Publications by Year: 2012

2012
K. Y. Yoon, Li, Z. C., Neilson, B. M., Lee, W., Huh, C., Bryant, S. L., Bielawski, C. W., and Johnston, K. P., “Effect of Adsorbed Amphiphilic Copolymers on the Interfacial Activity of Superparamagnetic Nanoclusters and the Emulsification of Oil in Water,” Macromolecules, vol. 45, pp. 5157-5166, 2012. Publisher's VersionAbstract
A series of sub-100 nm superparamagnetic iron oxide nanoparticles with amphiphilic poly(acrylic acid-b-butylacrylate); PAA-b-PBA) copolymer shells were synthesized and characterized by NMR spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and a superconducting quantum interference device (SQUID) to investigate the effect of the polymer structure on the interfacial tension for nanoparticles adsorbed at the dodecane-water interface. Large reductions in interfacial tension of up to 27.6 mN/m were measured at nanoparticle concentrations of 0.27 wt %, indicating significant nanoparticle adsorption and interaction between the oil and water molecules at the interface. The adsorption energy of the polymer-coated nanoparticles at the dodecane/water interface was determined from the interfacial tension and nanoparticle radius, and analyzed in terms of the structure of the polymer stabilizer. Furthermore, the equilibrium adsorption of amphiphilic copolymer-functionalized iron oxide nanoclusters at the oil water interface was determined by material balance from the concentration in the excess water phase and the known overall oil/water interfacial area. The formation and stabilization of oil droplets were on the order of 10 mu m in water with unusually low nanoparticle concentrations was explained in terms of the high interfacial activity of the particles.
T. Y. Wang, Mancuso, J. J., Kazmi, S. M. S., Dwelle, J., Sapozhnikova, V., Willsey, B., Ma, L. L., Qiu, J. Z., Li, X. K., Dunn, A. K., Johnston, K. P., Feldman, M. D., and Milner, T. E., “Combined two-photon luminescence microscopy and OCT for macrophage detection in the hypercholesterolemic rabbit aorta using plasmonic gold nanorose,” Lasers in Surgery and Medicine, vol. 44, pp. 49-59, 2012. Publisher's VersionAbstract
Background and Objectives The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two-channel two-photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta-based macrophages using plasmonic gold nanorose as an imaging contrast agent. Study Design/Materials and Methods: Nanorose uptake by macrophages was identified by TPL microscopy in macrophage cell culture. Ex vivo aorta segments (8 x 8 x 2 mm(3)) rich in macrophages from a rabbit model of aorta inflammation were imaged by TPL microscopy in combination with OCT. Aorta histological sections (5 mm in thickness) were also imaged by TPL microscopy. Results: Merged two-channel TPL images showed the lateral and depth distribution of nanorose-loaded macrophages (confirmed by RAM-11 stain) and other aorta components (e.g., elastin fiber and lipid droplet), suggesting that nanorose-loaded macrophages are diffusively distributed and mostly detected superficially within 20 mm from the luminal surface of the aorta. Moreover, OCT images depicted detailed surface structure of the diseased aorta. Conclusions: Results suggest that TPL microscopy combined with OCT can simultaneously reveal macrophage distribution with respect to aorta surface structure, which has the potential to detect vulnerable plaques and monitor plaque-based macrophages overtime during cardiovascular interventions. Lasers Surg. Med. 44:49-59, 2012. (C) 2012 Wiley Periodicals, Inc.
S. Ryoo, Rahmani, A. R., Yoon, K. Y., Prodanovic, M., Kotsmar, C., Milner, T. E., Johnston, K. P., Bryant, S. L., and Huh, C., “Theoretical and experimental investigation of the motion of multiphase fluids containing paramagnetic nanoparticles in porous media,” Journal of Petroleum Science and Engineering, vol. 81, pp. 129-144, 2012. Publisher's VersionAbstract
Paramagnetic nanoparticles are potentially useful for monitoring of immiscible fluids distribution in subsurface, as they can be induced to move by an imposed magnetic field. The nanoparticles can be designed to be preferentially adsorbed at oil-water interface, as well as to have the long-term dispersion stability with minimal retention in the porous medium to be monitored. When exposed to magnetic field, they generate sufficient interfacial movements for external detection. When paramagnetic nanoparticles are either adsorbed at oil-water or air-water interface or dispersed in one of two fluid phases co-existing in pores, and exposed to external magnetic field, the resultant particle movements displace the interface. Interfacial tension acts as a restoring force, leading to interfacial fluctuation and a pressure (sound) wave. Our previous work (Prodanovic et al., 2010) provided a theoretical explanation for the motion of the interface between a suspension of paramagnetic nanorods and a non-magnetized fluid in a cylindrical dish, as measured by phase-sensitive optical coherence tomography (PS-OCT). Here we report on additional experiments carried out with a range of in-house synthesized and surface-modified iron-oxide nanoparticles. We also improved numerical method to be volume conserving for more quantitative matching. The measurements of interfacial motion by PS-OCT reported confirm theoretical predictions of the frequency doubling and the importance of material properties, such as magnetic susceptibility, for the interface displacement. The results are encouraging: this laboratory and modeling study is thus an important step to develop a magnetic field-based method for an accurate, non-invasive determination of multiphase fluids distribution in reservoir rock. With the combined experimental and modeling work, strategies for improved nanoparticle design will be developed so that the interfacial, thereby acoustic, response can be magnified. (C) 2011 Elsevier B.V. All rights reserved.
K. P. Johnston, Maynard, J. A., Truskett, T. M., Borwankar, A. U., Miller, M. A., Wilson, B. K., Dinin, A. K., Khan, T. A., and Kaczorowski, K. J., “Concentrated Dispersions of Equilibrium Protein Nanoclusters That Reversibly Dissociate into Active Monomers,” Acs Nano, vol. 6, pp. 1357-1369, 2012. Publisher's VersionAbstract
Stabilizing proteins at high concentration is of broad interest in drug delivery, for treatment of cancer and many other diseases. Herein, we create highly concentrated antibody dispersions (up to 260 mg/mL) comprising dense equilibrium nanoclusters of protein (monoclonal antibody 1B7, polyclonal sheep immunoglobulin G, and bovine serum albumin) molecules which, upon dilution in vitro or administration in vivo, remain conformationally stable and biologically active. The extremely concentrated environment within the nanoclusters (similar to 700 mg/mL) provides conformational stability to the protein through a novel self-crowding mechanism, as shown by computer simulation, while the primarily repulsive nanocluster interactions result in colloidally stable, transparent dispersions. The nanoclusters are formed by adding trehalose as a cosolute which strengthens the short-ranged attraction between protein molecules. The protein cluster diameter was reversibly tuned from 50 to 300 nm by balancing short-ranged attraction against long-ranged electrostatic repulsion of weakly charged protein at a pH near the isoelectric point. This behavior is described semiquantitatively with a free energy model which includes the fractal dimension of the clusters. Upon dilution of the dispersion in vitro, the clusters rapidly dissociated into fully active protein monomers as shown with biophysical analysis (SEC, DI.S, CD, and SDS-PAGE) and sensitive biological assays. Since the concept of forming nanoclusters by tuning colloid interactions is shown to be general, It is likely applicable to a variety of biological therapeutics, mitigating the need to engineer protein stability through amino acid modification. In vivo subcutaneous Injection into mice results in indistinguishable pharmacokinetics versus a standard antibody solution. Stable protein dispersions with low viscosities may potentially enable patient self-administration by subcutaneous injection of antibody. therapeutics being discovered and developed.
S. J. Yoon, Murthy, A., Johnston, K. P., Sokolov, K. V., and Emelianov, S. Y., “Thermal stability of biodegradable plasmonic nanoclusters in photoacoustic imaging,” Optics Express, vol. 20, pp. 29479-29487, 2012. Publisher's VersionAbstract
The photothermal stability of plasmonic nanoparticles is critically important to perform reliable photoacoustic imaging and photothermal therapy. Recently, biodegradable nanoclusters composed of sub-5 nm primary gold particles and a biodegradable polymer have been reported as clinically-translatable contrast agents for photoacoustic imaging. After cellular internalization, the nanoclusters degrade into 5 nm primary particles for efficient excretion from the body. In this paper, three different sizes of biodegradable nanoclusters were synthesized and the optical properties and photothermal stability of the nanoclusters were investigated and compared to that of gold nanorods. The results of our study indicate that 40 nm and 80 nm biodegradable nanoclusters demonstrate higher photothermal stability compared to gold nanorods. Furthermore, 40 nm nanoclusters produce higher photoacoustic signal than gold nanorods at a given concentration of gold. Therefore, the biodegradable plasmonic nanoclusters can be effectively used for photoacoustic imaging and photothermal therapy. (C) 2012 Optical Society of America
M. N. Patel, Wang, X. Q., Slanac, D. A., Ferrer, D. A., Dai, S., Johnston, K. P., and Stevenson, K. J., “High pseudocapacitance of MnO2 nanoparticles in graphitic disordered mesoporous carbon at high scan rates,” Journal of Materials Chemistry, vol. 22, pp. 3160-3169, 2012. Publisher's VersionAbstract
Nanocomposites composed of MnO2 and graphitic disordered mesoporous carbon (MnO2/C) were synthesized for high total specific capacitance and redox pseudocapacitance (C-MnO2) at high scan rates up to 200 mV s(-1). High resolution transmission electron microscopy (HRTEM) with energy dispersive X-ray spectroscopy (EDX) demonstrated that MnO2 nanodomains were highly dispersed throughout the mesoporous carbon structure. According to HRTEM and X-ray diffraction (XRD), the MnO2 domains are shown to be primarily amorphous and less than 5 nm in size. For these composites in aqueous 1 M Na2SO4 electrolyte, C-MnO2 reached 500 F/g(MnO2) at 2 mV s(-1) for 8.8 wt% MnO2. A capacitance fade of only 20% over a 100-fold change in scan rate was observed for a high loading of 35 wt% MnO2 with a C-MnO2 of 310 F/g(MnO2) at the highest scan rate of 200 mV s(-1). The high electronic conductivity of the graphitic 3D disordered mesoporous carbon support in conjunction with the thin MnO2 nanodomains facilitate rapid electron and ion transport offering the potential of improved high power density energy storage pseudocapacitors.
M. A. Miller, Khan, T. A., Kaczorowski, K. J., Wilson, B. K., Dinin, A. K., Borwankar, A. U., Rodrigues, M. A., Truskett, T. M., Johnston, K. P., and Maynard, J. A., “Antibody nanoparticle dispersions formed with mixtures of crowding molecules retain activity and In Vivo bioavailability,” Journal of Pharmaceutical Sciences, vol. 101, pp. 3763-3778, 2012. Publisher's VersionAbstract
Monoclonal antibodies continue to command a large market for treatment of a variety of diseases. In many cases, the doses required for therapeutic efficacy are large, limiting options for antibody delivery and administration. We report a novel formulation strategy based on dispersions of antibody nanoclusters that allows for subcutaneous injection of highly concentrated antibody (similar to 190?mg/mL). A solution of monoclonal antibody 1B7 was rapidly frozen and lyophilized using a novel spiral-wound in-situ freezing technology to generate amorphous particles. Upon gentle stirring, a translucent dispersion of approximately 430?nm protein clusters with low apparent viscosity (similar to 24?cp) formed rapidly in buffer containing the pharmaceutically acceptable crowding agents such as trehalose, polyethylene glycol, and n-methyl-2-pyrrolidone. Upon in vitro dilution of the dispersion, the nanoclusters rapidly reverted to monomeric protein with full activity, as monitored by dynamic light scattering and antigen binding. When administered to mice as an intravenous solution, subcutaneous solution, or subcutaneous dispersion at similar (4.67.3?mg/kg) or ultra-high dosages (51.6?mg/kg), the distribution and elimination kinetics were within error and the protein retained full activity. Overall, this method of generating high-concentration, low-viscosity dispersions of antibody nanoclusters could lead to improved administration and patient compliance, providing new opportunities for the biotechnology industry. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:37633778, 2012
D. A. Slanac, Lie, A., Paulson, J. A., Stevenson, K. J., and Johnston, K. P., “Bifunctional Catalysts for Alkaline Oxygen Reduction Reaction via Promotion of Ligand and Ensemble Effects at Ag/MnOx Nanodomains,” Journal of Physical Chemistry C, vol. 116, pp. 11032-11039, 2012. Publisher's VersionAbstract
Achieving synergy between inexpensive metals and metal oxides is a key challenge for the development of highly active, economical catalysts. We report the synthesis and characterization of a highly active oxygen reduction reaction(ORR) catalyst composed of Ag particles (3 nm) in intimate contact with thin (similar to 1 nm) MnOx domains on Vulcan carbon (VC) as shown via electron microscopy. A new electroless co-deposition scheme, whereby MnO4- ions are reduced by carbon, formed nanosized MnOx reduction centers for Ag nanoparticle deposition. A bifunctional mechanism for ORR is proposed, in which the HO2- intermediate is formed electrochemically and is regenerated via disproportionation into OH- and O-2. A 3x mass activity enhancement is observed for Ag-MnOx/VC (125 mA/mg(Ag+MnOx)) over the linear combination of pure component activities using rotating disk voltammetry. The Ag-MnOx/VC mass activity is comparable to commercial Pd/VC (111 inA/rng(Pd)) and Pt/VC (136 mA/mg(Pt)). Furthermore, the number of electrons transferred for ORR reaches 3.5 for Ag-MnOx, higher than for MnOx (2.8) and close to the full four-electron ORR. The synergy can be rationalized by ensemble effects, where Ag and MnOx domains facilitate the formation and disproportionation of HO2-, respectively, and ligand effects from the unique electronic interaction at the Ag-MnOx interface.
T. H. A. Nguyen, Islam, M. T., Park, J. M., Gal, Y. S., Johnston, K. P., and Lim, K. T., “Crystal growth of gold nanoparticles through annealing induced phase transition of semifluorinated block copolymer micellar films,” Materials Letters, vol. 75, pp. 111-114, 2012. Publisher's VersionAbstract
The preparation of gold nanoparticles incorporated in self-assembled and ordered semifluorinated poly(ethylene oxide)-b-poly(1H,1H-dihydroperfluorooctyl methacrylate) (PEO-b-PFOMA) thin films was explored through annealing induced phase transition. The micellar thin films containing gold nanoparticles whose average size was dependent on the block length of the copolymer were produced by spin casting the solution of PEO10k-b-PFOMA(12k) and PEO20k-b-PFOMA(22k) in chloroform with a gold precursor, LiAuCl4. Three annealing modes were attempted for the Au-loaded micellar films: solvent vapor annealing, supercritical CO2 at 70 degrees C and thermal annealing at 100 degrees C. The nanoparticles dispersed in PEO regions were forced to follow the morphological change of the PEO phase and grew into larger single particles in PEO domains. The solvent annealing produced higher ordering of Au nanoparticles than scCO(2) or thermal annealing. (C) 2012 Elsevier B.V. All rights reserved.
M. A. Miller, DiNunzio, J., Matteucci, M. E., Ludher, B. S., Williams, R. O., and Johnston, K. P., “Flocculated amorphous itraconazole nanoparticles for enhanced in vitro supersaturation and in vivo bioavailability,” Drug Development and Industrial Pharmacy, vol. 38, pp. 557-570, 2012. Publisher's VersionAbstract
Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug, itraconazole (Itz), was utilized to produce amorphous powders with desirable dissolution properties for high bioavailability in rats. Antisolvent precipitation (AP) was utilized to form Itz nanodispersions with high drug loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive Eudragit (R) L100-55 (EL10055). The HPMC dispersions were flocculated by desolvating the polymer through the addition of a divalent salt, and the enteric EL10055 by reducing the pH. The formation of open flocs by diffusion limited aggregation facilitated redispersion of the flocs at pH 6.8. Upon redispersion of the flocculated nanoparticles at pH 6.8, the particle size was modestly larger than the original size, on the order of 1 mu m. High in vitro supersaturation (AUC) of the flocculated nanoparticle dispersions was observed in micellar media at pH 6.8, after 2 hours initial exposure at pH 1.2 to simulate the stomach, relative to the AUC for a commercially available Itz formulation, Sporanox. Greater in vivo bioavailability in rats was correlated directly to the higher in vitro AUC at pH 6.8 with micelles during the pH shift experiment for the flocculated nanoparticle dispersions relative to Sporanox. The ability to generate and sustain high supersaturation in micellar media at pH 6.8, as shown with the in vitro pH shift dissolution test, is beneficial for increasing bioavailability of Itz by oral delivery.
D. A. Slanac, Li, L., Mayoral, A., Yacaman, M. J., Manthiram, A., Stevenson, K. J., and Johnston, K. P., “Atomic resolution structural insights into PdPt nanoparticle-carbon interactions for the design of highly active and stable electrocatalysts,” Electrochimica Acta, vol. 64, pp. 35-45, 2012. Publisher's VersionAbstract
Interfacial interactions between sub-4 nm metal alloy nanoparticles and carbon supports, although not well understood at the atomic level, may be expected to have a profound influence on catalytic properties. Pd3Pt2 alloy particles comprised of a disordered surface layer over a corrugated crystalline core are shown to exhibit strong interfacial interactions with a similar to 20-50 nm spherical carbon support, as characterized by probe aberration corrected scanning transmission electron microscopy (pcSTEM). The disordered shells were formed from defects introduced by Pd during arrested growth synthesis of the alloy nanoparticles. The chemical and morphological changes in the catalyst, before and after cyclic stability testing (1000 cycles, 0.5-1.2V). were probed with cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and pcSTEM. The strong metal-support interaction, along with the uniform alloy structure raised the mass activity by a factor of 1.8 versus pure Pt. The metal-support interactions also mitigated nanoparticle coalescence, dissolution, and ripening, resulting in only a 20% loss in mass activity (versus 60% for pure Pt on carbon) after the cyclic stability test. The design of alloy structure, guided by insight from atomic scale pcSTEM, for enhanced catalytic activity and stability, resulting from strong wetting with a deformable disordered shell, has the potential to be a general paradigm for improving catalytic performance. (C) 2011 Elsevier Ltd. All rights reserved.
T. Y. Wang, Mancuso, J. J., Sapozhnikova, V., Dwelle, J., Ma, L. L., Willsey, B., Kazmi, S. M. S., Qiu, J. Z., Li, X. K., Asmis, R., Johnston, K. P., Feldman, M. D., and Milner, T. E., “Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles,” Journal of Biomedical Optics, vol. 17, 2012. Publisher's VersionAbstract
The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P < 0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P < 0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.036009]
D. A. Slanac, Hardin, W. G., Johnston, K. P., and Stevenson, K. J., “Atomic Ensemble and Electronic Effects in Ag-Rich AgPd Nanoalloy Catalysts for Oxygen Reduction in Alkaline Media,” Journal of the American Chemical Society, vol. 134, pp. 9812-9819, 2012. Publisher's VersionAbstract
The ability to design and characterize uniform, bimetallic alloy nanoparticles, where the less active metal enhances the activity of the more active metal, would be of broad interest in catalysis. Herein, we demonstrate that simultaneous reduction of Ag and Pd precursors provides uniform, Ag-rich AgPd alloy nanoparticles (similar to 5 nm) with high activities for the oxygen reduction reaction (ORR) in alkaline media. The particles are crystalline and uniformly alloyed, as shown by X-ray diffraction and probe corrected scanning transmission electron microscopy. The ORR mass activity per total metal was 60% higher for the AgPd2 alloy relative to pure Pd. The mass activities were 2.7 and 3.2 times higher for Ag9Pd (340 mA/mg(metal)) and Ag4Pd (598 mA/mg(metal)), respectively, than those expected for a linear combination of mass activities of Ag (60 mA/mg(Ag)) and Pd (799 mA/mg(Pd)) particles, based on rotating disk voltammetry. Moreover, these synergy factors reached 5-fold on a Pd mass basis. For silver-rich alloys (Ag <= 4Pd), the particle surface is shown to contain single Pd atoms surrounded by Ag from cyclic voltammetry and CO stripping measurements. This morphology is favorable for the high activity through a combination of modified electronic structure, as shown by XPS, and ensemble effects, which facilitate the steps of oxygen bond breaking and desorption for the ORR. This concept of tuning the heteroatomic interactions on the surface of small nanoparticles with low concentrations of precious metals for high synergy in catalytic activity may be expected to be applicable to a wide variety of nanoalloys.