Synthesis and Testing of Modular Dual-Modality Nanoparticles for Magnetic Resonance and Multispectral Photoacoustic Imaging.

Magnetic resonance (MR) and photoacoustic (PA) imaging are currently being investigated as complementing strategies for applications requiring sensitive detection of cells in vivo. While combined MR/PAI detection of cells requires biocompatible cell labeling probes, water-based synthesis of dual-modality MR/PAI probes presents significant technical challenges. Here we describe facile synthesis and characterization of hybrid modular dextran-stabilized gold/iron oxide (Au-IO) multimetallic nanoparticles (NP) enabling multimodal imaging of cells. The stable association between the IO and gold NP was achieved by priming the surface of dextran-coated IO with silver NP resulting from silver(I) reduction by aldehyde groups, which are naturally present within the dextran coating of IO at the level of 19-23 groups/particle. The Au-IO NP formed in the presence of silver-primed Au-IO were stabilized by using partially thiolated MPEG5-gPLL graft copolymer carrying residual amino groups. This stabilizer served as a carrier of near-infrared fluorophores (e.g., IRDye 800RS) for multispectral PA imaging. Dual modality imaging experiments performed in capillary phantoms of purified Au-IO-800RS NPs showed that these NPs were detectible using 3T MRI at a concentration of 25 µM iron. PA imaging achieved approximately 2.5-times higher detection sensitivity due to strong PA signal emissions at 530 and 770 nm, corresponding to gold plasmons and IRDye integrated into the coating of the hybrid NPs, respectively, with no "bleaching" of PA signal. MDA-MB-231 cells prelabeled with Au-IO-800RS retained plasma membrane integrity and were detectable by using both MR and dual-wavelength PA at 49 ± 3 cells/imaging voxel. We believe that modular assembly of multimetallic NPs shows promise for imaging analysis of engineered cells and tissues with high resolution and sensitivity.

Caseinate-coated zein nanoparticles as potential delivery vehicles for guavinoside B from guava: Molecular interactions and encapsulation properties.

Guavinoside B (GUB) is a characteristic constituent from guava with strong antioxidant activity; however, its low water solubility limits its utilization. Herein, we investigated the interaction between GUB and zein, a prolamin with self-assembling property, using multiple spectroscopic methods and fabricated GUB-zein-NaCas nanoparticles (GUB-Z-N NPs) via the antisolvent coprecipitation approach. GUB caused fluorescence quenching to zein via the static quenching mechanism. Fourier-transform infrared spectroscopy and computational analysis revealed that GUB bound to zein via van der Waals interaction, hydrogen bond, and hydrophobic forces. The GUB-Z-N NPs were in the nanometric size range (< 200 nm) and exhibited promising encapsulation efficiency and redispersibility after freeze-drying. These particles remained stable for up to 31 days at 4 °C and great resistance to salt and pH variation, and displayed superior antioxidant activity to native GUB. The current study highlights the potential of zein-based nanoparticles as delivery vehicles for GUB in the food industry.

Metal-organic frameworks with phosphotungstate incorporated for hydrolytic cleavage of a DNA-model phosphodiester.

Five phosphotungstate-incorporated metal-organic frameworks {[Eu(4)(dpdo)(9)(H(2)O)(16)PW(12)O(40)]}(PW(12)O(40))(2)·(dpdo)(3)·Cl(3) (1); {ZnNa(2)(µ-OH)(dpdo)(4)(H(2)O)(4)[PW(12)O(40)]}·3H(2)O (2); {Zn(3)(dpdo)(7)}[PW(12)O(40)](2)·3H(2)O (3); and [Ln(2)H(µ-O)(2)(dpdo)(4)(H(2)O)(2)][PW(12)O(40)]·3H(2)O (Ln = Ho for 4 and Yb for 5) (dpdo = 4,4'-bipyridine-N,N'-dioxide) have been synthesized through a one-step hydrothermal reaction and characterized by elemental analyses, infrared (IR) spectroscopy, photoluminescence, and single-crystal X-ray diffraction (XRD). The structural analyses indicate that 1-5 display diversity structure from one-dimensional (1D) to three-dimensional (3D) series of hybrids. Kinetic experiments for the hydrolytic cleavage of DNA-model phosphodiester BNPP (bis(p-nitrophenyl)phosphate) were followed spectrophotometrically for the absorbance increase at 400 nm in EPPS (4-(2-hydroxyethyl)piperazine-1-propane sulfonic acid) buffer solution, because of the formation of p-nitrophenoxide with 1-5 under conditions of pH 4.0 and 50 °C. Ultraviolet (UV) spectroscopy indicate that the cleavage of the phosphodiester bond proceeds with the pseudo-first-order rate constant in the range of 10(-7)-10(-6) s(-1), giving an inorganic phosphate and p-nitrophenol as the final products of hydrolysis. The results demonstrate that 1-5 have good catalytic activity and reusability for hydrolytic cleavage of BNPP.

Wheat germ agglutinin-conjugated fluorescent pH sensors for visualizing proton fluxes.

Small-molecule fluorescent wheat germ agglutinin (WGA) conjugates are routinely used to demarcate mammalian plasma membranes, because they bind to the cell's glycocalyx. Here, we describe the derivatization of WGA with a pH-sensitive rhodamine fluorophore (pHRho; pKa = 7) to detect proton channel fluxes and extracellular proton accumulation and depletion from primary cells. We found that WGA-pHRho labeling was uniform and did not appreciably alter the voltage gating of glycosylated ion channels, and the extracellular changes in pH correlated with proton channel activity. Using single-plane illumination techniques, WGA-pHRho was used to detect spatiotemporal differences in proton accumulation and depletion over the extracellular surface of cardiomyocytes, astrocytes, and neurons. Because WGA can be derivatized with any small-molecule fluorescent ion sensor, WGA conjugates should prove useful to visualize most electrogenic and nonelectrogenic events on the extracellular side of the plasma membrane.

The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death.

Nutrient availability influences the production and degradation of materials that are required for cell growth and survival. Autophagy is a nutrient-regulated process that is used to degrade cytoplasmic materials and has been associated with human diseases. Solute transporters influence nutrient availability and sensing, yet we know little about how transporters influence autophagy. Here, we screen for solute transporters that are required for autophagy-dependent cell death and identify CG11665/hermes. We show that hermes is required for both autophagy during steroid-triggered salivary gland cell death and TNF-induced non-apoptotic eye cell death. hermes encodes a proton-coupled monocarboxylate transporter that preferentially transports pyruvate over lactate. mTOR signaling is elevated in hermes mutant cells, and decreased mTOR function suppresses the hermes salivary gland cell death phenotype. Hermes is most similar to human SLC16A11, a protein that was recently implicated in type 2 diabetes, thus providing a link between pyruvate, mTOR, autophagy, and possibly metabolic disorders.

Fluorescent Visualization of Cellular Proton Fluxes.

Cells use plasma membrane proton fluxes to maintain cytoplasmic and extracellular pH and to mediate the co-transport of metabolites and ions. Because proton-coupled transport often involves movement of multiple substrates, traditional electrical measurements provide limited information about proton transport at the cell surface. Here we visualize voltage-dependent proton fluxes over the entire landscape of a cell by covalently attaching small-molecule fluorescent pH sensors to the cell's glycocalyx. We found that the extracellularly facing sensors enable real-time detection of proton accumulation and depletion at the plasma membrane, providing an indirect readout of channel and transporter activity that correlated with whole-cell proton current. Moreover, the proton wavefront emanating from one cell was readily visible as it crossed over nearby cells. Given that any small-molecule fluorescent sensor can be covalently attached to a cell's glycocalyx, our approach is readily adaptable to visualize most electrogenic and non-electrogenic transport events at the plasma membrane.

Post-modification of a MOF through a fluorescent-labeling technology for the selective sensing and adsorption of Ag+ in aqueous solution.

A new approach inspired by fluorescent labeling technology to fluorescently functionalize MOFs via post-modification is reported. A fluorescein-containing MOF FITC@BTPY-NH(2) was synthesized for selective sensing and adsorption of Ag(+) in aqueous solution.

Metal-organic polyhedra containing 36 and 24 folds of amide groups for selective luminescent recognition of natural disaccharides.

An octa-nuclear bicoronal Ce-based triangular prism and tetra-nuclear molecular tetrahedron containing 36 and 24 folds amides within their main backbones were achieved and structurally characterized for the selective luminescent recognition of lactose and sucrose, respectively, over other related natural mono- and disaccharides.