Silver–titanium dioxide nanocomposites as effective antimicrobial and antibiofilm agents

Recent studies have revealed the existence of liver cancer stem cells (CSCs). Therefore, there is an urgent need for new and effective treatment strategies specific to liver CSCs. In this work, the poly(d,l-lactide-coglycolide) nanoparticles containing paclitaxel were prepared by emulsification-solvent evaporation method. The nanoparticles decorated with anti-CD133 antibody, termed targeted nanoparticles, were prepared by carbodiimide chemistry for liver CSCs. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, and in vitro release) were investigated. Cellular uptake and accumulation in tumor tissue of nanoparticles were observed. To assess anti-tumor activity of nanoparticles in vitro and in vivo, cell survival assay and tumor regression study were carried out using liver cancer cell lines (Huh7 and HepG2) and their xenografts. Particle size of targeted nanoparticles was 429.26 ± 41.53 nm with zeta potential of ?11.2 mV. Targeted nanoparticles possessed spherical morphology and high encapsulation efficiency (87.53 ± 5.9 %). The accumulation of targeted nanoparticles depends on dual effects of passive and active targeting. Drug-loaded nanoparticles showed cytotoxicity on the tumor cells in vitro and in vivo. Targeted nanoparticles resulted in significant improvement in therapeutic response through selectively eliminating CD133 positive subpopulation. These results suggested that the novel nanoparticles could be a promising candidate with excellent therapeutic efficacy for targeting liver CSCs.     

Facile Synthesis of Lactobionic Acid‐Targeted Iron Oxide Nanoparticles with Ultrahigh Relaxivity for Targeted MR Imaging of an Orthotopic Model of Human Hepatocellular Carcinoma

Development of multifunctional nanoprobes for tumor diagnosis is extremely important in the field of molecular imaging. In this study, the facile synthesis of lactobionic acid (LA)‐targeted superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) with ultrahigh relaxivity for targeted magnetic resonance (MR) imaging of an orthotopic hepatocellular carcinoma (HCC) is reported. Polyethyleneimine (PEI)‐stabilized Fe₃O₄ NPs prepared via a mild reduction route are sequentially coupled with fluorescein isothiocyanate and polyethylene glycol‐LA (LA‐PEG‐COOH) segment, followed by acetylation of the remaining PEI surface amines. The formed LA‐targeted Fe₃O₄ NPs are thoroughly characterized. It is shown that the developed multifunctional LA‐targeted Fe₃O₄ NPs are colloidally stable and water‐dispersible, display an ultrahigh r ₂ relaxivity (579.89 × 10^?3 m ^?1 s^?1) and excellent hemocompatibility and cytocompatibility in the given concentration range, and can target HepG2 cells overexpressing asialoglycoprotein receptors as confirmed by in vitro cellular uptake assay, flow cytometry, and confocal microscopy. Most strikingly, the developed multifunctional LA‐targeted Fe₃O₄ NPs can be used as a nanoprobe for targeted MR imaging of HepG2 cells in vitro and an orthotopic tumor model of HCC in vivo. With the ultrahigh r ₂ relaxivity and the versatile PEI amine‐mediated conjugation chemistry, a range of different Fe₃O₄ NP‐based nanoprobes may be developed for theranostics of different types of cancer.     

Monomer depletion, pressure difference, and membrane tube radius reduction due to fiber polymerization in microspikes

In many processes vital to life, the growth of biological fibers outwards from a membrane surface naturally produces membrane tube tethers or microspikes in biological cells. Here, we investigate the novel effect of pressure difference (due to monomer depletion) on the polymerization dynamics of biological fibers within long membrane tubes. We crucially find that fiber monomers become depleted close to the growing tip as the fiber polymerizes, thus reducing the local pressure, and hence decreasing the membrane tube radius at the tip. This process is found to slow the growth of the fiber, a process which becomes important when we go on to construct a dynamical theory for biopolymer growth in long, narrow tubes. Our result is interesting in that it emphasizes how "passive" biological transport mechanisms such as via pressure differences may play an important role in cell movements.     

Tumor shapes effect on metastatic state: A theoretical derivation embedding thermodynamic laws

Breaching away cells from an original primary tumor site and spreading throughout the body is hallmark definition of metastasis. To get the bottom line of this phenomenon, mathematical and thermodynamically based techniques have been developed and are being increasingly applied to help, decipher and forecast tumor pattern disturbing and treatment response. Becoming a primary tumor to metastatic one, remains as hot topic in many studies. In this study, an extensive complicated mathematical model was used and by embedding thermodynamic laws, three primary oversimplifying hypothetical tumors’ shape e.g. cylindrical, spherical, ellipsoidal were theoretically studied. After extracting within tumor flux pressures, we tried to compare aforementioned tumor shapes in terms of becoming a metastatic one e.g. cell rupturing. Our results shown it was not explicitly possible to address which tumor shapes shall get metastatic state (tear down in much earlier time than other shapes), as it was heavily dependent on tumor parameter values. The results of this study could be fairy appealing for both cancer model developer experts, medicines and cancer systems biologist as well.     

Targeted therapy of hepatocellular carcinoma with aptamer-functionalized biodegradable nanoparticles

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, occurring primarily in regions where viral hepatitis infections are common. Unfortunately, most HCC cases remain undiagnosed until late stages of the disease when patient outcome is poor, typically limiting survival from a few months to a year after initial diagnosis. In order to better care for HCC patients, new target-specific approaches are needed to improve early detection and therapeutic intervention. In this work, polymeric nanoparticles functionalized with a HCC-specific aptamer were examined as potential targeted drug delivery vehicles. Specifically, doxorubicin-loaded nanoparticles were prepared via nanoprecipitation of blends of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol). These particles were further functionalized with the HCC-specific TLS11a aptamer. The in vitro interaction and therapeutic efficacy of the aptamer and aptamer-functionalized nanoparticles were characterized in a hepatoma cell line. Nanoparticles were found to be spherical in shape, roughly 100–125 nm in diameter, with a low polydispersity (≤0.2) and slightly negative surface potential. Doxorubicin was encapsulated within the particles at ~40 % efficiency. Drug release was found to occur through anomalous transport influenced by diffusion and polymer relaxation, releasing ~50 % doxorubicin in the first 10 h and full release occurring within 36 h. Confocal microscopy confirmed binding and attachment of aptamer-targeted nanoparticles to the cell surface of cultured HCC cells. Efficacy studies demonstrated a significant improvement in doxorubicin delivery and cell-killing capacity using the aptamer-functionalized, drug-loaded nanoparticles versus controls further supporting use of aptamer nanoparticles as a targeted drug delivery system for HCC tumors.

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Graphical abstract In this work, polymeric nanoparticles functionalized with a liver cancer-specific aptamer were examined as potential targeted drug delivery vehicles. The aptamer-functionalized nanoparticles were found to significantly improve doxorubicin drug delivery and cell-killing capacity in vitro versus non-targeted controls, supporting their use as a targeted treatment toward liver cancer tumors.

     

钨系纳米颗粒与HepG2肿瘤细胞作用的瞬态吸收谱研究

利用MTT法研究了钨系纳米颗粒对HepG2肝肿瘤细胞抑制作用,利用瞬态吸收谱(TAS)技术的吸收发射谱表征肿瘤细胞和纳米粒子之间的电荷传递,讨论了钨系纳米颗粒在肿瘤疾病早期检测以及抗肿瘤特性。设计HepG2实验体系中,抗肿瘤活性的最佳药物浓度为100～150 μg·mL-1,反应时间在6 h之内很强,在24 h之内已经基本完成。实验证实,瞬态吸收谱技术可以作为肿瘤的检测方法,及表征纳米生物传感器和肿瘤细胞之间的电荷传递,钨系纳米颗粒具有作为抗肿瘤药物的应用前景。     

Contrast-enhanced dynamic MRI protocol with improved spatial and time resolution for in vivo microimaging of the mouse with a 1.5-T body scanner and a superconducting surface coil

Magnetic resonance imaging (MRI) is well suited for small animal model investigations to study various human pathologies. However, the assessment of microscopic information requires a high-spatial resolution (HSR) leading to a critical problem of signal-to-noise ratio limitations in standard whole-body imager. As contrast mechanisms are field dependent, working at high field do not allow to derive MRI criteria that may apply to clinical settings done in standard whole-body systems. In this work, a contrast-enhanced dynamic MRI protocol with improved spatial and time resolution was used to perform in vivo tumor model imaging on the mouse at 1.5 T. The needed sensitivity is provided by the use of a 12-mm superconducting surface coil operating at 77 K. High quality in vivo images were obtained and revealed well-defined internal structures of the tumor. A 3-D HSR sequence with voxels of 59x59x300 microm3 encoded within 6.9 min and a 2-D sequence with subsecond acquisition time and isotropic in-plane resolution of 234 microm were used to analyze the contrast enhancement kinetics in tumoral structures at long and short time scales. This work is a first step to better characterize and differentiate the dynamic behavior of tumoral heterogeneities.     

Development of a Liver‐Targeting Gold–PEG–Galactose Nanoparticle Platform and a Structure–Function Study

For the specific liver parenchymal cell delivery, a series of short heterobifunctional poly(ethylene glycol) (PEG) derivatives containing dimercapto and galactose (Gal) terminals is synthesized for the preparation of gold conjugates. The Gal density on the surface of all gold conjugates can be well controlled and the prepared gold conjugates are stable in various media, even in the presence of serum. For the liver targeting and reflectance imaging applications, the structure–function relationships of this platform, including the influence of the PEG molecular weight and the Gal ligand coverage of hybrid particles on the cytotoxicity and cellular recognition of tumor cells in vitro and on their liver‐targeting ability in small animals, are studied. Biocompatibility results show that HepG2 cells are more sensitive than HeLa cells to gold conjugates. Cellular uptake studies demonstrate that a lower PEG molecular weight, a higher Gal density, or a higher gold concentration can increase the cellular uptake efficiency of these hybrid particles in HepG2 cells when the other parameters are constant. The results reveal the importance of parameter modulation for the design and control of nanoprobes and the gold conjugates with short PEG chains and a high Gal density are a potential vector for active‐targeting therapy.     

Assessment of liver phagocytic activity using EPR spectrometry and imaging

The aim of the present study was to evaluate the usefulness of electron paramagnetic resonance (EPR) spectroscopy and imaging in assessing the phagocytic activity of the liver after administration of India ink. We conducted experiments on livers from control rodents and from rodents in which the Kupffer cell population had been depleted by pretreatment with gadolinium chloride. The EPR signal intensity recorded in liver homogenates was about two times lower in GdCl(3) treated rats than in control rats. EPR imaging carried out on precision-cut liver slices indicated a good correlation between the depletion of Kupffer cells and the EPR signal intensity.     

Is gadoxetic acid-enhanced MRI limited in tumor characterization for patients with chronic liver disease?

Purpose

There are pros and cons to the use of gadoxetic acid in hepatocellular carcinoma (HCC) workup due to the potential for high false positive diagnosis. This study was conducted to investigate the preoperative diagnostic performance of gadoxetic acid-enhanced MRI protocol including diffusion-weighted imaging (DWI) with emphasis on tumor characterization developed in high risk HCC patients.

Materials and methods

We included 144 patients (102 men, 42 women; age range 33–74 years) with chronic viral hepatitis or cirrhosis and 183 focal hepatic tumors (size range, 0.4–11.0 cm; mean, 3.2 cm), including 148 HCCs, 13 cholangiocarcinomas, 12 hemangiomas, three hepatocellular adenomas, two focal nodular hyperplasias, and five other tumors. All patients underwent gadoxetic acid-enhanced MRI protocol with DWI. MRIs were independently interpreted by three observers for the detection and characterization of hepatic tumors.

Results

Sensitivities for detecting all 183 liver tumors were 98.4%, 97.8%, and 96.2% for each observer, respectively, with a 97.5% for pooled data. Among 183 hepatic tumors, 91.3% (n = 167), 87.4% (n = 160), and 86.9% (n = 159) were correctly characterized according to their reference standard by each observer, respectively. In 13 cholangiocarcinomas, one to three were misinterpreted as HCC, and the remaining tumors were correctly characterized by each observer. The accuracies (Az) of MRI for HCC diagnosis were 0.952 for observer 1, 0.906 for observer 2, and 0.910 for observer 3, with 0.922 for pooled data. There was good inter-observer agreement.

Conclusion

The gadoxetic acid-enhanced MRI including DWI showed a reasonable performance for tumor characterization with high sensitivity for tumor detection in patients with chronic liver disease, despite concerns of high false positive diagnosis of hypervascular tumors.     

The Role of Surface Chemistry on Spreading Kinetics of Molten Silicides on Silicon Carbide

The spreading time for millimeter-sized droplets of nonreactive molten silicides on silicon carbide in high vacuum is several orders of magnitude higher than typical spreading times observed in nonreactive metal/ceramic systems. To explain this paradox, two types of experiments were performed: (i) wetting experiments for various nonreactive CuSi alloys on -SiC single crystals using the sessile drop and dispensed drop techniques, with emphasis on determining the initial contact angle; and (ii) characterization of surface chemistry of SiC after different heat treatments in high-vacuum furnaces. It is shown that spreading kinetics in these systems are controlled by the kinetics of removing of wetting barriers present or developed in situ on SiC surface.     

Cytotoxic effects and in vitro reversal of multidrug resistance by therapeutic ultrasound in human hepatocarcinoma cell line (HepG2)

Multidrug resistance (MDR) is one of the major obstacles to successful chemotherapy of human malignancies. Although many strategies have been explored to overcome MDR, none of them have been proven to be clinically useful until now. The aim of this study was to investigate whether a novel therapeutic ultrasound (US) approach would have useful effects on the reversal of MDR in cancer cells. Wild-type and MDR phenotype (HepG2/ADM) cells of the human hepatocarcinoma cell line HepG2 were exposed to 0.8 MHz US at an intensity of 0.43 W/cm² for a 9 s exposure (total energy density: 3.87 J/cm²). After US exposure, cell number and viability were counted immediately, and flow cytometry was performed to measure retention of rhodamine 123 and adriamycin in HepG2 and HepG2/MDR cells. Both cell lines were then incubated in suspension with adriamycin, vincristine, etoposide, cisplatin and 5-fluorouracil, respectively, and the MTT assay was used to determine cytotoxicity. The results showed that US exposure could significantly increase the uptake of Rh123 and ADM by HepG2/ADM tumor cells. The resistant index for the chemotherapeutic drugs was significantly lower in the US-exposed HepG2/ADM cells than in those not exposed to US. It was therefore concluded that US exposure could enhance the sensitivity of HepG2/ADM tumor cells to these chemotherapeutic agents, and the functional and structural changes induced by previous US exposure in MDR tumor cells may be responsible for it. However, further study is needed to investigate the mechanism behind US-mediated reversal of MDR.     

Platelet aggregation in the formation of tumor metastasis

Metastasis is the major cause of death from cancer, yet the optimal strategy against it remains uncertain. The pathogenesis of hematogenous metastasis is dynamic and consists of the following steps: 1) detachment of tumor cells from the primary site, 2) invasion into the host's blood vessels, 3) migration in the host's blood stream, 4) transport along the circulation, 5) arrest in or adhesion to the capillary in a distant organ, 6) extravasation, and 7) proliferation within the foreign tissues. A key to successful hematogenous metastasis is tumor survival in the bloodstream because most circulating tumor cells are rapidly destroyed by the shear forces or are attacked by the immune system. Less than 0.01% of these cells result in metastasis. Tumor cell-induced platelet aggregation has been reported to facilitate hematogenous metastasis by increasing the arrest of tumor cell emboli in the microcirculation. Platelet aggregation is also believed to protect tumor cells from immunological assault in the circulation. We have identified Aggrus as a platelet-aggregating factor expressed on a number of human cancers. Because hematogenous metastasis is reduced when neutralizing antibodies or eliminating carbohydrates attenuates Aggrus function, Aggrus's main contribution to hematogenous metastasis of Aggrus-expressing cells, then, is by promoting platelet aggregation. Aggrus could serve as an ideal target for drug development to block metastasis.     

Amphiphilic Core–Shell Nanocomposite Particles for Enhanced Magnetic Resonance Imaging

A scalable synthesis of magnetic core–shell nanocomposite particles, acting as a novel class of magnetic resonance (MR) contrast agents, has been developed. Each nanocomposite particle consists of a biocompatible chitosan shell and a poly(methyl methacrylate) (PMMA) core where multiple aggregated γ‐Fe₂O₃ nanoparticles are confined within the hydrophobic core. Properties of the nanocomposite particles including their chemical structure, particle size, size distribution, and morphology, as well as crystallinity of the magnetic nanoparticles and magnetic properties were systematically characterized. Their potential application as an MR contrast agent has been evaluated. Results show that the nanocomposite particles have good stability in biological media and very low cytotoxicity in both L929 mouse fibroblasts (normal cells) and HeLa cells (cervical cancer cells). They also exhibited excellent MR imaging performance with a T₂ relaxivity of up to 364 mM_Fe^?1 s^?1. An in vivo MR test performed on a naked mouse bearing breast tumor indicates that the nanocomposite particles can localize in both normal liver and tumor tissues. These results suggest that the magnetic core–shell nanocomposite particles are an efficient, inexpensive and safe T₂‐weighted MR contrast agent for both liver and tumor MR imaging in cancer therapy.     

CuBr激光充氢机理研究

详细研究了ＣｕＢｒ激光充氢后的激光动力学过程,解释了实验中观测到的两个现象：１）充氢后功率增大,其主要原因是：充氢使中心气体温度和ＣｕＢｒ分子蒸汽密度降低,从而减少了电子碰撞离解ＣｕＢｒ的有量损耗,导致电子温度上升。同时,脉冲期间的电子密度增加,电子密度的趋肤效应减弱,激光的“黑心”现象被改善。２）存在一个最佳充氢范围,其原因是：充氢后,随着气体温度的进一步降低,电子温度和铜原子度也将下降,它们与     

SOI部分耗尽SiGe HBT集电结空间电荷区模型

SOI上的薄膜异质SiGe晶体管通过采用"折叠"集电极,已成功实现SOI上CMOS与HBT的兼容.本文结合SOI薄膜上的纵向SiGe HBT结构模型,提出了包含纵向、横向欧姆电阻和耗尽电容的"部分耗尽 (partially depleted) 晶体管"集电区简化电路模型.基于器件物理及实际考虑,系统建立了外延集电层电场、电势、耗尽宽度模型,并根据该模型对不同器件结构参数进行分析.结果表明,空间电荷区表现为本征集电结耗尽与MOS电容耗尽,空间电荷区宽度随集电结掺杂浓度减小而增大,随集电结反偏电压提高而增大, 关键词： SOI SiGe HBT 集电区 空间电荷区模型     

光敏剂对肿瘤细胞损伤效应与孵育时间关系的拉曼光谱分析

利用拉曼光谱研究光敏剂与HepG2肝癌细胞不同孵育时间的光动力损伤效应。结果表明孵育时间与光动力损伤效应成正相关性,但孵育时间超过一定值,延长孵育时间并不能提高光动力损伤效应。     

肝脏肿瘤高分辨魔角旋转质子波谱分析

应用高分辨魔角旋转质子核磁共振波谱分析了正常肝脏（9例）、良性肿瘤（7例）及肝细胞癌（9例）代谢物变化. 半定量分析表明,肝细胞癌组织的甘氨酸、牛黄酸、胆碱、谷氨酸盐、丙氨酸、缬氨酸及乳酸明显高于正常对照和良性肝脏肿瘤组织. 实验结果表明肝细胞癌的代谢特征不同于正常肝脏和良性肝脏肿瘤. 不同肝脏组织的代谢改变可以通过高分辨魔角旋转质子核磁共振波谱检测.     

The use of T2*-weighted multi-echo GRE imaging as a novel method to diagnose hepatocellular carcinoma compared with gadolinium-enhanced MRI: a feasibility study

Background

The goal of the study was to assess a T2*-weighted MRI sequence for the ability to identify hepatocellular carcinoma (HCC).

Methods

Hepatic iron deposition, which is common in chronic liver disease (CLD), may increase the conspicuity of HCC on GRE imaging due to increased T2* signal decay in liver parenchyma. In this study, a breath-hold T2*-weighted MRI sequence was evaluated by a blinded observer for HCC and the results compared to a reference standard of gadolinium-enhanced MRI in these same patients. Forty-one patients (mean age 56.2 years; 17 females) were included in this approved, retrospective study.

Results

By the reference standard, 14 of 41 patients had a total of 25 HCCs. The sensitivity of the T2*-weighted MR sequence for identifying HCC, per lesion, was 60%, while the specificity was 100%. There was a significantly lower T2* value of liver parenchyma in patients with HCC identified by the T2*-weighted sequence than in those with HCCs which were not identified by the T2*-weighted sequence (27.8±2.2 vs. 21.9±2.1 ms; P=.02).

Conclusions

A T2*-weighted MRI sequence can identify HCC in patients with CLD. This technique may be beneficial for imaging of patients contraindicated for gadolinium.     

Thermal experiment of silicon PIN detector

The experiment of this paper is the thermal test of the leakage current of silicon PIN detector.Raising temperature may cause the detector to increase leakage current,decrease depletion and increase noise.Three samples are used in the experiment.One (called △E) is the sample of 100 tan in thickness.The other two (called E1 and E2) are stacks of five detectors of 1000 μm in thickness.All of them are 12 mm in diameter.The experiment has been done for 21 hours and with power on continuously.The samples have undergone more than 60 ℃ for about one hour.They are not degenerated when back to the room temperature.The depletion rate is temperature and bias voltage related.With the circuit of the experiment and temperature at 35 ℃,△E is still depleted while E1 and E2 are 94.9% and 99.7% depleted respectively.The noises of the samples can be derived from the values at room temperature and the thermal dependence of the leakage currents.With the addition of the noise of the pre-amplifier,the noises of E1,E2 and AE at 24 ℃ are 16.4,16.3,and 10.5 keV (FWHM) respectively while at 35 ℃ are about 33.6,33.1,and 20.6 keV (FWHM) respectively.