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。

BACKGROUND & AIMS: :pH-Responsive nanoparticles composed of chitosan (CS) and poly-gamma-glutamic acid (gamma-PGA) blended with tripolyphosphate (TPP) and MgSO(4) (multi-ion-crosslinked NPs) were prepared and characterized to determine their effectiveness in the oral delivery of insulin. Their counterparts without TPP and MgSO(4) (NPs) were used as a control. FT-IR and XRD results indicated that the spontaneous interaction between CS, insulin, gamma-PGA, MgSO(4) and TPP can form an ionically crosslinked network-structure, leading to the formation of nanoparticles. Multi-ion-crosslinked NPs were more compact than NPs, while their zeta potential values were comparable. During storage, multi-ion-crosslinked NPs suspended in deionized water were stable for at least 10 weeks. Multi-ion-crosslinked NPs had a superior stability over a broader pH range than NPs. In the in vitro release study, NPs failed to provide an adequate retention of loaded insulin in dissolution media compared to multi-ion-crosslinked NPs. Transepithelial-electrical-resistance and transport experiments demonstrated that multi-ion-crosslinked NPs significantly more effectively transported insulin than NPs; confocal visualization further validated the enhanced permeation of insulin via the paracellular pathway. The aforementioned results suggest that multi-ion-crosslinked NPs are a promising carrier for improved transmucosal delivery of insulin in the small intestine.

背景与目标： : 制备了由壳聚糖 (CS) 和聚 γ-谷氨酸 (γ-PGA) 与三聚磷酸盐 (TPP) 和MgSO(4) (多离子交联np) 混合组成的pH响应纳米颗粒，并对其进行了表征，以确定其在胰岛素口服递送中的有效性。没有TPP和MgSO(4) (NPs) 的同类产品被用作对照。Ft-ir和XRD结果表明，CS，胰岛素，γ-PGA，MgSO(4) 和TPP之间的自发相互作用可以形成离子交联的网络结构，从而导致纳米颗粒的形成。多离子交联的np比np更紧凑，而其zeta电位值可比。在储存过程中，悬浮在去离子水中的多离子交联np稳定至少10周。与NPs相比，多离子交联的NPs在更宽的pH范围内具有优异的稳定性。在体外释放研究中，与多离子交联的np相比，NPs未能在溶解介质中充分保留负载的胰岛素。跨上皮电阻和转运实验表明，多离子交联的NPs比NPs更有效地转运胰岛素; 共聚焦可视化进一步验证了通过细胞旁途径增强的胰岛素渗透。上述结果表明，多离子交联的np是改善小肠中胰岛素经粘膜递送的有前途的载体。

BACKGROUND & AIMS: :In a nanoplasmonic context, copper (Cu) is a potential and interesting surrogate to less accessible metals such as gold, silver or platinum. We demonstrate optical trapping of individual Cu nanoparticles with diameters between 25 and 70 nm and of two ionic Cu nanoparticle species, CuFe2O4 and CuZnFe2O4, with diameters of 90 nm using a near infrared laser and quantify their interaction with the electromagnetic field experimentally and theoretically. We find that, despite the similarity in size, the trapping stiffness and polarizability of the ferrites are significantly lower than those of Cu nanoparticles, thus inferring a different light-particle interaction. One challenge with using Cu nanoparticles in practice is that upon exposure to the normal atmosphere, Cu is spontaneously passivated by an oxide layer, thus altering its physicochemical properties. We theoretically investigate how the presence of an oxide layer influences the optical properties of Cu nanoparticles. Comparisons to experimental observations infer that oxidation of CuNPs is minimal during optical trapping. By finite element modelling we map out the expected temperature increase of the plasmonic Cu nanoparticles during optical trapping and retrieve temperature increases high enough to change the catalytic properties of the particles.

背景与目标： : 在纳米等离子体的背景下，铜 (Cu) 是一种潜在且有趣的替代物，可以替代不易接近的金属，例如金，银或铂。我们证明了使用近红外激光对直径在25至70  nm之间的单个Cu纳米颗粒以及直径为90  nm的两种离子Cu纳米颗粒物种CuFe2O4和CuZnFe2O4的光学捕获，并通过实验和理论上量化了它们与电磁场的相互作用。我们发现，尽管尺寸相似，但铁氧体的俘获刚度和极化率明显低于Cu纳米颗粒，从而推断出不同的光粒子相互作用。在实践中使用Cu纳米颗粒的一个挑战是，在暴露于正常大气中，Cu会被氧化物层自发钝化，从而改变其理化性质。我们从理论上研究了氧化物层的存在如何影响Cu纳米颗粒的光学性能。与实验观察结果的比较表明，在光学捕获过程中，CuNPs的氧化最小。通过有限元建模，我们绘制出了等离子体Cu纳米颗粒在光学捕获过程中的预期温度升高，并且回收温度升高到足以改变颗粒的催化性能。

BACKGROUND & AIMS: :Biological synthesis of nanoparticles is a growing research trend because it has numerous applications in pharmaceutics and biomedicine. The aim of this study was to obtain silver nanoparticles (AgNPs) from Bacillus sp. KFU36, a marine strain, and to assess its anticancer activity. The supernatant of Bacillus sp. KFU36 was supplemented with silver nitrate and the nanoparticles obtained were characterized spectrophotometrically and microscopically. A band of surface plasmon resonance was appeared at 430 nm, as revealed by UV-vis spectrophotometry. X-ray diffraction spectrum and Energy Dispersive Spectroscopy confirmed the crystalline and metallic structure of the AgNPs, respectively. Scanning electron microscopy revealed that the shape of the synthesized AgNPs were spherical and the size extended between 5 and 15 nm. The AgNPs were investigated for their potential anticancer effects on the cell viability, migration and apoptosis using MTT and wound-healing assays, and flow cytometry, respectively. The cytotoxic effects of these nanoparticles were evidenced by the decreasing the cell viability (as 15% at 50 μg/ml), cell density, adhesion capacity and losing the normal shape and size, and inducing the apoptosis on MCF-7 by 61% at 50 μg/ml. These findings confirm that the synthesized AgNPs exhibited superior anticancer activities and therefore could be exploited as a promising, cost-effective, and environmentally benign strategy in treating this disease in future.

背景与目标： 纳米颗粒的生物合成是一个日益发展的研究趋势，因为它在药剂学和生物医学中有许多应用。这项研究的目的是从海洋芽孢杆菌属KFU36中获得银纳米颗粒 (AgNPs)，并评估其抗癌活性。在芽孢杆菌属的上清液中添加了硝酸银，并通过分光光度法和显微镜对获得的纳米颗粒进行了表征。如通过UV-vis分光光度法所揭示的，在430 nm处出现了表面等离子体共振带。X射线衍射光谱和能量色散光谱分别证实了AgNPs的晶体和金属结构。扫描电子显微镜显示，合成的agnp的形状为球形，尺寸在5至15 nm之间扩展。分别使用MTT和伤口愈合试验以及流式细胞术研究了AgNPs对细胞活力，迁移和凋亡的潜在抗癌作用。这些纳米颗粒的细胞毒性作用通过降低细胞活力 (以50 μ g/ml 15%) 、细胞密度、粘附能力和失去正常形状和大小，以及以50 μ g/ml 61% 诱导MCF-7凋亡来证明。这些发现证实了合成的AgNPs具有出色的抗癌活性，因此可以作为将来治疗该疾病的有前途，具有成本效益且对环境无害的策略。