BACKGROUND & AIMS: :We tried to evaluate the possible involvement of fetuin in the scavenger receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size of 50 nm (NS-50), which has surface negative charge (zeta potential=-21.8+/-2.3 mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS-50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50 or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by cultured Kupffer cells was also significantly inhibited by poly I, and anti-class A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated the recognition and internalization of NS-50 by Kupffer cells and at least SR-A would be responsible for the uptake. Taken that Western blot analysis confirmed that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS-50 with serum, the results obtained in the present study indicate that fetuin would be one of the serum proteins that were substantially involved in the hepatic uptake of NS-50 via SRs.

背景与目标： : 我们试图评估胎球蛋白可能参与清道夫受体 (SRs) 介导的聚苯乙烯纳米球的肝摄取，其尺寸为50 nm (NS-50)，具有表面负电荷 (ζ 电位 =-21.8/-2.3 mV)。大鼠的肝脏灌注研究表明，预包被胎球蛋白 (NS-50-fetuin) 的NS-50的肝脏摄取被典型的SRs抑制剂聚肌苷酸 (poly I) 显着抑制，而普通NS-50或预包被的NS-50的肝脏摄取BSA (NS-50-BSA) 没有。培养的库普弗细胞对NS-50-fetuin的摄取也被poly I和抗A类清道夫受体 (sr-a) 抗体显着抑制，这表明NS-50上的胎球蛋白介导了库普弗细胞对NS-50的识别和内化，至少sr-a将负责摄取。认为Western印迹分析证实胎球蛋白在将NS-50与血清孵育后肯定吸附在NS-50表面，本研究获得的结果表明，胎球蛋白将是基本上参与肝脏摄取的血清蛋白之一NS-50通过SRs。

BACKGROUND & AIMS: :Among currently identified issues presenting risks and benefits to human and ocean health, engineered nanoparticles (ENP) represent a priority. Predictions of their economic and social impact appear extraordinary, but their release in the environment at an uncontrollable rate is in striking contrast with the extremely limited number of studies on environmental impact, especially on the marine environment. The sea urchin has a remarkable sensing environmental system whose function and diversity came into focus during the recent years, after sea urchin genome sequencing. The complex immune system may be the basis wherefore sea urchins can adapt to a dynamic environment and survive even in hazardous conditions both in the adult and in the embryonic life. This review is aimed at discussing the literature in nanotoxicological/ecotoxicological studies with a focus on stress and innate immune signaling in sea urchins. In addition, here we introduce our current development of in vitro-driven probes that could be used to dissect ENP aftermaths, suggesting their future use in immune-nanotoxicology.

背景与目标： : 在目前确定的对人类和海洋健康构成风险和益处的问题中，工程纳米颗粒 (ENP) 是优先事项。对它们的经济和社会影响的预测似乎非同寻常，但它们以无法控制的速度在环境中的释放与关于环境影响，特别是对海洋环境影响的研究数量极其有限形成鲜明对比。海胆具有出色的传感环境系统，其功能和多样性在近年来经过海胆基因组测序后成为人们关注的焦点。复杂的免疫系统可能是基础，因此海胆可以适应动态环境，即使在成年和胚胎生命的危险条件下也能生存。这篇综述旨在讨论纳米毒理学/生态毒理学研究中的文献，重点是海胆中的压力和先天免疫信号传导。此外，在这里，我们介绍了我们目前的体外驱动探针的开发，这些探针可用于解剖ENP后，暗示了它们在免疫纳米毒理学中的未来用途。

BACKGROUND & AIMS: :Annihilation of electrons-holes recombination process is the main remedy to enhance the photocatalytic activity of the semiconductors photocatalysts. Doping of this class of photocatalysts by foreign nanoparticles is usually utilized to create high Schottky barrier that facilitates electron capture. In the literature, because nonpolar nanoparticles (usually pristine metals, e.g., Ag, Pt, Au, etc.) were utilized in the doping process, the corresponding improvement was relatively low. In this study, CdSO4-doped TiO2 nanoparticles are introduced as a powerful and reusable photocatalyst for the photocatalytic degradation of methomyl pesticide in concentrated aqueous solutions. The utilized CdSO4 nanoparticles form polar grains in the TiO2 matrix due to the electrons leaving characteristic of the sulfate anion. The introduced nanoparticles could successfully eliminate the harmful pesticide under the sunlight radiation within a very short time (less than 1 h), with a removal capacity reaching 1,000 mg pesticide per gram of the introduced photocatalyst. Moreover, increase in the initial concentration of the methomyl did not affect the photocatalytic performance; typically 300, 500, 1,000, and 2,000 mg/l solutions were completely treated within 30, 30, 40, and 60 min, respectively, using 100 mg catalyst. Interestingly, the photocatalytic efficiency was not affected upon multiple use of the photocatalyst. Moreover, negative activation energy was obtained which reveals super activity of the introduced photocatalyst. The distinct photocatalytic activity indicates the complete annihilation of the electrons-holes recombination process and abundant existence of electrons on the catalyst surfaces due to strong electrons capturing the operation of the utilized polar CdSO4 nanoparticles. The introduced photocatalyst has been prepared using the sol-gel technique. Overall, the simplicity of the synthesizing procedure and the obtained featured photocatalytic activity strongly recommend the introduced nanoparticles to treat the methomyl-containing polluted water.

背景与目标： : 电子空穴复合过程的an灭是增强半导体光催化剂光催化活性的主要方法。通常利用外来纳米粒子对这类光催化剂进行掺杂，以产生促进电子捕获的高肖特基势垒。在文献中，由于在掺杂过程中使用了非极性纳米颗粒 (通常是原始金属，例如Ag、Pt、Au等)，因此相应的改进相对较低。在这项研究中，引入了CdSO4-doped TiO2纳米颗粒作为一种强大且可重复使用的光催化剂，用于在浓缩水溶液中光催化降解灭虫威农药。由于电子离开硫酸盐阴离子的特征，所利用的CdSO4纳米颗粒在TiO2基质中形成极性颗粒。引入的纳米颗粒可以在非常短的时间 (小于1小时) 内成功地消除太阳光辐射下的有害农药，去除能力达到每克引入的光催化剂1,000毫克农药。此外，灭虫威初始浓度的增加不影响光催化性能; 通常，使用100 mg催化剂分别在30、40和60分钟内完全处理300、500、1,000和2,000 mg/l溶液。有趣的是，多次使用光催化剂不会影响光催化效率。此外，获得了负活化能，这揭示了引入的光催化剂的超活性。独特的光催化活性表明电子-空穴复合过程完全an灭，并且由于强电子捕获了所利用的极性CdSO4纳米颗粒的操作，因此催化剂表面上电子的大量存在。引入的光催化剂是使用溶胶-凝胶技术制备的。总体而言，合成程序的简单性和所获得的特色光催化活性强烈建议引入的纳米颗粒来处理含灭多威的污染水。

BACKGROUND & AIMS: :Nanomedicine formulations such as biodegradable nanoparticles (nps) and liposomes offer several advantages over traditional routes of administration: due to their small size, nanocarriers are able to selectively accumulate inside tumours or inflammatory tissues, resulting in improved drug efficacy and reduced side effects. To further augment targeting ability of nanoparticles towards tumour cells, specific ligands or antibodies that selectively recognise biomarkers over-expressed on cancer cells, can be attached to the surface either by chemical bond or by hydrophilic/hydrophobic interactions. In the present work, Herceptin (HER), a monoclonal antibody (mAb) able to selectively recognise HER-2 over-expressing tumour cells (such as breast and ovarian cancer cells), was absorbed on the surface of nanoparticles through hydrophilic/hydrophobic interactions. Nps were prepared by a modified single emulsion solvent evaporation method with five different polymers: three commercial polyesters (poly(ε-caprolactone) (PCL), poly (D,L-lactide) (PLA) and poly (D,L-lactide-co-.glycolide) (PLGA)) and two novel biodegradable polyesterurethanes (PURs) based on Poly(ε-caprolactone) blocks, synthesised with different chain extenders (1,4-cyclohexane dimethanol (CDM) and N-Boc-serinol). Polyurethanes were introduced as matrix-forming materials for nanoparticles due to their high chemical versatility, which allows tailoring of the materials final properties by properly selecting the reagents. All nps exhibited a small size and negative surface charge, suitable for surface functionalisation with mAb through hydrophilic/hydrophobic interactions. The extent of cellular internalisation was tested on two different cell lines: MCF-7 and SK-BR-3 breast cancer cells showing a normal and a high expression of the HER-2 receptor, respectively. Paclitaxel, a model anti-neoplastic drug, was encapsulated inside all nps, and release profiles and cytotoxicity on SK-BR-3 cells were also assessed. Interestingly, PUR nps were superior to commercial polyester-based nps in terms of higher cellular internalisation and cytotoxic activity on the tested cell lines. Results obtained warrants further investigation on the application of these PUR nps for controlled drug delivery and targeting.

背景与目标： : 纳米药物制剂 (例如可生物降解的纳米颗粒 (nps) 和脂质体) 比传统的给药途径具有多个优势: 由于其体积小，纳米载体能够选择性地在肿瘤或炎症组织内积聚，从而提高药物功效并减少副作用。为了进一步增强纳米颗粒对肿瘤细胞的靶向能力，可以通过化学键或通过亲水/疏水相互作用将选择性识别在癌细胞上过度表达的生物标志物的特异性配体或抗体附着到表面。在目前的工作中，赫赛汀 (HER) 是一种能够选择性识别HER-2过表达肿瘤细胞 (如乳腺癌和卵巢癌细胞) 的单克隆抗体 (mAb)，通过亲水/疏水相互作用被吸收在纳米颗粒的表面上。用五种不同的聚合物通过改进的单乳液溶剂蒸发法制备了Nps: 三种商业聚酯 (聚 (ε-己内酯) (PCL)，聚 (D，L-丙交酯) (PLA) 和聚 (D，L-丙交酯-co-乙交酯 (PLGA)) 和两种基于聚 (ε-己内酯) 嵌段的新型可生物降解的聚酯氨基甲酸酯 (PURs)，用不同的扩链剂 (1,4-环己烷二甲醇 (CDM) 和N-Boc-丝氨酸) 合成。由于聚氨酯具有很高的化学通用性，因此被引入作为纳米颗粒的基质形成材料，这可以通过适当选择试剂来调整材料的最终性能。所有np均显示出小尺寸和负表面电荷，适合通过亲水/疏水相互作用与mAb进行表面官能化。在两种不同的细胞系上测试了细胞内在化的程度: 分别显示正常和高表达HER-2受体的MCF-7和SK-BR-3乳腺癌细胞。将紫杉醇 (一种模型抗肿瘤药物) 封装在所有np中，并评估其释放特性和对SK-BR-3细胞的细胞毒性。有趣的是，PUR nps在测试细胞系上具有更高的细胞内在化和细胞毒性活性方面优于商业基于聚酯的nps。获得的结果值得进一步研究这些PUR np在受控药物输送和靶向方面的应用。

BACKGROUND & AIMS: :With the increasing use of silver nanoparticles (Ag-NPs), their entrance into aquatic ecosystems is inevitable. Thus, the present study simulated the potential fate, toxicity, and bioaccumulation of Ag-NPs released into aquatic systems with different salinities. The Ag-NPs were characterized using inductively coupled plasma-atomic emission spectroscopy (ICP-AES), dynamic light scattering (DLS), transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), and UV-vis spectroscopy. Juvenile rainbow trout were exposed to Ag-NPs in three different salinity concentrations, including low (0.4 ppt), moderate (6 ± 0.3 ppt), and high (12 ± 0.2 ppt) salinity, for 14 days in static renewal systems. The nominal Ag-NP concentrations in the low salinity were 0.032, 0.1, 0.32, and 1 ppm, while the Ag-NP concentrations in the moderate and high salinity were 3.2, 10, 32, and 100 ppm. UV-vis spectroscopy was used during 48 h (re-dosing time) to evaluate the stability and possible changes in size of the Ag-NPs in the water. The results revealed that the λmax of the Ag-NPs remained stable (415-420 nm) at all concentrations in the low salinity with a reduction of absorbance between 380 and 550 nm. In contrast, the λmax quickly shifted to a longer wavelength and reduced absorbance in the moderate and higher salinity. The bioaccumulation of Ag in the studied tissues was concentration-dependent in all the salinities based on the following order: liver>kidneys≈gills>white muscles. All the tissue silver levels were significantly higher in the high salinity than in the moderate salinity. In addition, all the fish exposed to Ag-NPs in the low, moderate, and high salinity showed a concentration-dependent increase in their hepatosomatic index (HSI). In conclusion, most Ag-NPs that enter into freshwater ecosystems (low ionic strength) remain suspended, representing a potentially negative threat to the biota in an ionic or nanoscale form. However, in a higher salinity, nanoparticles agglomerate and precipitate on the surface of the sediment.

背景与目标： : 随着银纳米颗粒 (Ag-NPs) 的使用越来越多，它们不可避免地进入水生生态系统。因此，本研究模拟了释放到具有不同盐度的水生系统中的Ag-NPs的潜在命运，毒性和生物蓄积性。使用电感耦合等离子体原子发射光谱 (icp-aes)，动态光散射 (DLS)，透射电子显微镜 (TEM)，能量色散x射线分析 (EDX) 和紫外-可见光谱对Ag-NPs进行了表征。在静态更新系统中，将幼年虹鳟鱼暴露于三种不同盐度浓度的Ag-NPs中，包括低盐度 (0.4 ppt)，中度盐度 (6 ± 0.3 ppt) 和高盐度 (12 ± 0.2 ppt)，持续14天。低盐度下的标称Ag-NP浓度为0.032、0.1、0.32和1 ppm，而中高盐度下的Ag-NP浓度为3.2、10、32和100 ppm。在48小时 (重新给药时间) 内使用UV-vis光谱来评估水中Ag-NPs的稳定性和可能的大小变化。结果表明，在低盐度下，Ag-NPs的 λ max在所有浓度下均保持稳定 (415-420 nm)，吸光度降低在380至550 nm之间。相反，λ max在中等和较高盐度下迅速移至更长的波长，并降低了吸光度。根据以下顺序，在所有盐度中，Ag在研究组织中的生物积累均与浓度有关: 肝脏> 肾脏 ≈ g> 白色肌肉。在高盐度下，所有组织银含量均显着高于中盐度。此外，所有在低，中，高盐度下暴露于Ag-NPs的鱼的肝体指数 (HSI) 均呈浓度依赖性增加。总之，进入淡水生态系统 (低离子强度) 的大多数Ag-np仍然悬浮，代表着对离子或纳米级生物群的潜在负面威胁。但是，在较高的盐度下，纳米颗粒在沉积物表面聚集并沉淀。

BACKGROUND & AIMS: :As a homing peptide, A54 is the most effective peptide specific to the human hepatocellular carcinoma cell. Homing peptide labeled with green fluorescent protein (A54-GFP) was successfully immobilized on the surfaces of magnetic nanoparticles and characterized by Fourier transform infrared spectroscopy as well as fluorescence microscopy. The binding efficiency was analyzed by performing adsorption equilibrium and SDS-PAGE electrophoresis. Specific binding of the nanoparticles functionalized with A54-GFP to human hepatocellular carcinoma cells in vitro was visualized using fluorescence microscopy. The results demonstrated the specificity of A54-GFP-coated magnetic nanoparticle to tumor cell, pointing to its great potential in magnetic cell separation and purification, magnetic resonance imaging (MRI), magnetic hyperthermia, and drug targeting.

背景与目标： : 作为归巢肽，A54是对人肝癌细胞特异性最有效的肽。成功地将绿色荧光蛋白 (A54-GFP) 标记的归巢肽固定在磁性纳米颗粒的表面上，并通过傅里叶变换红外光谱和荧光显微镜对其进行了表征。通过进行吸附平衡和sds-page电泳分析结合效率。使用荧光显微镜观察用A54-GFP官能化的纳米颗粒在体外对人肝癌细胞的特异性结合。结果表明，A54-GFP-coated磁性纳米颗粒对肿瘤细胞具有特异性，表明其在磁性细胞分离和纯化，磁共振成像 (MRI)，磁热疗和药物靶向方面具有巨大潜力。

BACKGROUND & AIMS: :Cellulose from Musa balbisiana was purified. A part of it was dispersed in distilled water using ultrasonication. The silver nanoparticles (SNP) were synthesized in the colloidal cellulose solution and stability of the nanoparticles was tested using UV-Vis spectrophotometer. Further characterization of the composite was done using spectral analysis by Fourier Transform Infrared Spectroscopy (FTIR) to reveal any bond formation between silver nanoparticles with M. balbisiana cellulose. Here we found that cellulose/silver nanoparticle colloid is stable for 29 days and there is no chemical interaction of cellulose with silver nanoparticles.

背景与目标： : 纯化了来自Musa balbisiana的纤维素。使用超声将其一部分分散在蒸馏水中。在胶体纤维素溶液中合成了银纳米颗粒 (SNP)，并使用UV-Vis分光光度计测试了纳米颗粒的稳定性。使用傅立叶变换红外光谱 (FTIR) 的光谱分析对复合材料进行进一步表征，以揭示银纳米颗粒与M. balbisiana纤维素之间的任何键形成。在这里，我们发现纤维素/银纳米颗粒胶体在29天内稳定，并且纤维素与银纳米颗粒没有化学相互作用。

BACKGROUND & AIMS: :Nanomaterials hold great promise in the manipulation and treatments of mesenchymal stem cells, since they allow the modulation of their properties and differentiation. However, systematic studies have to be carried out in order to assess their potential toxicological effects. The present study reports on biocompatibility evaluation of glycol-chitosan coated barium titanate nanoparticles (BTNPs) on rat mesenchymal stem cells (MSCs). BTNPs are a class of ceramic systems which possess interesting features for biological applications thanks to their peculiar dielectric and piezoelectric properties. Viability was evaluated up to 5 days of incubation (concentrations in the range 0-100 μg/ml) both quantitatively and qualitatively with specific assays. Interactions cells/nanoparticles were further investigated with analysis of the cytoskeleton conformation, with SEM and TEM imaging, and with AFM analysis. Finally, differentiation in adipocytes and osteocytes was achieved in the presence of high doses of BTNPs, thus highlighting the safety of these nanostructures towards mesenchymal stem cells.

背景与目标： : 纳米材料在间充质干细胞的操作和治疗中具有广阔的前景，因为它们可以调节其特性和分化。但是，必须进行系统的研究以评估其潜在的毒理学作用。本研究报道了乙二醇-壳聚糖包被的钛酸钡纳米颗粒 (BTNPs) 对大鼠间充质干细胞 (MSCs) 的生物相容性评价。BTNPs是一类陶瓷系统，由于其独特的介电和压电特性，具有用于生物应用的有趣功能。通过特定测定定量和定性地评估孵育5天 (浓度在0-100 μ g/ml范围内) 的活力。通过分析细胞骨架构象，SEM和TEM成像以及AFM分析进一步研究了细胞/纳米颗粒的相互作用。最后，在高剂量BTNPs的存在下实现了脂肪细胞和骨细胞的分化，从而突出了这些纳米结构对间充质干细胞的安全性。

BACKGROUND & AIMS: :As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100 nm) TiO(2) nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO(2) nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO(2) nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO(2) nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms.

背景与目标： : 由于二氧化钛 (TiO(2)) 纳米颗粒在商业上被广泛使用，因此需要充分解释其潜在的生物安全性和代谢机理。在这项研究中，通过使用气相色谱仪分析小鼠成纤维细胞 (L929) 细胞及其相应培养基中代谢物谱的变化，研究了均质和弱聚集 (< 100  nm) TiO(2) 纳米颗粒的细胞毒性飞行时间质谱 (GC/TOFMS) 基于代谢组学策略。通过多元统计分析，在主成分分析 (PCA) 和正交偏最小二乘判别分析 (OPLS-DA) 模型中观察到令人满意的分离。基于OPLS-DA模型中的可变重要性，通过将TiO(2) 纳米颗粒处理的L929细胞或其相应的培养基与对照组进行比较，鉴定出一系列差异代谢物。发现在TiO(2) 纳米颗粒处理的L929细胞及其相应的培养基中，主要的生化代谢 (碳水化合物代谢) 受到抑制。这些结果可能解释了线粒体能量代谢的严重损害以及TiO(2) 纳米颗粒诱导的L929细胞中细胞氧化应激的增加。这些结果还表明，代谢组学策略在评估TiO(2) 纳米颗粒的细胞毒性方面具有巨大潜力，因此对理解其潜在的分子机制非常有帮助。

BACKGROUND & AIMS: :The synthesis and the characterization of three kinds of labeled silica nanoparticles were performed. Three different labeling strategies were investigated: fluorescent organic molecule (FITC) embedded in silica matrix, heavy metal core (Ag(0)) and radioactive core ((110m)Ag) surrounded by a silica shell. The main properties and the suitability of each kind of labeled nanoparticle in terms of size, surface properties, stability, detection limits, and cost were determined and compared regarding its use for transport studies. Fluorescent labeling was found the most convenient and the cheapest, but the best detection limits were reached with chemical (Ag(0)) and radio-labeled ((110m)Ag) nanoparticles, which also allowed nondestructive quantifications. This work showed that the choice of labeled nanoparticles as surrogates of natural colloids or manufactured nanoparticles strongly depends on the experimental conditions, especially the concentration and amount required, the composition of the effluent, and the timescale of the experiment.

背景与目标： : 进行了三种标记二氧化硅纳米颗粒的合成和表征。研究了三种不同的标记策略: 嵌入二氧化硅基质中的荧光有机分子 (FITC)，被二氧化硅壳包围的重金属核 (Ag(0)) 和放射性核 ((110m)Ag)。每种标记的纳米颗粒在尺寸方面的主要性质和适用性，确定了表面性质、稳定性、检测限和成本，并比较了其在运输研究中的用途。荧光标记被发现是最方便和最便宜的，但化学 (Ag(0)) 和放射性标记 ((110m)Ag) 纳米颗粒达到了最佳检测限，这也允许非破坏性定量。这项工作表明，选择标记的纳米颗粒作为天然胶体或制造的纳米颗粒的替代物在很大程度上取决于实验条件，尤其是所需的浓度和量，流出物的组成以及实验的时间尺度。

BACKGROUND & AIMS: :The limitations of anticancer drugs, including poor tumor targeting and weak uptake efficiency, are important factors affecting tumor therapy. According to characteristics of the tumor microenvironment, in this study, we aimed to synthesize matrix metalloproteinase (MMP)-responsive curcumin (Cur)-loaded nanoparticles (Cur-P-NPs) based on amphiphilic block copolymer (MePEG-peptide-PET-PCL) with MMP-cleavable peptide (GPLGIAGQ) and penetrating peptide (r9), modified to improve tumor targeting and cellular uptake. The average size of Cur-P-NPs was 176.9 nm, with a zeta potential of 8.1 mV, and they showed drug entrapment efficiency and a loading capacity of 87.07% ± 0.63% and 7.44% ± 0.16%, respectively. Furthermore, Cur release from Cur-P-NPs was sustained for 144 h at pH 7.4, and the release rate was accelerated under enzyme reaction condition. The MTT assay demonstrated that free P-NPs had favorable biosafety, and the anti-proliferative activity of Cur-P-NPs was positively correlated with Cur concentration in MCF-7 cells. Additionally, the results of cellular uptake, in vivo pharmacokinetics, and biodistribution showed that Cur-P-NPs had a good effect on cellular uptake and tumor targeting, resulting in the best bioavailability in tumor therapy. Therefore, Cur-P-NPs, as a promising drug delivery system, might lead to a new and efficient route for targeted therapy in clinical practice.

背景与目标： : 抗癌药物的局限性，包括肿瘤靶向性差和摄取效率弱，是影响肿瘤治疗的重要因素。根据肿瘤微环境的特点，在本研究中，我们的目标是基于两亲性嵌段共聚物 (MePEG-肽-PET-PCL) 与MMP可裂解肽 (GPLGIAGQ) 和穿透肽 (r9) 合成基质金属蛋白酶 (MMP) 响应姜黄素 (Cur) 负载的纳米颗粒 (Cur-P-NPs)，改进以提高肿瘤靶向和细胞摄取。Cur-P-NPs的平均尺寸为176.9  nm，zeta电位为8.1  mV，它们显示出药物包封效率和负载能力分别为87.07% ± 0.63% 和7.44% ± 0.16%。此外，在pH 7.4下，Cur-P-NPs的Cur释放持续144  h，并且在酶反应条件下释放速率加快。MTT分析表明，游离的P-NPs具有良好的生物安全性，并且Cur-P-NPs的抗增殖活性与MCF-7细胞中Cur浓度呈正相关。此外，细胞摄取，体内药代动力学和生物分布的结果表明，Cur-P-NPs对细胞摄取和肿瘤靶向具有良好的作用，从而在肿瘤治疗中获得最佳的生物利用度。因此，Cur-P-NPs作为一种有前途的给药系统，可能会为临床实践中的靶向治疗提供一条新的有效途径。

BACKGROUND & AIMS: :Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30-70 kDa with a presumably safer low molecular mass PVA 9-10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.

背景与目标： : 通过纳米颗粒向大脑输送药物是一种有前途的策略，可以为脑肿瘤的化学疗法开辟新的可能性。如先前的研究所证明的，在涂有泊洛沙姆188 (Dox-PLGA) 的聚 (丙交酯-共-乙交酯) 纳米颗粒中装载阿霉素使得这种细胞抑制素的脑递送正常不能以自由形式穿透血脑屏障。Dox-PLGA纳米颗粒对大鼠颅内101.8胶质母细胞瘤产生了非常显著的抗肿瘤作用，因此代表了值得临床评估的脑肿瘤化疗的有希望的候选者。因此，本研究的目的是优化Dox-PLGA配方和开发中试规模的制造工艺。制备程序的优化涉及技术参数的改变，例如用可能更安全的低分子量PVA 9-10 kda替换颗粒稳定剂PVA 30-70  kDa，以及外部乳液介质的改性和均质化条件。优化的程序能够将包封效率从66% 提高到> 90%，并将纳米颗粒尺寸从250纳米减小到110纳米，从而能够通过膜过滤进行灭菌。中试规模工艺的特点是具有极好的重现性，批次间变化非常小。在治疗相关浓度下，纳米颗粒的体外血液毒性可忽略不计。通过体内实验证实了优化配方的抗肿瘤功效以及纳米颗粒渗透到颅内肿瘤和正常脑组织中的能力。

BACKGROUND & AIMS: :Chitooligosaccharides are oligosaccharides with many biological activities that can be used in food production for sweeteners, preservatives and humectants, among other products. Chitin, a long-chain polymer of N-acetylglucosamine and a derivative of glucose, can be hydrolyzed by applying chitinase to break down glycosidic bonds to form chitooligosaccharides. Chitinases arising from heterologous gene expression are usually linked to a 6 × His-tag to facilitate easy purification. Heterologously expressed chitinase linked to a 6 × His-tag is a transgenic element, but enzyme activity tests cannot be used to distinguish transgenic elements from natural elements. In this study, we established a rapid and easy method to detect His-tag-containing chitinase using gold nanoparticles (AuNPs) and ssDNA aptamers. Using this method, His-tag-containing chitinase could be detected at concentrations as low as 0.136 nM within 5 min. Color changes of AuNPs showed a positive correlation with His-tag-containing chitinase concentrations.

背景与目标： : 壳寡糖是具有许多生物活性的寡糖，可用于食品生产中的甜味剂，防腐剂和保湿剂等产品。几丁质是N-乙酰氨基葡萄糖的长链聚合物和葡萄糖的衍生物，可以通过应用几丁质酶分解糖苷键以形成壳寡糖来水解。由异源基因表达产生的几丁质酶通常与6 × His标签连接，以方便纯化。与6 × His-tag连接的异源表达的几丁质酶是一种转基因元素，但是酶活性测试不能用于区分转基因元素与天然元素。在这项研究中，我们建立了一种快速简便的方法，使用金纳米颗粒 (AuNPs) 和ssDNA适体检测含His-tag的几丁质酶。使用该方法，可以在5分钟内以低至0.136 nM的浓度检测到含His-tag的几丁质酶。AuNPs的颜色变化与含His-tag的几丁质酶浓度呈正相关。

BACKGROUND & AIMS: :Aqueous suspension of magnetite nanoparticles with primary diameter of 10 nm were intratracheally administered into rat lungs. In 24 h, cells were isolated from bronchoalveolar lavage and examined under a transmission electron microscope. Alveolar macrophages demonstrated ability to actively uptake single nanoparticles and small aggregates composed of such particles, which then formed larger conglomerates inside fused phagosomes. Some of these mature phagosomes shed the membrane and free nanoparticles closely interacted with nuclear membrane and with cristae and mitochondrial membranes thereby inflicting pronounced damage to these intracellular structures. The loss of primary lysosomes can be viewed as indirect evidence attesting to the role played by diffusion of lysosomal hydrolytic enzymes in the final destruction of the alveolar macrophages provoked by nanoparticles.

背景与目标： : 将主直径为10 nm的磁铁矿纳米颗粒的水悬浮液气管内施用到大鼠肺中。在24小时内，从支气管肺泡灌洗中分离细胞，并在透射电子显微镜下检查。肺泡巨噬细胞表现出主动吸收单个纳米颗粒和由此类颗粒组成的小聚集体的能力，然后在融合的吞噬体内部形成更大的团聚体。这些成熟的吞噬体中的一些脱落了膜，游离的纳米颗粒与核膜以及cristae和线粒体膜紧密相互作用，从而对这些细胞内结构造成明显损害。初级溶酶体的丢失可以被视为间接证据，证明溶酶体水解酶的扩散在纳米颗粒引起的肺泡巨噬细胞的最终破坏中所起的作用。

BACKGROUND & AIMS: :Docetaxel (DTX), a widely prescribed anticancer agent, is now associated with increased instances of multidrug resistance. Also, being a problematic BCS class IV drug, it poses challenges for the formulators. Henceforth, it was envisioned to synthesize an analogue of DTX with a biocompatible lipid, i.e., palmitic acid. The in-silico studies (molecular docking and simulation) inferred lesser binding of docetaxel palmitate (DTX-PL) with P-gp vis-à-vis DTX and paclitaxel, indicating it to be a poor substrate for P-gp efflux. Solid lipid nanoparticles (SLNs) of the conjugate were prepared using various lipids, viz. palmitic acid, stearic acid, cetyl palmitate and glyceryl monostearate. The characterization studies for the nanocarrier were performed for the surface charge, drug payload, micromeritics, release pattern of drug and surface morphology. From the cytotoxicity assays on resistant MCF-7 cells, it was established that the new analogue offered substantially decreased IC50 to that of DTX. Further, apoptosis assay also corroborated the results obtained in IC50 determination wherein, SA-SLNs showed the highest apoptotic index than free DTX. The conjugate not only enhanced the solubility but also offered lower plasma protein binding and improved pharmacokinetic and pharmacodynamic effect for DTX loaded SA-SLNs in apt animal models, and lower affinity to P-gp efflux. The studies provide preliminary evidence and a ray of hope for a better candidate in its nano version for safer and effective cancer chemotherapy.

背景与目标： 多西紫杉醇 (DTX) 是一种广泛使用的抗癌药物，现在与多药耐药性增加有关。此外，作为一种有问题的BCS IV类药物，它给配方设计师带来了挑战。此后，设想合成具有生物相容性脂质 (即棕榈酸) 的DTX类似物。计算机研究 (分子对接和模拟) 推断多西紫杉醇棕榈酸酯 (dtx-pl) 与P-gp的结合相对于DTX和紫杉醇较小，表明它是P-gp外排的不良底物。使用各种脂质 (即棕榈酸，硬脂酸，棕榈酸十六烷基酯和单硬脂酸甘油酯) 制备缀合物的固体脂质纳米颗粒 (sln)。对纳米载体的表面电荷，药物有效载荷，微分生组织，药物的释放模式和表面形态进行了表征研究。根据对抗性MCF-7细胞的细胞毒性测定，可以确定新的类似物提供的IC50大大降低了DTX的IC50。此外，凋亡测定还证实了在IC50测定中获得的结果，其中sa-sln显示出比游离DTX最高的凋亡指数。该缀合物不仅增强了溶解度，而且还提供了较低的血浆蛋白结合，并改善了apt动物模型中DTX负载的sa-sln的药代动力学和药效学效果，并降低了对P-gp外排的亲和力。这些研究提供了初步的证据和一线希望，希望在其纳米版本中找到更安全，有效的癌症化学疗法。