Combination of doxorubicin with harmine-loaded liposomes exerting synergistic antitumor efficacy

Context: Long-circulation (PEGLip), pH-sensitive (PEOzLip), and active targeted liposomes (PEG-TATLip)-loading doxorubicin (DOX) and harmine (HM) were prepared. Their physicochemical properties and antitumor effect were investigated.

Objectives: The aims of the present study were to evaluate synergistic antitumor efficacy.

Materials and methods: Liposomes were prepared by using thin-film dispersion, active drug-loading and target post-insertion method. Subsequently physiochemical properties including particle size distribution, zeta potential, entrapment efficiency (EE), drug-loading content and in-vitro release were determined. Besides, the in vitro cytotoxicity of free drugs and drug-loaded liposomes was explored by using a Sulforhodamine-B Staining assay and the combination index values (CI Value) were calculated. Finally, the cellular uptake experiments by MCF-7cells were carried out via flow cytometry.

Results and discussion: All liposomes enhanced the antitumor effect significantly compared to free drugs. Among liposomes, PEG-TATLip enhanced the antitumor effect significantly compared to others. DOX and HM had moderate synergism with CI Value 0.85 for free drugs, 0.81 for PEGLip, 0.72 for PEOzLip, and 0.84 for PEG-TATLip respectively when the weight ratio of two drugs was 1:2. Moreover, the similarity between DOX and HM such as physicochemical properties, in vitro release modes and in vitro uptake kinetics characteristics when they were in the same formulations proved it possible for them to be delivered together.

Conclusion: Active targeting liposomes were the most effective delivery system as compared with pH-sensitive and long circulation liposomes. Additionally, DOX and HM could be co-delivered in liposomes and they could play moderate synergism effect in antitumor efficacy.     

A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver

Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin (BSA), was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo. This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strategy for tumor therapy.

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Preparation and antitumor activity of bFGF-mediated active targeting doxorubicin microbubbles

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE–PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 μm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.     

A novel hybrid combination optimization algorithm based on search area segmentation and fast Fourier transform

A novel hybrid optimization algorithm combining search area segmentation technique and the fast Fourier transform (HSAS/FFT) is presented to solve the numerical optimization problems. Firstly, the spectrum of each dimension of the objective function can be acquired by the FFT. The search space is segmented by using the spectrum to ensure that each subspace is unimodal. Secondly, the population of subspaces is produced and the optimal individual can be obtained by gradient descent algorithm. Finally, the local optimal solution in the optimal subspace is generated by the binary search algorithm. Make the optimal individual the new search space and repeat the process until meeting the termination condition. The proposed HSAS/FFT was tested on the CEC2017 benchmark, which evaluates the performance of the proposed algorithm on solving global optimization problems. Results obtained show that HSAS/FFT has an excellent performance and better convergence speed in comparison with some of the state-of-the-art algorithms.     

基于Tikhonov正则化及奇异值分解的载荷识别方法

针对矩阵求逆法应用中存在的病态逆问题,用Tikhonov正则化及奇异值分解法解决。通过对平板模型仿真分析,利用频响函数法矩阵条件数评价系统的病态性,系统病态性不同时用奇异值分解法与基于不同正则化参数选择的Tikhonov方法对载荷进行识别。研究表明,条件数大于1000时,Tikhonov正则化方法识别误差较小;反之,奇异值分解法较优。提出综合使用Tikhonov正则化与奇异值分解的载荷识别方法,给出方法流程。仿真与实验结果表明该方法可提高结构载荷识别精度,具有一定工程应用价值。     

基于无源伺服传感器的振动测量系统

针对工程领域（超）低频的振动问题,介绍了一种基于无源伺服传感器的振动测量系统。阐述了系统的特点和组成,着重分析了无源伺服反馈传感器的特点和原理,构建了传感器的数学模型,并比较了反馈前后传感器性能的差异,分析了反馈后传感器的基本参数。给出了部分测试数据和应用实例,分析了系统的抗干扰问题。最后,给出了一些结论。     

一种实现目标定位与跟踪的新方法

本文介绍了一种采用圆周阵对目标声源进行被动定位和跟踪的方法，与线阵不同，圆四可对目标进行全方位跟踪，且测距精度不受目标方位变化的影响，文中给出了圆周阵的测距，测向公式，并从理论上分析了测距性能，计算机仿真结果验证了理论分析的正确性。     

The in vivo effect of liposomes on hematopoiesis

The influence of liposome structure on hematopoiesis in vivo was assessed in relation to the different contents and origins of phospholipids that make up their membrane structures. Changes within different hematopoietic cells and serum tumor necrosis factor alpha (TNF-alpha) levels were estimated up to 14 days following intravenous administration of liposomes made of either pure egg yolk phosphatidylcholine (LEY) or a soybean phospholipid preparation (LSB) into normal CBA mice. In peripheral blood, only transient changes within white blood cells were observed. In bone marrow, a persistent decline in the number of mature granulocytes, monocytes, and lymphocytes was found. The changes within femoral granulocytic proliferative compartments in various stages of differentiation and a maturation compartment pointed out that, parallel with the depletion of the granulocyte-storage pool, stimulation of de novo production of granulocytic cells occurred. Although both types of tested liposomes induced similar cellular changes, only liposomes made of pure egg yolk phosphatidylcholine induced a transient increase in serum TNF-alpha levels.     

A novel honokiol liposome: formulation,pharmacokinetics, and antitumor studies

Abstract

It is necessary to discover a novel antitumor liposome with prolonged circulation time, high efficacy, and low cost. Here, we reported a liposomal honokiol (HNK) prepared with a new type of excipient, Kolliphor HS15, which was termed as HS15-LP-HNK. In addition, we employed PEGylated liposomal honokiol (PEG-LP-HNK) as positive control. The HS15-LP-HNK was prepared by thin-film hydration method. It was near-spherical morphology with an average size of 80.62?±?0.72?nm (PDI = 0.234?±?0.007) and a mean zeta potential of ?3.91?±?0.06?mv. In vivo studies exhibited no significant difference between HS15-LP-HNK and PEG-LP-HNK. The pharmacokinetic and biodistribution results showed that HS15-LP-HNK could improve the bioavailability and increase tumor accumulation of honokiol. Furthermore, HS15-LP-HNK could enhance antitumor efficacy of honokiol with low toxicity. In summary, HS15-LP-HNK is promising in tumor targeted drug delivery system.     

The effect of γ radiation on the electrical properties of passive coatings based on lead borosilicate glasses

The effect of irradiation with γ-quanta in a dose range from 10⁴ to 2×10⁷ rad on the electrical properties of passive coatings based on low-melting lead borosilicate glasses was studied. It is shown that the irradiation leads to accumulation of a positive charge in the volume of passive coatings. The radiation-induced charge exhibits saturation at an irradiation dose above 5×10⁶ rad.     

基于组合算法的金属铣削毛刺预测

利用最优权值系数,将灰色理论、人工神经网络和遗传算法有机结合,构建组合算法,依据3种数学方法建立3种组合模型：组合算术平均模型、组合平方和平均模型以及组合比例平均模型,并分别将3种组合模型应用于45钢铣削毛刺的预测．利用3个预测误差评价指标,即平方和误差指标、平均绝对误差指标和平均相对误差指标,对各模型的预测结果进行分析计算.结果表明,组合算术平均模型所得结果与实验结果取得了较好的吻合,具有较高的精度和稳定性,对于金属铣削毛刺的预测具有实际的应用价值．     

一种基于色彩处理的被动声呐宽带目标检测显示方法

针对被动声呐传统宽带能量检测方式难以解决强干扰存在时的弱目标检测问题,着眼于目标、干扰及背景噪声频谱特征差异,提出了一种划分子带,利用颜色合成理论进行宽带融合检测的显示方法。针对弱目标存在稳定线谱或在部分频点能量相对较强的情况,可有效提升对弱目标的检测能力,并增强不同目标方位历程的区分度。     

A novel urea biosensor based on zirconia

Electrochemically deposited biocompatible zirconia (ZrO₂) film on gold coated glass electrodes has been utilized for the fabrication of urea biosensor. The prepared ZrO₂ films and bioelectrodes have been characterized using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and electrochemical techniques, respectively. The urea biosensor, fabricated by immobilizing mixed enzyme [urease (Urs) and glutamate dehydrogenase (GLDH)] on this nanobiomaterial, shows linearity up to 40 mg dL^− 1 of analyte (urea) and sensitivity of 0.071 μA/(mM cm^− 2) with stability up to 4 months when stored at 4 °C. The low value of Michaelis-Menten constant (K_m) estimated using Hans plot as 0.5 mM indicates enhancement in the affinity and/or activity of enzyme attached to this nanostructured biocompatible matrix.     

基于可靠度和一致强度的冲突证据组合算法

考虑到利用无线传感器网络对天然气管道进行泄漏监控时,不同传感器节点的诊断结果之间会发生冲突,致使直接利用Dempster-Shafer (D-S)组合规则或其修正组合规则进行冲突证据组合的方法难以让汇聚节点做出正确决策,为此提出了一种基于可靠度和一致强度的冲突证据组合算法--CECARCI.该算法首先利用各监测节点的可靠度对证据集进行预处理,减小不可靠证据对组合结果的影响,然后通过对所有证据进行整体分析,引入了证据一致强度和基元支持度,调整证据组合时的次序,并以合理的权重来分配证据间的冲突.算例实验结果表明,相比于D-S组合法则、Yager组合法则和Murphy组合法则,CECARCI算法可获得收敛性更好的组合结果.     

A reconstituted thermosensitive hydrogel system based on paclitaxel-loaded amphiphilic copolymer nanoparticles and antitumor efficacy

Combination delivery systems composed of injectable hydrogels and drug-incorporated nanoparticles are urgently in regional cancer chemotherapy to facilitate efficient delivery of chemotherapeutic agents, enhance antitumor efficiency, and decrease side effects. Here, we developed a novel thermosensitive amphiphilic triblock copolymer consisting of methoxy poly(ethylene glycol), poly(octadecanedioic anhydride), and d,l-lactic acid oligomer (PEOALA), built a combination system of thermosensitive injectable hydrogel PTX/PEOALA^Gel based on paclitaxel (PTX)-loaded PEOALA nanoparticles (NPs). PTX/PEOALA^Gel could be stored as freeze-dried powders of paclitaxel-loaded PEOALA NPs, which could be easily redispersed into the water at ambient temperature, and form a hydrogel at the injected site in vivo. The in vitro cytotoxicity of PTX/PEOALA^Gel showed no obvious cytotoxicity in comparison with Taxol® against MCF-7 and HeLa cells. However, the in vivo antitumor activity showed that a single intratumoral injection of the PTX/PEOALA^Gel formulation was more effective than four intravenous (i.v.) injections of Taxol^® at a total dosage of 20?mg/kg in inhibiting the growth of MCF-7 tumor-bearing Balb/c mice, and the inhibition could be sustained for more than 17 d. The pharmacokinetic study demonstrated that the intratumoral injection of PTX/PEOALA^Gel could greatly decrease the systemic exposure of PTX, as confirmed by the rather low plasma concentration, and prolonged circulation time and enhanced tumor PTX accumulation, implying fewer off-target side effects. In summary, the PTX/PEOALA^Gel combination local delivery system could enhance tumor inhibition effect and tumor accumulation of PTX, and lower the systemic exposure. So, the reconstituted PTX/PEOALA^Gel system could potentially be a useful vehicle for regional cancer chemotherapy.     

提高被动声纳宽带检测性能的一种新方法

宽带能量检测是被动声纳实现目标探测功能的常用方法,常规能量检测(Conventional Energy Detection,CED)方法在复杂环境下的检测性能迅速降低.子带峰值能量检测(Subband Peak Energy Detection,SPED)可以有效改善常规能量检测方法的性能,提高时间方位历程显示(BTR...     

A novel ethanol gas sensor based on ZnO-microwire

One-dimensional (1D) ZnO microwires were successfully synthesized by chemical vapor deposition and their structural and morphological properties were analyzed by X-ray diffraction and scanning electron microscopy, demonstrating that the microwires were single crystalline with perfect hexagonal structure and smooth surface. Using these 1D microstructures, we fabricated a novel ZnO-based ethanol gas sensor. Operating at room temperature, the sensor was found to have good sensing characteristics. The reliability and stability of the sensor could be improved by connecting multiple 1-wire devices (1-WD) in parallel into a multi-wires device. In interior natural lighting environment and under 3 V bias, the response and recovery time of the 1-WD to 200 ppm ethanol gas were <10 s and about 300 s, respectively, and the minimum and maximum detection limit were about 2 and 200 ppm, respectively. A sensing model was proposed for discussing the performance of the sensor. The simplicity in fabrication, low power consumption and low cost make the sensor suitable for practical application in many fields, especially in identifying driving under the influence and chemical industry monitoring.     

一种基于模式识别的新型双端检测器

本文提出了一种基于最近邻线分类器的新的双端检测器（DTD）。主要的思想是充分地利用特征信息以及用模式识别方法来设计DTD。本文从模式分类的角度分析了二种主要的传统DTD（Geigel和相关DTD）并给出了新的设计方法。一种称为NNL分类器的新的非参数分类器被用来检测双端通话。NNL分类器具有低运算量和优良的性能。用NNL分类器．我们熔合了几种传统的DTD并且避免了存在于大多数传统DTD中的固定阈值带来的问题。因此NNL-DTD在各种条件下是鲁棒的。实验结果也显示出了这个方法比传统方法更有效。     

Targeted combination therapy for glioblastoma by co-delivery of doxorubicin,YAP-siRNA and gold nanorods

The combination of brain targeting drug delivery systems and multi-modal intervention pose a promising therapeutic approach for glioblastoma therapy.In this study,we developed an angiopep-2 peptide modified cationic liposome loaded with doxorubicin,YAP-siRNA and gold nanorods(D/R@Ang2-Lip+Au)simultaneously,which has high encapsulating efficiency for doxorubicin(95.4%)and effective binding of siRNA at N/P ratio of 20:1.The fluorescence imaging and flow cytometry analysis revealed high cellular uptake of D/R@Ang2-Lip+Au.Real-time quantitative polymerase chain reaction and western blot analysis indicated that D/R@Ang2-Lip+Au could effectively inhibit the expression of YAP protein.In vitro and in vivo studies showed that D/R@Ang2-Lip+Au had the ability to target glioblastoma cells,and achieved better anti-proliferative effects compared with non-targeted D/R@Lip+Au.Moreover,in vivo experiment demonstrated that D/R@Ang2-Lip+Au was able to cross the blood-brain barrier,and combination therapy could significantly inhibit tumor growth.Therefore,the multifunctional D/R@Ang2-Lip+Au might provide a novel approach for effectively delivery of DOX,YAP-siRNA and AuNRs into the glioblastoma cells simultaneously and exerting synergistic therapeutic effects.