Enhanced sonodynamic therapy by carbon dots-shelled microbubbles with focused ultrasound

Sonodynamic therapy involving the non-invasive and local generation of lethal reactive oxygen species (ROS) via ultrasound (US) with sonosensitizers has been proposed as an emerging tumor therapy strategy. However, such therapy is usually associated with inertial cavitation and unnecessary damage to healthy tissue because current sonosensitizers have insufficient sensitivity to US. Here, we report the use of a new proposed sonosensitizer, carbon dots (C-dots), to assemble microbubbles with a gas core (C-dots MBs). As the C-dots were directly integrated into the MB shell, they could effectively absorb the energy of inertial cavitation and transfer it to ROS. Our results revealed the appearance of ¹O₂, •OH, and H₂O₂ after US irradiation of C-dots MBs. In in vitro experiments, treatment with C-dots MBs plus US induced lipid peroxidation, elevation of intracellular ROS, and apoptosis in 32.5%, 45.3%, and 50.1% of cells respectively. In an animal solid tumor model, treatment with C-dots MBs plus US resulted in a 3-fold and 2.5-fold increase in the proportion of ROS-damaged cells and apoptotic cells, respectively, compared to C-dots MBs alone. These results will pave the way for the design of novel multifunctional sonosensitizers for SDT tumor therapy.     

Spectroscopic investigation on the sonodynamic activity of amsacrine (AMSA) to bovine serum albumin (BSA) damage

The sonodynamic damage of bovine serum albumin (BSA) under ultrasonic irradiation in the presence of amsacrine (AMSA) was studied by hyperchromic effect of UV-vis spectra and quenching effect of intrinsic fluorescence. In addition, several influencing factors such as ultrasonic irradiation time, AMSA concentration, system acidity and ionic strength about the damage of BSA molecules were reviewed. The results showed that the damage degree was obviously enhanced with the increase of ultrasonic irradiation time and AMSA concentration, but it was only slightly increased with the increase of solution pH value and ionic strength. Furthermore, the binding and damaging sites to BSA molecules were estimated by synchronous fluorescence spectra. The different chances to damage tryptophan (Trp) and tyrosine (Tyr) residues were found through the ratios of synchronous fluorescence quenching (R_SFQ). At last, the generation of reactive oxygen species (ROS) in sonodynamic process was estimated by the method of oxidation-extraction Spectrometry (OES). And then, several radical scavengers were used to determine the kind of ROS, which includes singlet oxygen (¹O₂) and hydroxyl radicals (·OH). Perhaps, the result would bring a certain guiding significance to use sonosensitive drugs in the fields of tumor treatment.     

Oxygen-carrying biomimetic nanoplatform for sonodynamic killing of bacteria and treatment of infection diseases

Among various novel antimicrobial therapies, sonodynamic therapy (SDT) exhibits its advantages for the treatment of bacterial infections due to its high penetration depth and low side effects. In this study, a new nanosonosensitizer (HFH@ZIF-8) that loads sonosensitizer hematoporphyrin monomethyl ether (HMME) into zeolitic imidazolate framework-8 (ZIF-8), was constructed for killing multidrug-resistant (MDR) bacteria and treatment of in vivo infection diseases by SDT. In particular, the developed HFH@ZIF-8 exhibited enhanced water-solubility, good biocompatibility, and improved disease-targeting capability for delivering and releasing HMME and ablating the infected lesion. More importantly, the presence of oxygen-carrying hemoglobin for HFH@ZIF-8 can offer sufficient oxygen consumption by SDT, augmenting the efficacy of SDT by improving ROS generating efficiency against deep tissue multidrug-resistant bacterial infection. Therefore, this study paves a new avenue for treating infection disease, particularly for antibiotic resistant bacterial infection.     

Surface modification of gold nanorods using layer-by-layer technique for cellular uptake

Gold nanorods (NRs), rod-shaped gold nanoparticles, were modified with bovine serum albumin (BSA) and polyethylenimine (PEI) using layer-by-layer technique. From absorption spectroscopy and zeta potential measurements, it was obvious that NRs were wrapped with these polymers without aggregation of NRs. Following BSA modification, the surface-modified NRs (BSA-NRs) were well-dispersed without aggregation in biochemical conditions, verified from absorption spectroscopy. Further modification with PEI provided positively charged NRs (PEI-NRs). A transmission electron microscopy image of PEI-NRs revealed that the surface modification did not affect changing the shape of the initial NRs. In addition, the PEI-NRs retained the colloidal stability of BSA-NRs in biochemical conditions. We have evaluated that transfection activity of PEI-NRs with HeLa cells. From results of gene expression experiments, it was obvious that the stabilization of NRs by BSA and further modification with PEI realized transfection using NRs into cultured cells. Moreover, the cellular uptake of NRs enabled cellular imaging using light scattering from the NRs.     

Seedless synthesis of gold nanorods by using hydrogen peroxide as a weak reducing agent

Abstract

A new seedless wet chemistry synthesis of gold nanorods by using hydrogen peroxide as the weak reducing agent is reported. A reduced concentration of hexadecyltrimethylammonium bromide is used in our experiment, and the synthesized gold nanorods exhibit tunable longitudinal surface plasmon resonance peaks ranging from 725 to 945?nm. The influence on gold nanorods growth by adjusting the amounts of sodium hydroxide, silver nitrate, sodium borohydride, and hexadecyltrimethylammonium bromide were investigated by the visible-near infrared spectroscopy. Under the proper experimental parameters, the longitudinal surface plasmon resonance peaks can be tuned by varying the hydrogen peroxide amounts. Furthermore, it can be seen that the redshift of the longitudinal absorption peak of the prepared gold nanorods with increasing hydrogen peroxide amount is consistent with the increase tendency of the length-to-width aspect ratio obtained from the transmission electron microscopy images. The method provides a facile pathway to prepare gold nanorods with tunable longitudinal surface plasmon resonance peaks, which have potential applications in biomedicine and nanophotonics.     

Oxygen and Indocyanine Green loaded microparticles for dual-mode imaging and sonodynamic treatment of cancer cells

Oxygen and Indocyanine Green (ICG) loaded microparticles (OI-MPs) were fabricated by a gas-driven coaxial flow focusing (CFF) process for dual-mode imaging and sonodynamic therapy (SDT). The produced OI-MPs agent showed stable optical properties, superior imaging depth in near infrared (NIR) fluorescence imaging, and enhanced acoustic contrast after ultrasound mediation. We hypothesized that encapsulating ICG and oxygen in microparticles would enhance reactive oxygen species (ROS) production in SDT. This hypothesis was validated in a cell-free environment. We further hypothesized that ultrasound mediated fragmentation of the OI-MPs would induce cytotoxicity and apoptosis of cancer cells. This hypothesis was validated in SKOV3 ovarian cancer cells. Our research demonstrated that OI-MPs can be potentially used as a dual-mode theranostic agent for image guided SDT with enhanced efficacy. Further study is needed to delineate the mechanism of ROS-induced cell apoptosis and optimize the OI-MPs formulation for the maximal anti-cancer potency.     

Synthesis of ZnO nanoparticles using surfactant free in-air and microwave method

Zinc oxide nanoparticles have been successfully prepared by a facile route involving the reaction of zinc sulphate heptahydrate and sodium hydroxide through drop-by-drop mixing synthesis-IA, instant mixing synthesis-IA and under the influence of microwave radiations. The synthesis under different reaction conditions played an important role and led to the formation of zinc oxide nanoparticles of different size and shapes. The synthesized nanoparticles were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. The concentration dependent antimicrobial activity of synthesized ZnO nanoparticles was carried out. The photocatalytic activity was evaluated using the photodegradation of methylene blue (MB) dye under UV irradiation. Further, the optical properties of as-prepared ZnO nanoparticles were investigated by UV-vis spectrophotometry. The absence of surfactant led to a simple, cheap and fast method of synthesis of zinc oxide nanoparticles.     

射流式单重态氧发生器研究

单重态氧O2 (a1Δg)是迄今唯一能用纯化学反应高效产生的具有长寿命的亚稳激发态分子 .为了考察提出的用两个O2 (1Δ)能量汇集反应生成氧第二单重激发态O2 (b1Σ+ g)以实现近可见短波长化学激光方案的现实性 ,设计和实验了一个氯流量为 3～ 10mmol/s的射流式单重态氧发生器 (JSOG) .考察了三种具有不同孔径和孔数目的喷头、氯气流量和脱水冷阱温度等对JSOG出口的O2 (1Δ)浓度、O2 (1Δ)分压、氯利用率及水蒸气含量的影响 .发现用聚氯乙烯管作冷阱时 ,最佳冷阱介质温度为 - 140～ - 15 0℃ ,对此提出了O2 (1Δ)表面脱活与脱水互相竞争的解释 .在最佳条件下 ,可将O2 (1Δ)气中水分压降低至 4Pa ,这一结果是首次报导     

Optimal design of gold nanoshells for optical imaging and photothermal therapy

Gold nanoshells are of great interest in optical imaging based on their light scattering properties and photothermal therapy due to their light absorption properties. Strong light scattering is essential for optical imaging, while effective photothermal therapy requires high light absorption. In this article, the optimal core radii and shell thicknesses of silica–gold and hollow gold nanoshells, possessing maximal light scattering and absorption at wavelengths between 700 and 1100 nm, are obtained using the Mie theory of a coated sphere. The results show that large-sized gold nanoshells of high aspect ratios (the aspect ratio is defined as the ratio of core radius to shell thickness) are the efficient contrast agents for optical imaging, while smaller gold nanoshells of high aspect ratios are the ideal therapeutic agents for photothermal therapy. From the comparison of the numerical results for silica–gold and hollow gold nanoshells, the latter are seen to offer a little superior light scattering and absorption at smaller particle size. Fitting expressions for the optimal core radii and shell thicknesses are also obtained, which can provide design guidelines for experimentalists to optimize the synthetic process of gold nanoshells.     

Sonication-assisted layer-by-layer deposition of gold nanoparticles for highly conductive gold patterns

Sonication-assisted layer-by-layer (LBL) deposition of gold nanoparticles (GNPs) was carried out in an attempt to prepare highly conductive gold patterns on polyimide substrates. First, sonication time was optimized with GNPs (12.8 nm) whose size was large enough to be analyzed by FE-SEM in order to evaluate the surface coverage. Next, multilayer formation (4, 8 and 12 layer) was confirmed using ethanedithiol (EDT) as linker molecules under optimized conditions by measuring their UV absorption, near-IR (NIR) transmittance, thickness, and electrical conductivity. Finally, 20-layer films using small GNPs (2.5 nm) were prepared with or without patterning, followed by sintering at 150 °C for 1 h, which provided clean gold patterns with high electrical conductivity (2.5 × 10⁵ Ω⁻¹ cm⁻¹).     

Laser therapy: A review of its mechanism of action and potential medical applications

Civilizations in antiquity have endeavored to champion the use of light to treat illnesses in the human body. Although laser light has unique applications in medicine, its mechanism of action for low intensity exposures on cells, tissues, and the body continues to be controversial after nearly 50 years of investigations. This paper presents evidence for visible red and near infrared light to induce (indirect) generation of hydrogen peroxide as an important chemical messenger behind the stimulatory and inhibitory responses observed to low intensity light exposures. It is hypothesized that other ionizing or non‐ionizing modalities can either directly or indirectly induce / or generate H₂O₂ in an aqueous environment and could also bring about similar stimulatory or inhibitory bio‐effects. One salient parameter which governs the bio‐response is the level of generated H₂O₂. The authors discuss the mechanism which enables a small amount of hydrogen peroxide generated by light to produce beneficial effects.     

荧光探针检测香烟主流烟雾活性氧的机理研究

不具有荧光的探针双氢罗丹明6G被氧化后可以生成具有荧光特性的罗丹明6G。反应中,一个双氢罗丹明分子能够与2个活性氧发生作用。借助衍生荧光检测技术,可以将该探针用于香烟主流烟雾活性氧含量的检测实验。利用探针在该实验条件下检测市场上4种品牌香烟的主流烟雾中活性氧的含量,含量分别为：(59.93±5.32)nmol,(55.98±6.17)nmol,(54.78±7.82)nmol,(40.87±6.43)nmol。实验结果表明,香烟主流烟雾中活性氧的含量与烟草品种及制作工艺存在密切的联系。借助荧光特性进行主流烟雾活性氧含量近实时检测的方法具有灵敏度高与检测速度快的特点。     

One injection for one-week controlled release: In vitro and in vivo assessment of ultrasound-triggered drug release from injectable thermoresponsive biocompatible hydrogels

Episodic release of bioactive compounds is often necessary for appropriate biological effects under specific physiological conditions. Here, we aimed to develop an injectable, biocompatible, and thermosensitive hydrogel system for ultrasound (US)-triggered drug release. An mPEG-PLGA-BOX block copolymer hydrogel was synthesized. The viscosity of 15 wt% hydrogel is 0.03 Pa*s at 25 °C (liquid form) and 34.37 Pa*s at 37 °C (gel form). Baseline and US-responsive in vitro release profile of a small molecule (doxorubicin) and that of a large molecule (FITC-dextran), from the hydrogel, was tested. A constant baseline release was observed in vitro for 7 d. When triggered by US (1 MHz, continuous, 0.4 W/cm²), the release rate increased by approximately 70 times. Without US, the release rate returned to baseline. Baseline and US-responsive in vivo release profile of doxorubicin was tested by subcutaneous injection in the back of mice and rats. Following injection into the subcutaneous layer, in vivo results also suggested that the hydrogels remained in situ and provided a steady release for at least 7 d; in the presence of the US-trigger, in vivo release from the hydrogel increased by approximately 10 times. Therefore, the mPEG-PLGA-BOX block copolymer hydrogel may serve as an injectable, biocompatible, and thermosensitive hydrogel system that is applicable for US-triggered drug release.     

医用质子加速器注入器7 MeV漂移管直线加速器的设计

针对质子治癌直线加速器功耗少、长度短的要求,设计了一台工作频率为324 MHz的漂移管型质子直线加速器(DTL)。该DTL把粒子从2.5 MeV加速到7 MeV,功耗为265 kW, 总长1.9 m。横向聚焦采用FODO结构,漂移管内放置永磁铁。提出一种新的束流匹配方案,在射频四极场加速器(RFQ)与DTL之间不设束运线,而是以 DTL入口处的4个单元为匹配段,把RFQ出口处相椭圆匹配到DTL周期结构入口处的相椭圆。 用PARMILA程序对该DTL进行了动力学模拟,结果表明该方案的束流发射度增长很小。     

Utilization of ultrasonic irradiation as a green and effective strategy to prepare poly(N-vinyl-2-pyrrolidone)/modified nano-copper (II) oxide nanocomposites

The present paper describes the result of investigations into preparation of novel nanocomposites (NCs) based on poly(N-vinyl-2-pyrrolidone) (PVP) as a biocompatible polymer and modified copper (II) oxide nanoparticles (NPs) as a nano-filler. To achieve optimum NCs properties, different ratios of modified copper (II) oxide NPs (3, 5, and 7 wt%) were used to fabricate PVP NCs and also the ultrasonic irradiation was utilized to perform these processes as a fast and effective method. Subsequently, the structure of the obtained nanohybrids was characterized by various techniques. The suitable incorporation between PVP matrix and modified CuO NPs can be seen from the FT-IR spectra. The obtained NCs indicated an efficient thermal improvement in comparison to the pristine polymer. Also, the uniform dispersion of modified CuO NPs in the PVP matrix was detected by FE-SEM and EDX. According to UV absorption spectra, it is clear that these NCs can be used in UV protecting applications.     

Local Au coverage as driving force for Au induced faceting of vicinal Si(0 0 1): a LEEM and XPEEM study

Adsorption of Au at 850°C on a regular stepped 4° vicinal Si(0 0 1) surface results in a dramatic change of the step morphology: the surface decomposes into areas which are perfectly flat with a (0 0 1) orientation and (1 1 9) facets. Low energy electron microscopy shows the dynamics of the faceting process in real space while X-ray photoemission electron microscopy (XPEEM) allows a spatially resolved determination of the Au coverage at different stages of the faceting process. At a critical Au coverage of ≈1/3 ML (0 0 1) terraces are formed which extend anisotropically along the step edges of the surface. The steps in between the terraces bunch and form step bands in order to conserve the macroscopic miscut of the sample. Driving force for this morphological transformation is a complex (5×3.2) reconstruction formed on the (0 0 1) terraces. XPEEM shows this phase separation also for the Au coverage: on the (0 0 1) terraces the Au coverage is up to 40% higher compared to the step bands. With further increasing Au coverage the width of the Au rich terraces increases while the step bands become steeper. In a second step Au adsorbs on the step bands transforming them into well defined and smooth (1 1 9) facets.     

新型原子电距矢量用于黄酮类化合物核磁共振碳谱的QSPR研究

改进原来的原子电性距离矢量,提出以6元素构建新的原子电性距离矢量,描述黄酮类化合物中不同等价碳原子的化学环境.对20个黄酮类化合物分子292个等价碳原子的13C-NMR化学位移建立了多元线性回归模型.该定量结构谱图关系(定量构谱关系/QSSR)模型的复相关系数达到RMM=0.9397,标准偏差为SDMM=7.6024 ppm.采用留一法交互检验的结果为RCV=0.9239,SDCV=8.5096 ppm.结果表明,模型具有良好的估计能力和稳定性.     

Comparison of Activated Carbon,Multiwalled Carbon Nanotubes,and Cadmium Hydroxide Nanowire Loaded on Activated Carbon as Adsorbents for Kinetic and Equilibrium Study of Removal of Safranine O

Activated carbon (AC), multiwalled carbon nanotube (MWCNT), and cadmium hydroxide nanowire loaded on activated carbon (Cd(OH)₂-NW-AC) have been used for the removal of safranine O (SO) from wastewater. The effects of various parameters including pH, temperature, concentration of the dye, amount of adsorbents, and contact time on the SO adsorption efficiency for all adsorbents has been investigated. Graphical correlation of fitting experimental data to various adsorption isotherm models like those of Langmuir, Freundlich, Tempkin, and Dubinin–Radushkevich for all adsorbents have been calculated. It was found that safranine O adsorption on all adsorbents was endothermic and feasible in nature. Fitting the experimental data to different kinetic models suggests that the adsorption process follows pseudo-second-order kinetics with involvement of the particle diffusion mechanism.     

An improved self‐assembly gold colloid film as surface‐enhanced Raman substrate for detection of trace‐level polycyclic aromatic hydrocarbons in aqueous solution

To detect trace‐level polycyclic aromatic hydrocarbons, some investigations of an improved self‐assembly method are carried out using gold colloid films for the preparation of the surface‐enhanced Raman scattering (SERS)‐active substrate. Extinction spectra and scanning electron microscopy images reveal that controllable surface plasmonic metal substrates can be obtained by increasing the temperature of (3‐aminopropyl)trimethoxysilane solution up to 64.5 °C. The SERS‐active substrates have a high enhancement factor, and they can be both easily prepared and reproducible. With the use of these substrates, different concentrations of pyrene and anthracene in aqueous solutions were detected by SERS. A further enhancement can be supported by shifted excitation Raman difference spectroscopy. Raman signals of pyrene and anthracene adsorbed on gold colloid substrates up to limits of detection at 5 and 1 nmol/l, respectively, can be obtained. The quantitative analysis shows the possibility of in situ detection of polycyclic aromatic hydrocarbons while such gold colloid film serves as a SERS‐active substrate. Copyright © 2012 John Wiley & Sons, Ltd.