Stimuli-responsive nanomaterials for controlled delivery by light, magnetic and electrical triggers

The use of nanomaterials for biomedical applications is an emerging and important field. This is particularly true of advancements in targeted and controlled drug delivery, which offer several important improvements over traditional drug administration. The clinical efficacy of small-molecule therapeutics is currently limited by many factors, including: poor solubility, inefficient cellular uptake, overly rapid renal clearance and an inability to target only desired locations such as diseased tissues. The use of nanocarriers for drug delivery may greatly improve the efficacy over traditional therapeutics by lowering the total dosage, limiting the exposure to affected areas only, and giving greater temporal control over drug elution. These materials often make use of both organic and inorganic components, exploiting the unique and useful properties of each constituent to achieve novel, synergistic functions. This dissertation presents a study of nanocomposites comprising the three most important materials in this field: titania, iron oxides and polypyrrole. Titania is a strong photocatalyst, iron oxides provide useful responses to applied magnetic fields, and polypyrrole is a polymer with unique electrochemical properties. Studies in this dissertation were aimed at combining these three materials to create a novel structure that is responsive towards light, magnetic fields and electrical stimulation to serve as an enabling platform for the loading and release of biologically interesting compounds. These nanomaterials have been paired with amino acids L-lysine and L-glutamic acid, two organic molecules of interest due to their ability to bind to DNA and proteins, and to form prodrugs that exhibit enhanced performance compared to traditionally administered medicines. Two model compounds have been loaded and released on these carriers: Ketoprofen, an important anti-inflammatory that is traditionally hindered by its limited cellular uptake levels; and fluorescein isothiocyanate, a fluorescent dye molecule that is a common tool used in this field for nanocarrier location and easy visualisation of release-related kinetics. First, an investigation into the effect of pH on the binding of amino acids to titania, iron oxide and polypyrrole is presented with a view towards optimising the functionalised material for subsequent loading and release of the model drugs (in this case, amine-reactive molecules). The release mechanism of photo-activated TiO2 is studied in detail with a particular focus on the competition between the cleavage of bonds versus organic degradation on the catalyst’s surface. Both mechanisms are currently reported in literature and studies were aimed at identifying the more dominant pathway in the system developed alongside understanding the crucial role of reaction time scales on this photochemistry. Then, the pH-tuneable flocculation of the amino acid-functionalised nanoparticles via electrostatic attractions is exploited to create a novel, anisotropic assembly of iron oxides. These filaments display a dynamic and unique response towards a rotating magnetic field by creating local microscale vortices. This motion is used to enhance local delivery rate of molecules through magnetic-field triggered microscale mixing. Finally, this anisotropic iron oxide structure is combined with polypyrrole to create a unique, novel material that possesses directional conductivity, a photothermal response, and magnetic field-triggered release of loaded molecules at enhanced and controllable rates compared with traditional diffusion-limited systems

Classification and construction of interacting fractonic higher-order topological phases

The notion of higher-order topological phases can have interesting generalizations to systems with subsystem symmetries that exhibit fractonic dynamics for charged excitations. In this work, we systematically study the higher-order topological phases protected by a combination of subsystem symmetries and ordinary global symmetries in two and three-dimensional interacting boson systems, with some interacting fermionic examples.Comment: 17 pages, 4 figures with references, comments are welcome

Self-assembly of copper and cobalt complexes with hierarchical size and catalytic properties for hydroxylation of phenol

A feasible and effective self-assembly method to synthesize different scale coordination polymers in highly dilute solution (from nanocrystals to microcrystals and to bulk crystals) without any blocking agent has been described. The growth of crystalline particles was controlled by removing the particles at different reaction times to interrupt the growth at the desired size. The nano and microscale particles show better catalytic conversions and selectivities in the hydroxylation of phenols than the bulk crystals

Bis[bis­(1,10-phenanthroline-κ2 N,N′)copper(I)] μ6-oxido-dodeca­kis-μ2-oxido-hexa­oxidohexa­tungsten(VI)

The title compound, [Cu(C12H8N2)2]2[W6O19], consists of two [Cu(phen)2]+ cations (phen = 1,10-phenanthroline) and one typical [W6O19]2− isopolyanion. The CuI atom is coordinated by four N atoms from two bidentate chelating phen ligands in a distorted tetra­hedral geometry. The hexa­tungstate anion, lying on an inversion center and possessing the well known Lindqvist structure, is formed by six edge-sharing WO6 octa­hedra, thus exhibiting an approximate Oh symmetry. Three kinds of O atoms exist in the hexa­tungstate, viz. terminal Oa, bridging Ob and central Oc atoms. Besides the electrostatic effects between the anions and cations, weak C—H⋯O hydrogen bonds exist between the phen ligands and Oa or Ob atoms. The mean inter­planar distances of 3.485 (1) and 3.344 (1) Å indicate π–π stacking inter­actions between neighboring phen ligands. These weak hydrogen bonds and π–π stacking inter­actions lead to a two-dimensional network

Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

Electroacupuncture (EA) has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36) and Kunlun (BL60) acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001). The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression