In the assembly of DNA nanostructures, the specificity of Watson-Crick base pairing is used to control matter at the nanoscale. Using this technology for drug delivery is a promising route toward the magic bullet concept, as it would allow the realization of complex assemblies that co-localize drugs, targeting ligands and other functionalities in one nanostructure. Anthracyclines' mechanism of action in cancer therapy is to intercalate DNA, and since DNA nanotechnology allows for such a high degree of customization, we hypothesized that this would allow us to tune the DNA nanostructures for optimal delivery of the anthracycline doxorubicin (Dox) to human breast cancer cells. We have tested two DNA origami nanostructures on three different breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7). The different nanostructures were designed to exhibit varying degrees of global twist, leading to different amounts of relaxation in the DNA double-helix structure. By tuning the nanostructure design we are able to (i) tune the encapsulation efficiency and the release rate of the drug and (ii) increase the cytotoxicity and lower the intracellular elimination rate when compared to free Dox. Enhanced apoptosis induced by the delivery system in breast cancer cells was investigated using flow cytometry. The findings indicate that DNA origami nanostructures represent an efficient delivery system for Dox, resulting in high degrees of internalization and increased induction of programmed cell death in breast cancer cells. In addition, by designing the structures to exhibit different degrees of twist, we are able to rationally control and tailor the drug release kinetics.

A thin film technology compatible with multilayer device fabrication is critical for exploring the potential of the 39-K superconductor magnesium diboride for superconducting electronics. Using a Hybrid Physical-Chemical Vapor Deposition (HPCVD) process, it is shown that the high Mg vapor pressure necessary to keep the MgB 2 phase thermodynamically stable can be achieved for the in situ growth of MgB 2 thin films. The films grow epitaxially on (0001) sapphire and (0001) 4H-SiC substrates and show a bulk-like T c of 39 K, a J c (4.2K) of 1.2 × 10 7 A/cm 2 in zero field, and a H c2 (0) of 29.2 T in parallel magnetic field. The surface is smooth with a root-mean-square roughness of 2.5 nm for MgB 2 films on SiC. This deposition method opens tremendous opportunities for superconducting electronics using MgB 2 .

We have used two polytypes of silicon carbide single crystals, 4H-SiC and 6H-SiC, as the substrates for MgB 2 thin films grown by hybrid physical-chemical vapor deposition ͑HPCVD͒. The c-cut surface of both polytypes has a hexagonal lattice that matches closely with that of MgB 2. Thermodynamic calculations indicate that SiC is chemically stable under the in situ deposition conditions for MgB 2 using HPCVD. The MgB 2 films on both polytypes show high-quality epitaxy with a Rutherford backscattering channeling yield of 12%. They have T c above 40 K, low resistivities, high residual resistivity ratios, and high critical current densities. The results demonstrate that SiC is an ideal substrate for MgB 2 thin films.

We have epitaxially grown Ba0.6Sr0.4TiO3 (BST-0.4) thin films on MgO(001) substrates. By inserting a very thin Ba1−xSrxTiO3 (x=0.1–0.7) interlayer between the MgO substrate and the main layer of BST-0.4, we are able to manipulate the degree of the stress in BST-0.4 films. We have controlled the stress states, i.e., the lattice distortion ratio (D=in-plane lattice constant/out-of-plane lattice constant) of the BST-0.4 films by varying the chemical composition of the interlayers. We have found that small variations of D value can result in significantly large changes of dielectric properties. A BST-0.4 film under small tensile stress, which has a D value of 1.0023, shows the largest dielectric permittivity and tunability.

Resistance to single or multiple chemotherapeutic drugs is a major complication in clinical oncology and is one of the most common treatment limitations in patients with reoccurring cancers. Nanoparticle (NP)-based drug delivery systems (DDS's) have been shown to overcome drug resistance in cancer cells mainly by avoiding the activation of efflux pumps in these cells. We demonstrate in this work that polyester-based hyperbranched dendritic-linear (HBDL)-based NPs carrying doxorubicin (Dox) can effectively overcome microsomal glutathione transferase 1 (MGST1)-mediated drug resistance in breast cancer cells. Our DDS was much more effective at considerably lower intracellular Dox concentrations (IC50 6.3 μm vs. 36.3 μm) and achieved significantly greater reductions in viability and induced higher degrees of apoptosis (31% vs. 14%) compared to the free drug in the resistant cells. Dox-loaded HBDL NPs were found to translocate across the membranes of resistant cells via active endocytic pathways and to be transported to lysosomes, mitochondria, and the endoplasmic reticulum. A significantly lower amount of Dox accumulated in these cytoplasmic compartments in resistant cells treated with free Dox. Moreover, we found that Dox-HBDL significantly decreased the expression of MGST1 and enhanced mitochondria-mediated apoptotic cell death compared to free Dox. Dox-HBDL also markedly activated the JNK pathway that contributes to the apoptosis of drug-resistant cells. These results suggest that HBDL NPs can modulate subcellular drug distribution by specific endocytic and trafficking pathways and that this results in drug delivery that alters enzyme levels and cellular signaling pathways and, most importantly, increases the induction of apoptosis. Our findings suggest that by exploiting the cell transport machinery we can optimize the polymeric vehicles for controlled drug release to overcome drug resistance combat drug resistance with much higher efficacy.

The high resistivity of many bulk and film samples of MgB 2 is most readily explained by the suggestion that only a fraction of the cross-sectional area of the samples is effectively carrying current. Hence the supercurrent (J c ) in such samples will be limited by the same area factor, arising for example from porosity or from insulating oxides present at the grain boundaries. We suggest that a correlation should exist, J c ~ 1/∆ρ 300-50K , where ∆ρ 300-50K is the change in the apparent resistivity from 300 K to 50 K. We report measurements of ρ(T) and J c for a number of films made by hybrid physical-chemical vapor deposition which demonstrate this correlation, although the "reduced effective area" argument alone is not sufficient. We suggest that this argument can also apply to many polycrystalline bulk and wire samples of MgB 2 .

Dendrimers and their less well-defined cousins, hyperbranched polymers, are widely investigated as scaffold materials in tissue engineering, as drug delivery agents, and in diagnostic imaging applications. Despite the large interest of using these unique materials as polymer-based nanoparticles in biomedical applications, a clear understanding of the cellular uptake and transport of these polyester-based nanoparticles is still lacking. The objective of this study is to evaluate the cellular uptake profiles and intracellular trafficking of polymer micelles built from the hyperbranched polyester Boltorn, fitted with poly(ethylene glycol) and fluorescent groups in MDA-MB468 breast cancer cells. Results show that the uptake of these nanoparticles correlated positively to both time and concentration, and that the uptake of the nanoparticles was energy dependent. These polyesterbased nanoparticles appear to translocate across cells via clathrin- and macropinocytosis-mediated endocytosis. Observations of the intracellular trafficking of the nanoparticles indicate that particles could be released from early endosomes after being internalized, and the particles exhibit perinuclear localization. The uptake behavior of the nanoparticles was further evaluated in a range of cell lines. These results allow the generation of the knowledge base required to design polyester-based nanocarriers that can be used efficiently and specifically for drug delivery applications and imaging applications.

Histamine functionalized poly(allyl glycidyl ether)-b-poly(ethylene glycol)-b-poly(allyl glycidyl ether) (PAGE-PEO-PAGE) triblock copolymers represent a new class of physically cross-linked, pH-responsive hydrogels with significant potential for biomedical applications. These telechelic triblock copolymers exhibited abrupt and reversible hydrogelation above pH 7.0 due to a hudrophilic/hydrophobic transition of the histamine units to form a network of hydrophobic domains bridged by a hydrophilic PEO matrix. These hydrophobic domains displayed improved ordering upon increasing pH and self-assembled into a body centered cubic lattice at pH 8.0, while at lower concentrations formed well-defined micelles. Significantly, all materials were found to be non-toxic when evaluated on three different cell lines and suggests a range of medical and biomedical applications.