Amino-functionalised polystyrene microspheres are promising candidates as delivery systems due to their unique features, tunable surface functionalities, and controllable release of the cargo. Herein several strategies for the conjugation of biologically relevant cargoes to these microspheres and their biological evaluation are described. Firstly, dispersion and suspension polymerisation methods were applied for the synthesis of these devices. Subsequently, these polymeric particles were employed in multistep solid phase synthesis to conjugate a broad range of cargoes. The capability of the resulting constructs to cross the cell membrane and deliver the desired cargo was evaluated by flow cytometry and confocal microscopy. Additionally, the effect of these particles on cell viability was determined. Moreover a chemical strategy for dual fuctionalisation allowed the production of microspheres capable of carrying two cargos simultaneously (e.g. a biologically relevant cargo and a tracking fluorophore). Several strategies were used to transport biomolecules such as peptides and oligonucleotides inside cells. Cell-impermeable peptides with neuroprotective activity were conjugated to microspheres to facilitate their internalisation and they were efficiently delivered into neuroblastom cells (SH-SY5Y) without affecting their therapeutic activity. In addition, several microsphere-mediated oligonucleotide delivery strategies were investigated. As a first approach, siRNA was successfully attached to microspheres via thiol linkage or via electrostatic interaction (by formation of polycationated microspheres-siRNA microplexes). Using both strategies EGFP expression was efficiently down-regulated in cervical cancer cells permanently expressing EGFP (HeLa-EGFP) following beadfection. Additionally embryonic stem (ES) cells were beadfected with siRNA linked to microspheres by amide formation and essential transcription factors implicated in cell renewal and differentiation were successfully silenced, exceeding the silencing capabilities of commercially available lipofection products. Furthermore, a novel approach for the intracellular delivery of plasmid DNA was designed. Following an easy protocol for the linearisation and functionalisation of the plasmid DNA, this was covalently coupled to beads and cells were homogeneously ‘beadfected’. Finally, the coupling of fluorogenic substrates for caspase-3 to microspheres allowed the in situ monitoring and quantification of apoptotic process within cells. In conclusion, these small particles are excellent devices for the efficient intracellular delivery of a broad range of cargoes.

貴金屬納米顆粒催化劑因其獨特的性質而備受關注。他們的高比表面積和可控的形貌使得他們表現出於同類體相材料所不同的催化性能。為了避免催化反應過程中由於納米顆粒本身形貌的改變而引起的催化活性降低，貴金屬納米顆粒通常被負載在固體氧化物載體上。同時，由於協同作用的產生，固體金屬氧化物載體在反應過程中也能對納米顆粒的催化效果產生影響。本論文系統介紹了利用超聲噴霧法製備貴金屬納米顆粒負載的金屬氧化物微納米球的過程，以及為研究這種微纳米球的催化性能而進行的實驗檢測。氧化物存在不仅为催化剂提供了载体，而且其介孔结构亦有利于反应物扩散到纳米催化剂的周围，从而提高反应的速率。 / 本論文首先介紹了一步法製備貴金屬納米顆粒負載的金屬氧化物微纳米球及其在催化反应中的應用。我們選擇了金、鉑和鈀來分別負載在二氧化鈦、二氧化鋯和三氧化二鋁微納米球上。這幾種貴金屬和氧化物都是在環境污染控制、石油化工產業和醫藥產業中具有代表性的催化劑及襯底。除了檢測我們所製備的微納米顆粒的結構形貌等特徵外，我們還利用對硝基苯酚還原為對胺基苯酚的這個催化反應檢驗了這些貴金屬納米顆粒負載的氧化物微納米球的催化活性。考慮到三種貴金屬和三種氧化物的排列組合，以及金屬含量可能產生的影響，我們準備了九類共18份樣品，逐個進行催化反應。最後的結果顯示，含鈀0.1%摩爾比例的二氧化鈦表現出最強的催化活性。同时，這種方法也可以推廣到其他的貴金屬以及氧化物襯底，從而可以簡單方便地製備各种氧化物负载貴金屬催化劑，并可以對他們之間的協同作用進行研究。 / 此外，我根據同樣的超聲噴霧法製備了貴金屬負載的空心介孔氧化物微納米球。這個研究課題引入了聚苯乙烯球作為模板。同時利用聚苯乙烯球表面修飾過的金屬納米顆粒之间的相互作用，實現了金屬納米顆粒在球表面的吸附，进而聚苯乙烯球可以作為載體將金屬納米顆粒帶入介孔氧化物中。通過熱分解將聚苯乙烯球除去後，金屬納米顆粒就可以吸附在空心介孔氧化物球的內表面。在這個實驗中，我們先製備好據有特殊形貌的金屬納米顆粒，比如金納米棒、鈀納米立方体和金納米棒外面包覆鈀的納米殼鞘結構。然後借助聚苯乙烯球將其帶入介孔二氧化鈦和二氧化鋯及二氧化硅中。在對硝基苯酚還原的實驗中，这种介孔微纳米球表现出良好的催化性能并在一定程度上提高了催化剂的循环性。 / 为了尽可能的提高催化剂的循环性，我希望能獲得據有良好磁性的介孔微納米球。我們嘗試了兩種方法，一是將磁性納米顆粒比如鐵的氧化物納米顆粒引入介孔氧化物微納米球，另一種方法是製備據有磁性的介孔氧化鐵微納米球。我们相信通過這種方法，貴金屬納米顆粒負載的介孔氧化物微納米球的催化性能，尤其是循環性能必然會顯著的提高。 / Noble metal nanoparticles/nanocrystals have attracted much attention as catalysts due to their unique characteristics, including high surface areas and well-controlled facets, which are not often possessed by their bulk counterparts. To avoid the loss of their catalytic activities brought about by their size and shape changes during catalytic reactions, noble metal nanoparticles/nanocrystals are usually dispersed and supported finely on solid oxide supports to prevent agglomeration, nanoparticle growth, and therefore the decrease in the total surface area. Moreover, metal oxide supports can also play important roles in catalytic reactions through the synergistic interactions with loaded metal nanoparticles/nanocrystals. In this thesis, I use ultrasonic aerosol spray to produce hybrid microspheres that are composed of noble metal nanoparticles/nanocrystals embedded in mesoporous metal oxide matrices. The mesoporous metal oxide structure allows for the fast diffusion of reactants and products as well as confining and supporting noble metal nanoparticles. / I will first describe my studies on noble metal-loaded mesoporous oxide microspheres as catalysts. Three types of noble metals (Au, Pt, Pd) and three types of metal oxide substrates (TiO₂, ZrO₂, Al₂O₃) were selected, because they are widely used for practical catalytic applications involved in environmental cleaning, pollution control, petrochemical, and pharmaceutical syntheses. By considering every possible combination of the noble metals and oxide substrates, nine types of catalyst samples were produced. I characterized the structures of these catalysts, including their sizes, morphologies, crystallinity, and porosities, and their catalytic performances by using a representative reduction reaction from nitrobenzene to aminobenzene. Comparison of the catalytic results reveals the effects of the different noble metals, their incorporation amounts, and oxide substrates on the catalytic abilities. For this particular reaction, I found that Pd nanoparticles supported on mesoporous TiO₂ exhibit the best catalytic performance. The demonstrated low-cost and high-productivity preparation method can be extended to other catalysts, which can contain various metals and oxide substrates and will have high potential for industrial applications. Our preparation method also provides a platform for the studies of the synergetic catalytic effects between different oxide substrates and metals. / I further fabricated hollow mesoporous microspheres containing differently shaped noble metal nanocrystals. Hollow structures are strongly desired in many applications because of their high pore volumes, surface areas, and possible light-trapping effect. In my study, the hollow structures were obtained by simply dispersing polystyrene (PS) nanospheres into the precursor solution for aerosol spray. The PS spheres were removed by thermal calcination to produce hollow mesoporous microspheres. In my first study, the noble metal salts were dissolved in the precursor solutions, and the noble metal nanoparticles were obtained through thermal calcination. In this way, the size and shape of the metal nanoparticles cannot be well controlled. In my second study, I first grew noble metal nanocrystals and then incorporated them into the oxide supports. This preparation route allowed me to incorporate metal nanocrystals with controlled sizes, shapes, and compositions into the oxide matrices. The metal nanocrystals I used in this experiment included Pd nanocubes, Au nanorods, and Au corePd shell nanorods. These nanocrystals were functionalized with thiol-terminated methoxypoly(ethylene glycol) . The surface functionalization allowed them to adsorb on the PS spheres. After thermal calcination, the noble metal nanocrystals were left inside and adsorbed on the inner surface of the hollow mesoporous metal oxide microspheres. I investigated the catalytic activities of the Pd nanocube-embedded hollow mesoporous TiO₂ and ZrO₂ microspheres for the reduction of 4-nitrophenol to 4-aminophenol. I also examined the recyclability of the Pd nanocube-embedded hollow mesoporous ZrO₂ microsphere catalysts. The results showed that the combination of the noble metal nanocrystals and oxides prevents the aggregation of the nanostructures and reduces the loss of the catalysts during the recycling processes, leading to the remarkable recyclability of the hybrid catalyst. This method for the preparation of noble metal nanostructure-embedded hollow mesoporous oxide microspheres can greatly facilitate the investigation on the catalytic properties of noble metal nanocrystal and metal oxide hybrid nanostructures and therefore guide the design and fabrication of high-performance catalysts. / Last but not least, I investigated the magnetic mesoporous microspheres to enable a better recyclability of the mesoporous oxide catalysts. Both magnetic nanoparticle-included mesoporous metal oxides and mesoporous magnetic oxides were presented. The successfully syntheses of these microspheres will greatly improve the catalytic performance of the noble metal nanoparticle-loaded mesoporous oxide microspheres. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Jin, Zhao = 貴金屬納米顆粒負載的介孔金屬氧化物微納米球及其催化應用 / 金釗. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Jin, Zhao = Gui jin shu na mi ke li fu zai de jie kong jin shu yang hua wu wei na mi qiu ji qi cui hua ying yong / Jin Zhao. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgement --- p.v / Table of Contents --- p.vii / List of Figures --- p.x / List of Tables --- p.xvii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Mesoporous metal oxide materials --- p.1 / Chapter 1.1.1 --- Overview on mesoporous materials --- p.1 / Chapter 1.1.2 --- Syntheses of mesoporous metal oxides --- p.3 / Chapter 1.1.2.1 --- Preparation of mesoporous metal oxides through soft-templating methods --- p.3 / Chapter 1.1.2.2 --- Preparation of mesoporous metal oxides through hard-templating methods --- p.8 / Chapter 1.1.3 --- Applications of mesoporous metal oxides --- p.11 / Chapter 1.1.3.1 --- Catalysis --- p.12 / Chapter 1.1.3.2 --- Energy conversion and storage --- p.13 / Chapter 1.1.3.3 --- Sensing --- p.13 / Chapter 1.2 --- Noble metal nanopartilces --- p.15 / Chapter 1.2.1 --- Overview of noble metal nanoparticles --- p.15 / Chapter 1.2.2 --- Catalytic applications of noble metal nanoparticles --- p.19 / Chapter 1.2.2.1 --- Automotive converter --- p.19 / Chapter 1.2.2.2 --- Suzuki cross-coupling reaction --- p.20 / Chapter 1.3 --- The overview of this thesis --- p.22 / References --- p.24 / Chapter 2 --- Ultrasonic Aerosol Spray --- p.30 / Chapter 2.1 --- Working principle and our ultrasonic aerosol spray system --- p.30 / Chapter 2.2 --- Materials synthesized by the AASA method --- p.34 / References --- p.37 / Chapter 3 --- Materials Characterization Methods and Catalytic Studies --- p.39 / Chapter 3.1 --- Characterization methods --- p.39 / Chapter 3.2 --- Model catalytic reaction --- p.41 / References --- p.45 / Chapter 4 --- Noble Metal Nanoparticle-Loaded Mesoporous Oxide Microspheres --- p.46 / Chapter 4.1 --- Experiments --- p.48 / Chapter 4.2 --- Results and discussion --- p.50 / Chapter 4.2.1 --- Mesoporous metal oxide microspheres --- p.50 / Chapter 4.2.2 --- Noble metal nanoparticle-loaded mesoporous oxide microspheres --- p.55 / Chapter 4.3 --- Summary --- p.73 / References --- p.75 / Chapter 5 --- Metal Nanostructure-Embedded Hollow Mesoporous Oxide Microspheres Prepared with Polystyrene Nanospheres as Carriers and Templates --- p.78 / Chapter 5.1 --- Experiments --- p.83 / Chapter 5.2 --- Results and discussion --- p.88 / Chapter 5.2.1 --- Hollow mesoporous oxide microspheres prepared with the PS spheres as templates --- p.88 / Chapter 5.2.2 --- Noble metal nanostructure-embedded hollow mesoporous oxide microspheres --- p.90 / Chapter 5.3 --- Summary --- p.106 / References --- p.108 / Chapter 6 --- Magnetic Mesoporous Microspheres --- p.113 / Chapter 6.1 --- Experiment --- p.115 / Chapter 6.2 --- Results and discussion --- p.117 / Chapter 6.2.1 --- Magnetic nanoparticle-included mesoporous TiO₂ microspheres --- p.117 / Chapter 6.2.2 --- Mesoporous iron oxide microspheres --- p.125 / Chapter 6.3 --- Summary --- p.128 / References --- p.130 / Chapter 7 --- Conclusions --- p.131

No description available.

It has been demonstrated that 1,25 dihydroxy vitamin D3 (1,25 (OH)2VD3) can inhibit the proliferation of cancer cells including colorectal and hepatocellular cells which are mainly responsible for liver cancer. However, the use of 1, 25 (OH)2VD3 is hampered due to the development of hypercalcaemia. Current treatment using hepatic arterial delivery of drug solution is inconvenient since repetitive invasive treatments are required. This work aims to tackle this problem by utilizing crosslinked microspheres prepared by suspension polymerization as a carrier to control the release of 1, 25 (OH)2VD3 or hydrophobic drug in general at targeted sites over a long period. Poly(vinyl neodecanoate crosslinked ethyleneglycol dimethacrylate) microspheres in the size range of 35 m were prepared via suspension polymerization. Different parameters in suspension polymerization such as temperature, concentration and crosslinker percentage were studied in details. The effect of stabilizer on the formation of spheres was carefully investigated by using RAFT polymerization to produce various structures of the stabilizer, poly (vinyl pyrrolidone). Core- shell microspheres were also produced to enhance the hydrophilicity of the surface of microspheres. Hydrophobic drugs were loaded to these microspheres after reaction by the evaporation method. These microspheres were then used for drug loading and drug release study. Release study has shown that up to 10% of drug was released after 40 days. Cytotoxicity test reveals the suitability of this polymer for application in biomedical field. The MTT assay of Clofazimine loaded microspheres on the colorectal cancer cell lines HT29 has shown that the cell number was decreased about 50% after drug treatment.

It has been demonstrated that 1,25 dihydroxy vitamin D3 (1,25 (OH)2VD3) can inhibit the proliferation of cancer cells including colorectal and hepatocellular cells which are mainly responsible for liver cancer. However, the use of 1, 25 (OH)2VD3 is hampered due to the development of hypercalcaemia. Current treatment using hepatic arterial delivery of drug solution is inconvenient since repetitive invasive treatments are required. This work aims to tackle this problem by utilizing crosslinked microspheres prepared by suspension polymerization as a carrier to control the release of 1, 25 (OH)2VD3 or hydrophobic drug in general at targeted sites over a long period. Poly(vinyl neodecanoate crosslinked ethyleneglycol dimethacrylate) microspheres in the size range of 35 m were prepared via suspension polymerization. Different parameters in suspension polymerization such as temperature, concentration and crosslinker percentage were studied in details. The effect of stabilizer on the formation of spheres was carefully investigated by using RAFT polymerization to produce various structures of the stabilizer, poly (vinyl pyrrolidone). Core- shell microspheres were also produced to enhance the hydrophilicity of the surface of microspheres. Hydrophobic drugs were loaded to these microspheres after reaction by the evaporation method. These microspheres were then used for drug loading and drug release study. Release study has shown that up to 10% of drug was released after 40 days. Cytotoxicity test reveals the suitability of this polymer for application in biomedical field. The MTT assay of Clofazimine loaded microspheres on the colorectal cancer cell lines HT29 has shown that the cell number was decreased about 50% after drug treatment.

Thesis (Ph.D.)--University of Delaware, 2008. / Principal faculty advisor: Yan Jin, Dept. of Plant & Soil Sciences. Includes bibliographical references.

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

No description available.

Ultrasound irradiation of a protein or polymer solution at the air:water interface can be used to form hollow microspheres containing an air bubble. By introducing a layer of oil and sonicating the oil:water interface, microspheres containing an oil droplet are formed. The microspheres are stabilised by disulfide crosslinking, have diameters of between 1-20 mm and have a number of applications; gas filled protein microspheres are used as ultrasound contrast agents and oil filled microspheres are being developed for delivery of lipophilic drugs. This project extends the scope of sonochemically produced microspheres to include water-in-oil emulsion filled microspheres, which facilitate encapsulation of hydrophilic species, and polymer microspheres that release their contents in response to an external stimulus. Successful encapsulation of a water in oil emulsion phase is demonstrated using confocal microscopy. Release studies are reported for a number of hydrophilic species (in vitro) including 5,6-carboxyfluorescein, 5-fluorouracil and sodium chloride. Release can be triggered by sonochemical disruption of the microsphere shells or cleavage of the disulfide cross links. Thiol-ene coupling reactions initiated by ultrasound irradiation are reported. In water, ultrasound initiation of thiol-ene reactions with electron rich alkenes results in rates of reaction which compare favourably with conventional thermal initiation. Thiol-ene crosslinking is proposed as an alternative to disulfide crosslinking to stabilise sonochemically produced microspheres. Temperature responsive microspheres are produced via the sonochemical method using a block copolymer of N-isopropylacrylamide and thiolated methacrylic acid, P(MASH-b-NIPAm). The block co-polymer is synthesised using reversible addition-fragmentation transfer (RAFT) polymerisation and has a lower critical solution temperature (LCST) of 37 ºC. The microspheres formed from this block copolymer can be seen to rupture, releasing their internal oil phase, when heated above 37 ºC. These findings provide a basis from which to develop sonochemically produced polymer microspheres for responsive delivery of both hydrophilic and lipophilic species.

Thermally expandable microspheres are polymeric core/shell particles in which a volatile hydrocarbon is encapsulated by a thermoplastic shell. When these microspheres are heated, they expand and increase their volume dramatically. This volume increase is retained upon cooling, leading to a density reduction from around 1100 kg m-3 to about 30 kg m-3. Since the development in the early 1970´s, microspheres have been used extensively by the industry as a foaming agent or light weight filler. In this thesis, microspheres with a poly(acrylonitrile-co-methacrylonitrile) shell have been synthesized through free radical suspension polymerization. The microspheres have been characterized with respect to particle morphology and expansion properties in order to deepen the understanding of the microspheres. It was found that the monomer feed ratio and the polymerization temperature are very important parameters with respect to the expansion properties. Excellent expansion could only be accomplished when polymerizing at 62 °C, with the acrylonitrile feed, fAN, being around 60 mol%, even though core/shell microspheres are formed over a much wider range of fAN. Furthermore, no expansion was achieved when polymerizing at 80 °C, even though no noticeable differences were found, compared to the corresponding sample polymerized at 62 °C. It was also shown that the expansion properties can be modified by replacing the encapsulated hydrocarbon by another hydrocarbon with a different boiling point. Not only is the boiling point important, the structure of the hydrocarbon is also important. Isooctane which is highly branched was found to give superior expansion compared to linear or cyclic hydrocarbons having a similar boiling point. Crosslinking of the polymer shell has proven to be very important for the expansion properties. Both the amount and the structure of the crosslinker are important parameters. Especially the maximum expansion can be improved by the crosslinking of the polymer shell. This originates in an increase in the shape persistence of the expanded microspheres at elevated temperatures. By the combination of crosslinkers that are incorporated separately into the polymer shell, the onset temperature of expansion can be increased significantly. Finally, the surface of microspheres has been modified by grafting poly(glycidyl methacrylate) from the surface by ARGET ATRP. Given that the reaction conditions are appropriate, such modifications can be performed with only limited effects on the expansion properties of the microspheres.