Respiratory dysfunction is a major cause of death in people with spinal cord injury (SCI). A remaining unsolved problem in treating SCI is the intolerable side effects of the drugs to patients. In a significant departure from conventional targeted nanotherapeutics to overcome the blood−brain barrier (BBB), this work pursues a drug-delivery approach that uses neural tracing retrograde transport proteins to bypass the BBB and deliver an adenosine A1 receptor antagonist drug, 1,3-dipropyl-8-cyclopentyl xanthine, exclusively to the respiratory motoneurons in the spinal cord and the brainstem. A single intradiaphragmatic injection at one thousandth of the native drug dosage induces prolonged respiratory recovery in a hemisection animal model. To translate the discovery into new treatments for respiratory dysfunction, we carry out this study to characterize the purity and quality of synthesis, stability, and drug-release properties of the neural tracing protein (wheat germ agglutinin chemically conjugated to horseradish peroxidase)-coupled nanoconjugate. We show that the batch-to-batch particle size and drug dosage variations are less than 10%. We evaluate the nanoconjugate size against the spatial constraints imposed by transsynaptic transport from pre to postsynaptic neurons. We determine that the nanoconjugate formulation is capable of sustained drug release lasting for days at physiologic pH, a prerequisite for long-distance transport of the drug from the diaphragm muscle to the brainstem. We model the drug-release profiles using a first-order reaction model and the Noyes−Whitney diffusion model. We confirm via biological electron microscopy that the nanoconjugate particles do not accumulate in the tissues at the injection site. We define the nanoconjugate storage conditions after monitoring the solution dispersion stability under various conditions for 4 months. This study supports further development of neural tracing protein-enabled nanotherapeutics for treating respiratory problems associated with SCI.
Three-dimensional magnetic Fe1.3Ni0.7P nanorod assemblies (gels and aerogels) were prepared by oxidation of Fe1.3Ni0.7P nanorods capped with 11-mercaptoundecanoic acid (MUA) and 1-dodecanethiol (DDT), and their magnetic properties were evaluated in comparison to discrete nanorod precursors and in the context of the interfacial chemical characteristics associated with the ligand group employed. Treatment of MUA- and DDT-capped Fe1.3Ni0.7P nanorods with hydrogen peroxide results in gels that largely retain the structural (as assessed by powder X-ray diffraction) and morphological (as revealed by transmission electron microscopy) features of the nanorods in a pore–matter integrated network. However, aerogels created from MUA-capped particles undergo dispersion upon treatment with ethylenediaminetetraacetic acid (EDTA), whereas those produced from DDT-capped particles remain unchanged. Likewise, reductive annealing resulted in cleavage of the aerogel produced from DDT-capped particles, whereas the aerogels produced from MUA-capped particles remained intact, if more compact, as reflected in a ca. 50% decrease in surface area. The data are consistent with distinct interfacial chemistry in the two networks: amorphous phosphite/phosphate olation linkages in aerogels produced from DDT-capped particles vs a combination of phosphite/phosphate olation linkages and metal-ion cross-linking of pendant carboxylates in aerogels produced from MUA-capped particles. The superparamagnetic blocking temperature (T B) of discrete Fe1.3Ni0.7P nanoparticles, and the aerogels made from 11-MUA and 1-DDT exchanged nanoparticles, all appear in the range 30–40 K, and the field-dependent magnetization profiles (M–H) exhibit minimal hysteresis at 50 K with coercivity (H C) values ∼10 Oe. Thus, the Fe1.3Ni0.7 x P nanoparticles comprising the aerogel network behave independently, as expected for a disordered 3-D assembly, and the magnetic aerogels can be regarded as a summation of their individual components.
Novel synthetic route to synthesize solution-phase anisotropic MnSb nanoparticles was developed and the solution–solid–solid growth mechanism was elucidated.
A solution phase methodology was developed for the formation of discrete colloidal MnSb nanoparticles using dimanganesedecacarbonyl and triphenylantimony as the main reaction components. Stoichiometric reactions result in significant Sb impurities, but these can be eliminated by the use of excess Mn reagent, limiting the reaction time, and using a lower temperature (280 °C) relative to that commonly employed for MnP or MnAs synthesis (330-360 °C). The resultant MnSb nanoparticles are, when evidenced by both powder X-ray diffraction and transmission electron microscopy, ca. 14 nm in diameter and exhibit low polydispersity (13±1.7 nm). High Angle Annular Dark Field-Scanning Transmission Electron Microscopy and energy dispersive line scan data revealed that the as-synthesized MnSb nanoparticles are coreshell in nature, having a MnSb core and an amorphous manganese oxide shell. Evidence is presented supporting a pathway for decomposition of MnSb nanoparticles driven by formation of MnO 2 and Sb due to reaction with adventitious O 2 . The MnSb nanoparticles are superparamagnetic at room temperature, and exhibit suppressed moments attributed to surface oxidation arising from the high surface area and intrinsic oxophilicity of Mn. IntroductionBinary and ternary intermetallic compounds formed by combination of 3d transition metals and pnicogens X (X=P, As, Sb or Bi) are of special interest due to their various electronic and magnetic properties. 1 Among transition metal pnictides, manganese arsenide (MnAs), manganese 15 external magnetic field of 100 Oe. The FC plot shows a gradual increase of molar magnetization with decrease of temperature from 320 K which then saturates at temperatures roughly below 50 K. In the ZFC curve, the sample shows a broad maximum in the range of 245-255 K, near the intersection of the FC with the ZFC curve. Collectively, the above behavior suggests superparamagnetic behavior. Under FC conditions, the magnetic moments of the particles are frozen along the direction of applied magnetic field upon cooling, producing saturation at lowtemperature. In contrast, for ZFC samples, the moments are frozen in random orientation at low temperature, and start to align in the field upon heating, reaching a maximum at the blocking temperature,T B , above which superparamagnetic behavior is exhibited, resulting in a drop in magnetization again. The T B depends on the volume of the nanoparticle, the presence of anisotropy (shape or magnetocrystalline), as well as the time-scale of the measurement (~10 -9 s for DC magnetometry). In the present case the peak corresponding to T B is relatively broad suggesting a distribution of values reflecting the polydispersity of the sample. 38 We attribute the irregularity in both FC and ZFC plots around 43 K to a small leak of oxygen into the sample chamber that makes a condensed film of oxygen, resulting a para-antiferromagnetic transition of oxygen around 43 K. 39
Porous aromatic frameworks (PAFs) are attractive materials for applications where high surface area and material stability govern performance. Most of the highest surface area PAFs are synthesized using poorly scalable...
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