Stimuli Responsive Nanoparticle for Cancer Targeted Therapy

Nanoparticle is the particle with a size in the range from several nanometers to hundreds of nanometers. It has been extensively used for cancer diagnosis and therapy. However, it is still a great challenge to fabricate nanoparticles with spatiotemporally controllable delivery of anticancer drugs to tumors and with high therapeutic efficacy. This thesis mainly focuses on the development of stimuli responsive nanoparticles for cancer targeted therapy. These nanoparticles either response to internal stimuli such as pH and redox potential or external stimuli like temperature and light could effectively target tumors and control the release of anticancer drugs there to improve their anticancer efficacy as well decrease adverse effects. We firstly developed a poly[(2-(pyridin-2-yldisulfanyl)ethyl acrylate)-co- [poly(ethylene glycol)]] (PDA-PEG) polymer and found that this polymer when combined with copper could efficiently kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. Next, we used this polymer or its derivatives to fabricate a series of stimuli responsive nanogels for targeted photodynamic therapy (PDT). These nanogels could efficiently target tumors under the help of targeting ligands and control photosensitizers release in the tumor by response to pH, redox potential and temperature, and finally induce high anticancer efficacy. To further improve the therapeutic efficacy, a polydopamine coated poly(lacticco- glycolic acid) nanoparticle was developed for chemo-thermal therapy. This nanoparticle could respond to near infrared light (NIR) to release the anticancer drug (doxorubicin) in the tumor and effectively eradicate head and neck tumor in a xenograft mouse model by combining the NIR-mediated photothermal therapy and doxorubicin induced chemotherapy

NF-kappa B mediated Up-regulation of CCCTC-binding factor in pediatric acute lymphoblastic leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequently occurring malignant neoplasm in children. Despite advances in treatment and outcomes for ALL patients, the pathogenesis of the disease remains unclear. Microarray analysis of samples from 100 Chinese children with ALL revealed the up-regulation of CTCF (CCCTC binding factor). CTCF is a highly conserved 11-zinc finger protein that is involved in many human cancers; however, the biological function of CTCF in pediatric ALL is unknown. METHODS: The expression patterns of CTCF were evaluated in matched newly diagnosed (ND), complete remission (CR), and relapsed (RE) bone marrow samples from 28 patients. The potential oncogenic mechanism of CTCF and related pathways in leukemogenesis were investigated in leukemia cell lines. RESULTS: We identified significant up-regulation of CTCF in the ND samples. Importantly, the expression of CTCF returned to normal levels after CR but rebounded in the RE samples. In the pre-B ALL cell line Nalm-6, siRNA-mediated silencing of CTCF expression promoted cell apoptosis and reduced cell proliferation; accordingly, over-expression of a cDNA encoding full-length CTCF protected cells from apoptosis and enhanced cell proliferation. Furthermore, inhibition or activation of the nuclear factor-kappa B (NF-κB) pathway resulted in marked variations in the levels of CTCF mRNA and protein in leukemic cells, indicating that CTCF may be involved downstream of the NF-κB pathway. Moreover, inhibition of the NF-κB pathway increased cell apoptosis, which was partially rescued by ectopic over-expression of CTCF, suggesting that CTCF may play a significant role in the anti-apoptotic pathway mediated by NF-κB. CONCLUSIONS: Our results indicate that CTCF serves as both an anti-apoptotic factor and a proliferative factor in leukemic cells. It potentially contributes to leukemogenesis through the NF-κB pathway in pediatric ALL patients

Advances of Microneedles in Biomedical Applications

A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different shapes (cone and pyramid) and forms (solid, drug-coated, hollow, dissolvable and hydrogel-based microneedles) have been developed. The main objective of this review is the applications of microneedles in biomedical areas. Firstly, the classifications and manufacturing of microneedle are briefly introduced so that we can learn the advantages and fabrications of different MNs. Secondly, research of microneedles in biomedical therapy such as drug delivery systems, diagnoses of disease, as well as wound repair and cancer therapy are overviewed. Finally, the safety and the vision of the future of MNs are discussed

A social commerce information propagation prediction model based on transformer

Precise forecasts of the propagation patterns of social commerce information play a crucial part in precision marketing. Traditional forecast relies on machine learning diffusion models, in which the forecast accuracy is dependent on the quality of the designed features. Researchers using these models are required to have experience in this regard, but due to the complexity and variations of real-world social commerce information propagation, design of features for the prediction model turns out difficult and is likely to cause local or universal errors in the model. To address these problems, this study proposed an information propagation prediction model based on Transformer. First, the fully-connected neural network was employed to code the user nodes to low-dimension vectors; then, Transformer was employed to perform information of the user-node vectors; last, the output of the Transformer was uploaded to the output layer to forecast the next user node in information propagation. The model was tested on data sets obtained from Sina Weibo, and the test result shows that the proposed model outperformed baseline models in terms of the indicators of Acc@k and MRR

ZrB2 powders with low oxygen content: Synthesis and characterization

A two-step reduction route is proposed for well-dispersed submicrometer ZrB2 powder synthesis with low oxygen content. The second synthesis step can reduce the oxygen content apparently, whereas presents minor adverse effects on particle size and dispersion of ZrB2 powders. The samples were mainly characterized by an oxygen-nitrogen analyzer and X-ray diffractometer (XRD). It can be determined that the adsorbed oxygen constitutes a low proportion of total oxygen content based on the release profile of oxygen and nitrogen contents. Besides, the oxygen content calculated based on XRD characterization is significantly lower than the total oxygen content measured by impulse-thermal conductivity. Furthermore, the lattice constants were determined according to XRD patterns as being higher than the calculated theoretical values based on the First-Principles, indicating that a portion of oxygen remains in ZrB2 powders in the form of interstitial impurity atoms.</p

Simulation and experimental observation of silicon particles' vaporization in RF thermal plasma reactor for preparing Si nano-powder

The particle size of coarse silicon is a very important parameter in plasma-assisted production of nano-silicon, because the appropriate size cannot only improve nano-silicon&#39;s quality, but also reduce the cost of raw materials. In this work, simulations were formulated to investigate the effect of particles&#39; size on silicon&#39;s vaporization process inside a radio-frequency (RF) thermal plasma reactor. By counting between particles&#39; residence time in a high temperature region and their fully-gasified time inside the reactor, particles&#39; motion and vaporization process can be obtained in statistics. After comparing these two parameters, the gasification ratio of coarse silicon with different sizes can be finally captured. It is shown that particles below 30 mu m all have the gasification ratio above 99.0%, which is suggested as the upper limit of coarse silicon in future experimental works. Moreover, it is also shown that gasification ratios of particles above 30 mu m are greatly reduced, illustrating that sacrificing gasification ratio to apply relatively bigger particles to prepare silicon nanopowder is inappropriate and uneconomical. (C) 2017 Elsevier B.V. All rights reserved.</p