39 research outputs found

    Machining of Aluminum Alloy

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    Import 23/07/2015Diplomová práce se zabývá kvalitou opracované hliníkové slitiny EN AW-6082, speciálně drsností povrchu a měřením a vyhodnocením složek řezných sil. Teoretická část objasňuje základní pojmy věnované čelnímu frézování, obrobitelnosti hliníku, obráběným materiálům, řezným podmínkám a geometrii obrábění. V návrhu experimentální části práce je popsáno použití stroje, nástroje a vyměnitelných břitových destiček, přístrojů na měření drsnosti, velikosti řezných sil a navržené řezné podmínky. V experimentální části práce jsou změřeny drsnosti povrchu a presentovány výsledky naměřených hodnot drsnosti Ra a Rz. Řezné síly byly měřeny na piezoelektrickém dynamometru.This master thesis is concerned with the quality of machined aluminium alloy EN AW-6082, especially surface roughness and the measurement and evaluation components of the cutting forces. The theoretical part explains the basic concepts of frontal milling, machinability aluminium, machined material, cutting conditions and geometry processing. In the proposal of the experimental part is described the using of machine, tool and indexable inserts, devices for measuring roughness, cutting forces and proposed cutting conditions. In the experimental part of the work are measured surface roughnesses and presented the results of the measured values of roughness Ra and Rz. Cutting forces were measured on the piezoelectric dynamometer.346 - Katedra obrábění, montáže a strojírenské metrologievelmi dobř

    Terrylenediimide-Based Intrinsic Theranostic Nanomedicines with High Photothermal Conversion Efficiency for Photoacoustic Imaging-Guided Cancer Therapy

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    Activatable theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, the theranostic nanomedicines widely suffer from instability and complicated nanostructures, which hamper potential clinical applications. Herein, we demonstrated a terrylenediimide (TDI)-poly­(acrylic acid) (TPA)-based nanomedicine (TNM) platform used as an intrinsic theranostic agent. As an exploratory paradigm in seeking biomedical applications, TDI was modified with poly­(acrylic acid)­s (PAAs), resulting in eight-armed, star-like TPAs composed of an outside hydrophilic PAA corona and an inner hydrophobic TDI core. TNMs were readily fabricated <i>via</i> spontaneous self-assembly. Without additional vehicle and cargo, the as-prepared TNMs possessed a robust nanostructure and high photothermal conversion efficiency up to approximately 41%. The intrinsic theranostic properties of TNMs for use in photoacoustic (PA) imaging by a multispectral optoacoustic tomography system and in mediating photoinduced tumor ablation were intensely explored. Our results suggested that the TNMs could be successfully exploited as intrinsic theranostic agents for PA imaging-guided efficient tumor PTT. Thus, these TNMs hold great potential for (pre)­clinical translational development

    Ultrasensitive Tyrosinase-Activated Turn-On Near-Infrared Fluorescent Probe with a Rationally Designed Urea Bond for Selective Imaging and Photodamage to Melanoma Cells

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    Melanoma is a highly aggressive malignancy and early monitoring and diagnosis are challenging at present. Tyrosinase is overexpressed in melanoma and regarded as an important biological marker for diagnosis and treatment. Thus, the selective and sensitive detection of tyrosinase is of great significance. To date, a few fluorescent probes have been reported for the detection of tyrosinase <i>in vitro</i> or <i>in vivo</i>. However, a highly sensitive near-infrared probe for tyrosinase monitoring is still missing. In this study, the Gibbs free energy change of different urea bonds during spontaneous hydrolysis is analyzed with the aid of chemical thermodynamic computation. On the basis of this analysis, we modified the dye methylene blue with a rationally designed urea bond to specifically create a probe, called MB1, for rapid detection of tyrosinase. Our experimental results demonstrated that MB1 can serve as a highly sensitive near-infrared responsive fluorescent probe for the monitoring and bioimaging of tyrosinase. In addition, the activated MB1 probe can effectively kill melanoma cells by photodynamic therapy. Thus, the near-infrared probe has great potential for monitoring and treating melanoma

    Multifunctional Metal Rattle-Type Nanocarriers for MRI-Guided Photothermal Cancer Therapy

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    In the past decade, numerous species of nanomaterials have been developed for biomedical application, especially cancer therapy. Realizing visualized therapy is highly promising now because of the potential of accurate, localized treatment. In this work, we first synthesized metal nanorattles (MNRs), which utilized porous gold shells to carry multiple MR imaging contrast agents, superparamagnetic iron oxide nanoparticles (SPIONs), inside. A fragile wormpore-like silica layer was manipulated to encapsulate 8 nm oleylamine SPIONs and mediate the <i>in situ</i> growth of porous gold shell, and it was finally etched by alkaline solution to obtain the rattle-type nanostructure. As shown in the results, this nanostructure with unique morphology could absorb near-infrared light, convert to heat to kill cells, and inhibit tumor growth. As a carrier for multiple SPIONs, it also revealed good function for <i>T</i><sub>2</sub>-weighted MR imaging in tumor site. Moreover, the rest of the inner space of the gold shell could also introduce potential ability as nanocarriers for other cargos such as chemotherapeutic drugs, which is still under investigation. This metal rattle-type nanocarrier may pave the way for novel platforms for cancer therapy in the future

    Sulfur-Doped NiFe Hydroxide Nanobowls with Wrinkling Patterns for Photothermal Cancer Therapy

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    Hierarchical multiscale wrinkling nanostructures have shown great promise for many biomedical applications, such as cancer diagnosis and therapy. However, synthesizing these materials with precise control remains challenging. Here, we report a sulfur doping strategy to synthesize sub-1 nm NiFe hydroxide ultrathin nanosheets (S-NiFe HUNs). The introduction of sulfur affects the reduction of the band gap and the adjustment of the electronic structure, thereby improving the light absorption ability of the S-NiFe HUNs. Additionally, S-NiFe HUNs show a multilayered nanobowl-like structure that enables multiple reflections of incident light inside the nanostructure, which improved the utilization of incident light and achieved high photothermal conversion. As a result, the as-prepared product with hydrophilic modification (dS-NiFe HUNs) demonstrated enhanced tumor-killing ability in vitro. In a mouse model of breast cancer, dS-NiFe HUNs combined with near-infrared light irradiation greatly inhibited tumor growth and prolonged the mice survival. Altogether, our study demonstrates the great potential of dS-NiFe HUNs for cancer photothermal therapy applications

    Synergistically Enhanced Therapeutic Effect of a Carrier-Free HCPT/DOX Nanodrug on Breast Cancer Cells through Improved Cellular Drug Accumulation

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    We are interested in developing systems for simultaneous delivery of two or more chemotherapeutic agents. Simple physical mixing of drugs may reduce the therapeutic effect and cause unexpected or even dangerous side-effects. For example, when 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) injection solutions are mixed, the curative effect is actually reduced in clinical practice. In this study we demonstrated that when HCPT and DOX are combined into a single nanoparticle, their toxicity to tumor cells <i>in vitro</i> is synergistically enhanced. We used a simple and “green” reprecipitation method to successfully create a carrier-free dual-drug delivery system by self-nanocrystallization of the drug molecules. When HCPT and DOX were coassembled, they formed small, spherical nanodrug particles with a positive surface charge. Cellular uptake of HCPT was improved and nuclear accumulation increased as much as 1.57-fold in comparison to HCPT alone. The carrier-free HCPT/DOX nanoparticles demonstrated enhanced synergistic cytotoxicity against breast cancer cells <i>in vitro</i>, while an antagonistic effect was observed when HCPT and DOX were directly mixed at high concentration

    Ultrasmall Gold Nanoparticles Behavior in Vivo Modulated by Surface Polyethylene Glycol (PEG) Grafting

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    Ultrasmall nanoparticles provide us with essential alternatives for designing more efficient nanocarriers for drug delivery. However, the fast clearance of ultrasmall nanoparticles limits their application to some extent. One of the most frequently used compound to slow the clearance of nanocarriers and nanodrugs is PEG, which is also approved by FDA. Nonetheless, few reports explored the effect of the PEGylation of ultrasmall nanoparticles on their behavior in vivo. Herein, we investigated the impact of different PEG grafting level of 2 nm core sized gold nanoparticles on their biological behavior in tumor-bearing mice. The results indicate that partial (∼50%) surface PEGylation could prolong the blood circulation and increase the tumor accumulation of ultrasmall nanoparticles to a maximum extent, which guide us to build more profitable small-sized nanocarriers for drug delivery

    Probe-Inspired Nano-Prodrug with Dual-Color Fluorogenic Property Reveals Spatiotemporal Drug Release in Living Cells

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    The versatility of the fluorescent probes inspires us to design fluorescently traceable prodrugs, which enables tracking the drug delivery kinetics in living cells. Herein, we constructed a self-indicating nanoprodrug with two fluorescent moieties, an aggregation-induced emission molecule (tetraphenylethylene, TPE) and a luminant anticancer drug (doxorubicin, DOX), with a pH-responsive linker between them. Except when a low pH environment is encountered, an energy-transfer relay (ETR) occurs and inactivates the fluorescence of both, showing a dark background. Otherwise, the ETR would be interrupted and evoke a dual-color fluorogenic process, giving distinct fluorogenic read out. By observing the dual-color fluorogenic scenario, we captured the kinetics of the drug release process in living cells. Because the separated TPE and DOX are both fluorescent but have a distinct spectrum, by examining the spatiotemporal pattern of TPE and DOX, we were able to precisely disclose the drug-releasing site, the releasing time, the destinations of the carriers, and the executing site of the drugs at subcellular level. Furthermore, different intracellular drug release kinetics between free doxorubicin and its nanoformulations were also observed in a real-time manner

    Zinc Oxide Nanoparticles as Adjuvant To Facilitate Doxorubicin Intracellular Accumulation and Visualize pH-Responsive Release for Overcoming Drug Resistance

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    Multidrug resistance (MDR) of cancer is a challenge to effective chemotherapeutic interventions. The stimulus-responsive drug delivery system (DDS) based on nanotechnology provides a promising approach to overcome MDR. Through the development of a doxorubicin delivery system based on zinc oxide nanomaterials, we have demonstrated that MDR in breast cancer cell line can be significantly circumvented by a combination of efficient cellular uptake and a pH-triggered rapid drug release due to degradation of nanocarriers in acidic environment. Doxorubicin and zinc oxide nanoparticles, compared with free doxorubicin, effectively enhanced the intracellular drug concentration by simultaneously increasing cell uptake and decreasing cell efflux in MDR cancer cells. The acidic environment-triggered release of drug can be tracked real-time by the doxorubicin fluorescence recovery from its quenched state. Therefore, with the combination of therapeutic potential and the capacity to track release of drug in cancer cells, our system holds great potential in nanomedicine by serving dual roles of overcoming drug resistance and tracking intracellular drug release from the DDS

    Gold Nanoparticles Induce Autophagosome Accumulation through Size-Dependent Nanoparticle Uptake and Lysosome Impairment

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    Development of nanotechnology calls for a comprehensive understanding of the impact of nanomaterials on biological systems. Autophagy is a lysosome-based degradative pathway which plays an essential role in maintaining cellular homeostasis. Previous studies have shown that nanoparticles from various sources can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. Gold nanoparticles (AuNPs) are one of the most widely used nanomaterials and have been reported to induce autophagosome accumulation. In this study, we found that AuNPs can be taken into cells through endocytosis in a size-dependent manner. The internalized AuNPs eventually accumulate in lysosomes and cause impairment of lysosome degradation capacity through alkalinization of lysosomal pH. Consistent with previous studies, we found that AuNP treatment can induce autophagosome accumulation and processing of LC3, an autophagosome marker protein. However, degradation of the autophagy substrate p62 is blocked in AuNP-treated cells, which indicates that autophagosome accumulation results from blockade of autophagy flux, rather than induction of autophagy. Our data clarify the mechanism by which AuNPs induce autophagosome accumulation and reveal the effect of AuNPs on lysosomes. This work is significant to nanoparticle research because it illustrates how nanoparticles can potentially interrupt the autophagic pathway and has important implications for biomedical applications of nanoparticles