Dendrimer-Assisted Formation of Fe3O4/Au Nanocomposite Particles for Targeted Dual Mode CT/MR Imaging of Tumors.

A unique dendrimer-assisted approach is reported to create Fe3O4/Au nanocomposite particles (NCPs) for targeted dual mode computed tomography/magnetic resonance (CT/MR) imaging of tumors. In this approach, preformed Fe3O4 nanoparticles (NPs) are assembled with multilayers of poly(γ-glutamic acid) (PGA)/poly(L-lysine)/PGA/folic acid (FA)-modified dendrimer-entrapped gold nanoparticles via a layer-by-layer self-assembly technique. The interlayers are crosslinked via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chemistry, the assembled Au core NPs are then used as seed particles for subsequent seed-mediated growth of Au shells via iterative Au salt reduction process, and subsequent acetylation of the remaining amines of dendrimers leads to the formation of Fe3O4/Au(n.)Ac-FA NCPs with a tunable molar ratio of Au/Fe3O4. It is shown that the Fe3O4/Au(n.)Ac-FA NCPs at an optimized Au/Fe3O4 molar ratio of 2.02 display a relatively high R2 relaxivity (92.67 × 10(-3) M(-1) s(-1)) and good X-ray attenuation property, and are cytocompatible and hemocompatible in the given concentration range. Importantly, with the FA-mediated targeting, the Fe3O4/Au(n.)Ac-FA NCPs are able to be specifically uptaken by cancer cells overexpressing FA receptors, and be used as an efficient nanoprobe for targeted dual mode CT/MR imaging of a xenografted tumor model. With the versatile dendrimer chemistry, the developed Fe3O4/Au NCPs may be differently functionalized, thereby providing a unique platform for diagnosis and therapy of different biological systems.

Improving the electrochemical energy conversion of solid oxide fuel cells through the interface effect in La0.6Sr0.4Co0.2Fe0.8O3-δ-BaTiO3-δ electrolyte.

Herein, we present a heterostructure electrolyte with considerable potential for application in low-temperature solid oxide fuel cells (LT-SOFCs). Heterostructure electrolytes are advantageous because the multiphase interfaces in their heterostructures are superior for ion conduction than for bulk conduction. Most previous studies on heterostructure electrolytes explained the influence of interfacial parameters on ion conduction in terms of the space charge zones and lattice mismatch, neglecting the characterization of the interface. In this study, a series of heterostructure electrolytes comprising La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) and BaTiO3-δ (BTO) with different composition ratios was developed. Further, the lattice mismatch due to thermal stress in this system was evaluated by thermal expansion and electron energy loss spectroscopy (EELS) analyses. Results indicated that 7LSCF-3BTO produced the narrowest interface and the most surface oxygen vacancies, suggesting that the stress generated by thermal expansion increased the density of the interface. The cell with the optimal 7LSCF-3BTO composition delivered a peak power density of 910mW cm-2 and an open circuit voltage of 1.07 V at 550 °C. The heterojunction effect was studied to elucidate the prevention of short circuiting in the LSCF-BTO cell, considering the Femi level and barrier energy height. This study provides novel ideas for the design of electrolytes for LT-SOFCs from the interface perspective.

Facile one-pot preparation, surface functionalization, and toxicity assay of APTS-coated iron oxide nanoparticles.

We report a facile approach to synthesizing 3-aminopropyltrimethoxysilane (APTS)-coated magnetic iron oxide (Fe(3)O(4)@APTS) nanoparticles (NPs) with tunable surface functional groups for potential biomedical applications. The Fe(3)O(4) NPs with a mean diameter of 6.5 nm were synthesized by a hydrothermal route in the presence of APTS. The formed amine-surfaced Fe(3)O(4)@APTS NPs were further chemically modified with acetic anhydride and succinic anhydride to generate neutral (Fe(3)O(4)@APTS⋅Ac) and negatively charged (Fe(3)O(4)@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 T(2) 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 Fe(3)O(4) NP surfaces and the formed NPs with different surface charge polarities are water-dispersible and colloidally stable. The acetylated Fe(3)O(4)@APTS⋅Ac NPs displayed good biocompatibility and hemocompatibility in the concentration range of 0-100 µg ml(-1), while the pristine Fe(3)O(4)@APTS and Fe(3)O(4)@APTS⋅SAH particles started to display slight cytotoxicity at a concentration of 10 µg ml(-1). The findings from this study suggest that the Fe(3)O(4)@APTS NPs synthesized by the one-pot hydrothermal route can be surface modified for various potential biomedical applications.

Designing High Interfacial Conduction beyond Bulk via Engineering the Semiconductor-Ionic Heterostructure CeO2-δ/BaZr0.8Y0.2O3 for Superior Proton Conductive Fuel Cell and Water Electrolysis Applications.

Proton ceramic fuel cells (PCFCs) are an emerging clean energy technology; however, a key challenge persists in improving the electrolyte proton conductivity, e.g., around 10-3-10-2 S cm-1 at 600 °C for the well-known BaZr0.8Y0.2O3 (BZY), that is far below the required 0.1 S cm-1. Herein, we report an approach for tuning BZY from low bulk to high interfacial conduction by introducing a semiconductor CeO2-δ forming a semiconductor-ionic heterostructure CeO2-δ/BZY. The interfacial conduction was identified by a significantly higher conductivity obtained from the BZY grain boundary than that of the bulk and a further improvement from the CeO2-δ/BZY which achieved a remarkably high proton conductivity of 0.23 S cm-1. This enabled a high peak power of 845 mW cm-2 at 520 °C from a PCFC using the CeO2-δ/BZY as the electrolyte, in strong contrast to the BZY bulk conduction electrolyte with only 229 mW cm-2. Furthermore, the CeO2-δ/BZY fuel cell was operated under water electrolysis mode, exhibiting a very high current density output of 3.2 A cm-2 corresponding to a high H2 production rate, under 2.0 V at 520 °C. The band structure and a built-in-field-assisted proton transport mechanism have been proposed and explained. This work demonstrates an efficient way of tuning the electrolyte from low bulk to high interfacial proton conduction to attain sufficient conductivity required for PCFCs, electrolyzers, and other advanced electrochemical energy technologies.

Facile synthesis of folic acid-functionalized iron oxide nanoparticles with ultrahigh relaxivity for targeted tumor MR imaging.

We present the polyethyleneimine (PEI)-assisted synthesis of folic acid (FA)-functionalized iron oxide (Fe3O4) nanoparticles (NPs) with ultrahigh relaxivity for in vivo targeted tumor magnetic resonance (MR) imaging. In this work, water-dispersible and stable Fe3O4 NPs were synthesized in the presence of PEI via a facile mild reduction approach. The surface PEI coating afforded the formed Fe3O4 NPs with the ability to be functionalized with polyethylene glycol (PEG)-linked FA and fluorescein isothiocyanate (FI). A further acetylation step to neutralize the remaining PEI surface amines gave rise to the formation of multifunctional FA-functionalized Fe3O4 NPs, which were subsequently characterized via different methods. We show that the developed FA-functionalized Fe3O4 NPs have a good water-dispersibility, good colloidal stability, ultrahigh r2 relaxivity (475.92 mM-1 s-1), and good hemocompatibility and cytocompatibility in the studied concentration range. The targeting specificity of the FA-modified Fe3O4 NPs to FA receptor (FAR)-overexpressing HeLa cells (a human cervical carcinoma cell line) was subsequently validated by flow cytometry and confocal microscopy. Significantly, the developed FA-modified Fe3O4 NPs can be used as a nanoprobe for targeted MR imaging of HeLa cells in vitro and the xenografted tumor model in vivo via an active FA-mediated targeting strategy. The developed multifunctional FA-modified Fe3O4 NPs with an ultrahigh r2 relaxivity may be used as an efficient nanoprobe for the targeted MR imaging of various kinds of FAR-overexpressing tumors.

Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MR imaging.

We report a polyethyleneimine (PEI)-mediated approach to synthesizing hyaluronic acid (HA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo targeted tumor magnetic resonance (MR) imaging applications. In this work, Fe3O4 NPs stabilized by PEI were first synthesized via a one-pot hydrothermal method. The formed PEI-stabilized Fe3O4 NPs were then modified with fluorescein isothiocyanate (FI) and HA with two different molecular weights to obtain two different Fe3O4 NPs (Fe3O4-PEI-FI-HA6K and Fe3O4-PEI-FI-HA31K NPs) with a size of 15-16 nm. The formed HA-modified multifunctional Fe3O4 NPs were characterized via different techniques. We show that the multifunctional Fe3O4 NPs are water-dispersible and colloidal stable in different aqueous media. In vitro cell viability and hemolysis studies reveal that the particles are quite cytocompatible and hemocompatible in the given concentration range. Furthermore, confocal microscopy and flow cytometry data demonstrate that HA-targeted Fe3O4 NPs are able to be uptaken specifically by cancer cells overexpressing CD44 receptors, and be used as efficient probes for targeted MR imaging of cancer cells in vitro and xenografted tumor models in vivo. With the tunable amine-based conjugation chemistry, the PEI-stabilized Fe3O4 NPs may be functionalized with other biological ligands or drugs for diagnosis and therapy of different biological systems.

Targeted and pH-responsive delivery of doxorubicin to cancer cells using multifunctional dendrimer-modified multi-walled carbon nanotubes.

We report the use of multifunctional dendrimer-modified multi-walled carbon nanotubes (MWCNTs) for targeted and pH-responsive delivery of doxorubicin (DOX) into cancer cells. In this study, amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) were covalently linked to acid-treated MWCNTs, followed by acetylation of the remaining dendrimer terminal amines to neutralize the positive surface potential. The formed multifunctional MWCNTs (MWCNT/G5.NHAc-FI-FA) were characterized via different techniques. Then, the MWCNT/G5.NHAc-FI-FA was used to load DOX for targeted and pH-responsive delivery to cancer cells overexpressing high-affinity folic acid receptors (FAR). We showed that the MWCNT/G5.NHAc-FI-FA enabled a high drug payload and encapsulation efficiency both up to 97.8% and the formed DOX/MWCNT/G5.NHAc-FI-FA complexes displayed a pH-responsive release property with fast DOX release under acidic environment and slow release at physiological pH conditions. Importantly, the DOX/MWCNT/G5.NHAc-FI-FA complexes displayed effective therapeutic efficacy, similar to that of free DOX, and were able to target to cancer cells overexpressing high-affinity FAR and effectively inhibit the growth of the cancer cells. The synthesized multifunctional dendrimer-modified MWCNTs may be used as a targeted and pH-responsive delivery system for targeting therapy of different types of cancer cells.

Facile one-pot synthesis of Fe3O4@Au composite nanoparticles for dual-mode MR/CT imaging applications.

A facile one-pot hydrothermal approach to synthesizing Fe3O4@Au composite nanoparticles (CNPs) for dual-mode magnetic resonance (MR) and computed tomography (CT) imaging applications is reported. In this work, polyethyleneimine (PEI) partially modified with poly(ethylene glycol) monomethyl ether (mPEG) was used as a stabilizer to form gold NPs (mPEG-PEI.NH2-Au NPs) with the assistance of sodium borohydride reduction. The mPEG-PEI.NH2-Au NPs were then mixed with iron(II) salt in a basic aqueous solution followed by treatment under an elevated temperature and pressure. This hydrothermal process led to the formation of Fe3O4@Au-mPEG-PEI.NH2 CNPs. The remaining PEI amine groups were finally acetylated to reduce the surface positive charge of the CNPs. The formed Fe3O4@Au-mPEG-PEI.NHAc (Fe3O4@Au) CNPs were characterized via different techniques. The combined in vitro cell viability assay, cell morphology observation, flow cytometry, and hemolysis assay data show that the formed Fe3O4@Au CNPs are noncytotoxic and hemocompatible in the given concentration range. MR and CT imaging data reveal that the formed Fe3O4@Au CNPs have a relatively high r2 relaxivity (146.07 mM(-1) s(-1)) and good X-ray attenuation property, which enables their uses as contrast agents for MR imaging of mouse liver and CT imaging of rat liver and aorta. The Fe3O4@Au CNPs developed via the facile one-pot approach may have promising potential for the dual-mode MR/CT imaging of different biological systems.

Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging.

We report a facile polyethyleneimine (PEI)-mediated approach to synthesizing folic acid (FA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo magnetic resonance (MR) imaging of tumors. In this study, stable PEI-coated Fe3O4 NPs were prepared by a one-pot hydrothermal route. The aminated Fe3O4 NPs with PEI coating enabled covalent conjugation of fluorescein isothiocyanate (FI) and folate-conjugated polyethylene glycol (PEG) with one end of carboxyl groups (FA-PEG-COOH). Followed by final acetylation, FA-targeted PEGylated Fe3O4 NPs (Fe3O4-PEI-Ac-FI-PEG-FA NPs) were formed. The formed multifunctional Fe3O4 NPs were characterized via different techniques. We show that the PEI-mediated approach along with the PEGylation conjugation enables the generation of water-dispersible and stable multifunctional Fe3O4 NPs, and the particles are quite cytocompatible and hemocompatible in the given concentration range as confirmed by in vitro cytotoxicity assay, cell morphology observation, and hemolysis assay. In addition, flow cytometry and confocal microscopy data show that the multifunctional Fe3O4 NPs are able to target a model cancer cell line (KB cells) overexpressing FA receptors in vitro. Importantly, the FA-targeted Fe3O4 NPs are able to be used as an efficient nanoprobe for MR imaging of cancer cells in vitro and a xenografted tumor model in vivo via an active FA targeting pathway. With the facile PEI-mediated formation strategy and PEGylation conjugation chemistry, the Fe3O4 NPs may be multifunctionalized with other biological ligands for MR imaging of different biological systems.

Facile hydrothermal synthesis and surface functionalization of polyethyleneimine-coated iron oxide nanoparticles for biomedical applications.

We report the facile hydrothermal synthesis and surface functionalization of branched polyethyleneimine (PEI)-coated iron oxide nanoparticles (Fe3O4-PEI NPs) for biomedical applications. In this study, Fe3O4-PEI NPs were synthesized via a one-pot hydrothermal method in the presence of PEI. The formed Fe3O4-PEI NPs with primary amine groups on the surface were able to be further functionalized with polyethylene glycol (PEG), acetic anhydride, and succinic anhydride, respectively. The formed pristine and functionalized Fe3O4-PEI NPs were characterized via different techniques. We showed that the sizes of the Fe3O4-PEI NPs were able to be controlled by varying the mass ratio of Fe(II) salt and PEI. In addition, the formed Fe3O4-PEI NPs with different surface functionalities had good water dispersibility, colloidal stability, and relatively high R2 relaxivity (130-160 1/(mM·s)). Cell viability assay data revealed that the surface PEGylation and acylation of Fe3O4-PEI NPs rendered them with good biocompatibility in the given concentration range, while the pristine aminated Fe3O4-PEI NPs started to display slight toxicity at the concentration of 50 µg/mL. Importantly, macrophage cellular uptake results demonstrated that both PEGylation and acetylation of Fe3O4-PEI NPs were able to significantly reduce the nonspecific macrophage uptake, likely rendering the particles with prolonged circulation time. With the proven hemocompatibility and rich amine conjugation chemistry, the Fe3O4-PEI NPs with different surface functionalities may be applied for various biomedical applications, especially for magnetic resonance imaging and therapy.

Carbon nanotube-incorporated multilayered cellulose acetate nanofibers for tissue engineering applications.

We report the fabrication of a novel carbon nanotube-containing nanofibrous polysaccharide scaffolding material via the combination of electrospinning and layer-by-layer (LbL) self-assembly techniques for tissue engineering applications. In this approach, electrospun cellulose acetate (CA) nanofibers were assembled with positively charged chitosan (CS) and negatively charged multiwalled carbon nanotubes (MWCNTs) or sodium alginate (ALG) via a LbL technique. We show that the 3-dimensional fibrous structures of the CA nanofibers do not appreciably change after the multilayered assembly process except that the surface of the fibers became much rougher than that before assembly. The incorporation of MWCNTs in the multilayered CA fibrous scaffolds tends to endow the fibers with improved mechanical property and promote fibroblast attachment, spreading, and proliferation when compared with CS/ALG multilayer-assembled fibrous scaffolds. The approach to engineering the nanofiber surfaces via LbL assembly likely provides many opportunities for new scaffolding materials design in various tissue engineering applications.

Multifunctional dendrimer-entrapped gold nanoparticles for dual mode CT/MR imaging applications.

We report the synthesis, characterization, and utilization of gadolium-loaded dendrimer-entrapped gold nanoparticles (Gd-Au DENPs) for dual mode computed tomography (CT)/magnetic resonance (MR) imaging applications. In this study, amine-terminated generation five poly(amidoamine) dendrimers (G5.NH2) modified with gadolinium (Gd) chelator and polyethylene glycol (PEG) monomethyl ether were used as templates to synthesize gold nanoparticles (AuNPs). Followed by sequential chelation of Gd(III) and acetylation of the remaining dendrimer terminal amine groups, multifunctional Gd-Au DENPs were formed. The formed Gd-Au DENPs were characterized via different techniques. We show that the formed Gd-Au DENPs are colloidally stable and non-cytotoxic at an Au concentration up to 50 µM. With the coexistence of two radiodense imaging elements of AuNPs and Gd(III) within one NP system, the formed Gd-Au DENPs display both r1 relaxivity for MR imaging mode and X-ray attenuation property for CT imaging mode, which enables CT/MR dual mode imaging of the heart, liver, kidney, and bladder of rat or mouse within a time frame of 45 min. Furthermore, in vivo biodistribution studies reveal that the Gd-Au DENPs have an extended blood circulation time and can be cleared from the major organs within 24 h. The strategy to use facile dendrimer technology to design dual mode contrast agents may be extended to prepare multifunctional platforms for targeted multimode molecular imaging of various biological systems.

Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles.

We report the synthesis and characterization of folic acid (FA)-modified multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) for targeted dual mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) modified with Gd(III) chelator, polyethylene glycol (PEG) monomethyl ether, and PEGylated FA were used as templates to entrap gold nanoparticles (AuNPs). Further chelation of Gd(III) ions and acetylation of the remaining dendrimer terminal amines led to the formation of multifunctional FA-targeted Au DENPs loaded with Gd(III) (Gd-Au DENPs-FA). The formed Gd-Au DENPs-FA probes were characterized via different techniques. We show that the Gd-Au DENPs-FA probes with an Au NP core size of 4.0 nm are water dispersible, stable under different pH and temperature conditions, and cytocompatible in the given concentration range. With the co-existence of AuNPs and Gd(III) ions within the single multifunctional particles, Gd-Au DENPs-FA displayed high X-ray attenuation intensity and reasonable r1 relaxivity. These properties of the particles enabled them to be used as dual mode nanoprobes for targeted CT/MR imaging of cancer cells in vitro and xenograft tumor model in vivo via FA receptor-mediated active targeting pathway. The strategy to design multifunctional nanoprobes using the versatile dendrimer nanotechnology may be extended to design various dual mode or multimode imaging agents for accurate diagnosis of different types of cancer.