofiber system has a great potential in decolorizing dyeing wastewater for environmental remediation applications. [ABSTRACT FROM AUTHOR]

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 vitrodrug 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 viaMTT 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

The article presents a multi-ethnic atherosclerosis study which investigates the contribution of residential environments in Type 2 diabetes mellitus incidents. It examines the physical activities and healthy diets of neighborhood resources which can lessen diabetes incidents. It adds that people who live in worse environments have lower risk factors and are less associated with the disease. It concludes that health promotion and modification of physical environment should be improved.

This study investigated associations between neighborhood physical and social environments and body mass index in 2,865 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) aged 45–84 years and residing in Maryland, New York, and North Carolina. Neighborhood (census tract) environments were measured in non-MESA participants residing in MESA neighborhoods (2000–2002). The neighborhood physical environment score combined measures of a better walking environment and greater availability of healthy foods. The neighborhood social environment score combined measures of greater aesthetic quality, safety, and social cohesion and less violent crime. Marginal maximum likelihood was used to estimate associations between neighborhood environments and body mass index (kg/m2) before and after adjustment for individual-level covariates. MESA residents of neighborhoods with better physical environments had lower body mass index (mean difference per standard deviation higher neighborhood measure = −2.38 (95% confidence interval (CI): −3.38, −1.38) kg/m2 for women and −1.20 (95% CI: −1.84, −0.57) kg/m2 for men), independent of age, race/ethnicity, education, and income. Attenuation of these associations after adjustment for diet and physical activity suggests a mediating role of these behaviors. In men, the mean body mass index was higher in areas with better social environments (mean difference = 0.52 (95% CI: 0.07, 0.97) kg/m2). Improvement in the neighborhood physical environment should be considered for its contribution to reducing obesity. [ABSTRACT FROM AUTHOR]