<p>Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect ? a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly applied to various agents. Findings from our research can potentially widen the therapeutic window of chemotherapy combinations by emphasizing investigations of optimal drug ratios rather than maximum drug doses and by identifying appropriate nanoparticles for their delivery. Application of these concepts can ultimately help capture the full therapeutic potential of combination regimens.

<p> Manipulation of single cells and particles is important to biology and nanotechnology. Our electrokinetic (EK) tweezers manipulate objects in simple microfluidic devices using gentle fluid and electric forces under vision-based feedback control. In this dissertation, I detail a user-friendly implementation of EK tweezers that allows users to select, position, and assemble cells and nanoparticles. This EK system was used to measure attachment forces between living breast cancer cells, trap single quantum dots with 45 nm accuracy, build nanophotonic circuits, and scan optical properties of nanowires. With a novel multi-layer microfluidic device, EK was also used to guide single microspheres along complex 3D trajectories. The schemes, software, and methods developed here can be used in many settings to precisely manipulate most visible objects, assemble objects into useful structures, and improve the function of lab-on-a-chip microfluidic systems.</p>

published_or_final_version / abstract / Physics / Master / Master of Philosophy

published_or_final_version / abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy

published_or_final_version / Physics / Master / Master of Philosophy

published_or_final_version / abstract / Physics / Master / Master of Philosophy

No description available.

No description available.

<p>The development of finely dispersed powders and superfine-grained materials intended for application in various areas of science and engineering is one of the challenges facing modern nanotechnology. Thus, specific fundamental and applied research was required in order to consolidate advancement made in preparing nano- and submicron crystalline composite materials.</p> <p><br /> Useful templates for electrochemical deposition of nanowires include porous alumina films formed by anodic oxidation of aluminium, nuclear track-etched porous membranes, nanochannel array-glass and mesoporous channel hosts. The properties of the nanowires are directly related to the properties of the nanoporous templates such as, the relative pore orientations in the assembly, the pore size distribution, and the surface roughness of the pores. The template synthesis method, based on the use of porous polymeric and inorganic matrixes, is now actively used for synthesis of such composite materials. The method allows the chemical and/or electrochemical synthesis of nano- and microstructured tubes and wires consisting of conducting polymers, metals and semiconductors.</p> <p><br /> In this study various technological challenges relating to template synthesis and development of nickel nano- and microstructures on adequately strong and durable substrates were investigated. The two methods used were the electrochemical and chemical deposition. &ldquo / Hard nickel&rdquo / bath solution was used for optimal nickel deposition. This optimization included investigating variables such as the template structure, type of electrolyte and form of electrolytic deposition. Scanning Electron Microscopy was used to investigate the structures of template matrixes and the resultant materials. The cyclic voltammetry method was applied for the analysis of electrochemical properties and hydrogen evaluation reaction of nano- and microstructured nickel based electrodes. The activity of composite nano- and microstructured materials in various configurations resulting from pore filling of template matrices by nickel was explored. Studies of the physical structure and chemical properties of the nanostructured materials included investigating the necessary parameters of template matrices. The optimum conditions of synthesis, which allowed development of materials with the highest catalytic activity, were determined.&nbsp / The effect of the template structure on microcrystallinity of the catalyst particles was established using the XRD method. Different new types of non-commercial asymmetric ion track membranes has been tested for nanostructure preparation. The catalytic activity of the new developed nanomaterials is higher as compared to materials using commercial templates. The procedures to modify the newly developed nickel catalyst with Pt, Pd and Pt-Pd alloy have been developed. The Pt and Pt-Pd alloy containing catalyst showed the best performance in water electrolysis. In this work, the promising role for specific application of the new materials in hydrogen economy has been demonstrated.</p>