• 【代谢谱分析揭示了由二氧化钛纳米颗粒诱导的小鼠成纤维细胞碳水化合物代谢紊乱。】 复制标题 收藏 收藏
    DOI:10.1002/jat.2808 复制DOI
    作者列表:Jin C,Liu Y,Sun L,Chen T,Zhang Y,Zhao A,Wang X,Cristau M,Wang K,Jia W
    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))纳米颗粒广泛用于商业用途,因此需要充分说明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)及其相应培养基中代谢物谱的变化,并使用气相色谱仪对时间和时间进行了分析,研究了均质和弱聚集的(<100 nm)TiO(2)纳米颗粒的细胞毒性。飞行质谱(GC / TOFMS)的代谢组学策略。通过多变量统计分析,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,通过比较TiO(2)纳米粒子处理过的L929细胞或它们相应的培养基与对照组之间的差异,可以鉴定出一系列差异代谢产物。发现在TiO(2)纳米粒子处理的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中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,因此对于理解其潜在的分子机制非常有帮助。
  • 【三种标记的二氧化硅纳米粒子在多孔介质中的传输实验中用作示踪剂的比较。第一部分:合成与表征。】 复制标题 收藏 收藏
    DOI:10.1016/j.envpol.2013.07.031 复制DOI
    作者列表:Vitorge E,Szenknect S,Martins JM,Barthès V,Auger A,Renard O,Gaudet JP
    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粒子的合成与表征。研究了三种不同的标记策略:嵌入硅胶基质中的荧光有机分子(FITC),重金属核(Ag(0))和被硅胶壳包围的放射性核((110m)Ag)。确定了每种标记纳米粒子的主要性质和适用性,包括尺寸,表面性质,稳定性,检测限度和成本,并就其在运输研究中的用途进行了比较。荧光标记被发现是最方便,最便宜的方法,但是化学(Ag(0))和放射性标记的((110m)Ag)纳米颗粒达到了最佳的检测限,这也允许无损定量。这项工作表明,选择标记的纳米颗粒作为天然胶体替代物还是人造纳米颗粒,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规模。
  • 【双重功能基质金属蛋白酶响应姜黄素负载纳米颗粒用于肿瘤靶向治疗。】 复制标题 收藏 收藏
    DOI:10.1080/10717544.2019.1676843 复制DOI
    作者列表:Guo F,Fu Q,Jin C,Ji X,Yan Q,Yang Q,Wu D,Gao Y,Hong W,Li A,Yang G
    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: :抗癌药的局限性包括不良的肿瘤靶向性和较弱的摄取效率,是影响肿瘤治疗的重要因素。根据肿瘤微环境的特征,本研究旨在基于两亲嵌段共聚物(MePEG-Peptide-PET-PCL)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)。 ),可修饰MMP裂解肽(GPLGIAGQ)和穿透肽(r9),以改善肿瘤靶向性和细胞摄取。 Cur-P-NPs的平均大小为176.9 nm,ζ电位为8.1 mV,显示出药物的包封率和载药量分别为87.07%±0.63%和7.44%±0.16%。此外,在pH 7.4下,Cur-P-NPs的Cur释放持续了144 wash,并且在酶反应条件下加速了释放速率。 MTT分析表明,游离的P-NP具有良好的生物安全性,Cur-P-NP的抗增殖活性与MCF-7细胞中的Cur浓度呈正相关。另外,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,从而在肿瘤治疗中产生了最佳的生物利用度。因此,Cur-P-NP作为一种有前途的药物递送系统,可能会为临床实践中的靶向治疗带来新的有效途径。
  • 【载有阿霉素的PLGA纳米颗粒用于胶质母细胞瘤的化学疗法:药物开发。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2019.118733 复制DOI
    作者列表:
    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: :纳米粒子脑部给药是一种很有前途的策略,可以为脑肿瘤化疗开辟新的可能性。如先前的研究所示,阿霉素在涂有泊洛沙姆188(Dox-PLGA)的聚(丙交酯-共-乙交酯)纳米颗粒中的负载量使这种细胞抑制剂能够以大脑的形式传递,而后者通常无法以自由形式穿透血脑屏障。 Dox-PLGA纳米粒子对大鼠颅内101.8胶质母细胞瘤产生了非常显着的抗肿瘤作用,因此代表了有希望进行临床评估的脑肿瘤化学疗法的有希望的候选者。因此,本研究的目的是优化Dox-PLGA配方并开发中试规模的制造工艺。制备程序的优化涉及改变工艺参数,例如用可能更安全的低分子量PVA 9-10kDa代替颗粒稳定剂PVA 30-70kDa,以及外部乳液介质的改性和均质化条件。优化的程序可以将包封效率从66%提高到> 90%,并将纳米颗粒的尺寸从250nm减小到110nm,从而可以通过膜过滤进行灭菌。中试规模工艺的特点是具有出色的重现性,并且批间差异非常小。在治疗相关浓度下,纳米粒子的体外血液毒性可忽略不计。通过体内实验证实了优化制剂的抗肿瘤功效以及纳米颗粒渗透入颅内肿瘤和正常脑组织的能力。
  • 【一种基于ssDNA适体和金纳米颗粒的快速,简便,灵敏的检测含His标签的几丁质酶的方法。】 复制标题 收藏 收藏
    DOI:10.1016/j.foodchem.2020.127230 复制DOI
    作者列表:Cao Z,Wang S,Liu Z,Xue C,Mao X
    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。几丁质是一种N-乙酰氨基葡萄糖的长链聚合物,是葡萄糖的衍生物,可通过应用几丁质酶分解糖苷键形成壳寡糖来水解。异源基因表达产生的几丁质酶通常与6×His标签相连,以方便纯化。与6×His-tag连接的异源几丁质酶是一种转基因元件,但是酶活性测试不能用于区分转基因元件和天然元件。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适体来检测含His标签的几丁质酶。使用这种方法,可以在5分钟内以低至0.136nM的浓度检测到含His-tag的几丁质酶。 AuNPs的颜色变化与含His标签的几丁质酶浓度呈正相关。
  • 【体内氧化铁Fe3O4纳米颗粒与肺泡巨噬细胞的相互作用。】 复制标题 收藏 收藏
    DOI:10.1007/s10517-012-1593-z 复制DOI
    作者列表:Katsnelson BA,Privalova LI,Sutunkova MP,Tulakina LG,Pichugova SV,Beykin JB,Khodos MJ
    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: :将气管内施用初级直径为10 nm的磁铁矿纳米颗粒的水悬浮液注入大鼠肺中。在24小时内,从支气管肺泡灌洗液中分离细胞,并在透射电子显微镜下检查。肺泡巨噬细胞显示出能够主动摄取单个纳米颗粒和由此类颗粒组成的小聚集体的能力,然后这些小聚集体会在融合的吞噬体内形成较大的团块。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cr和线粒体膜紧密相互作用,从而对这些细胞内结构造成了明显的破坏。初级溶酶体的损失可被视为间接证据,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发挥了作用。
  • 【探索多西紫杉醇棕榈酸酯及其固体脂质纳米颗粒,作为减轻对多药耐药性的关注的新选择。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2020.119088 复制DOI
    作者列表:Kaushik L,Srivastava S,Panjeta A,Chaudhari D,Ghadi R,Kuche K,Malik R,Preet S,Jain S,Raza K
    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: :多西他赛(DTX)是一种广泛使用的抗癌药,现在与多药耐药性增加有关。另外,作为有问题的BCS IV类药物,它对配方设计师提出了挑战。今后,可以设想与生物相容性脂质即棕榈酸合成DTX的类似物。硅内研究(分子对接和模拟)推断多西他赛棕榈酸酯(DTX-PL)与P-gp相对于DTX和紫杉醇的结合较少,表明它是P-gp外排的不良底物。使用各种脂质制备缀合物的固体脂质纳米颗粒(SLN)。棕榈酸,硬脂酸,棕榈酸十六烷基酯和单硬脂酸甘油酯。进行了纳米载体的表征研究,包括表面电荷,药物有效载荷,微分子论,药物释放模式和表面形态。从对抗性MCF-7细胞的细胞毒性试验中可以确定,新的类似物提供的IC50较DTX大大降低。此外,凋亡测定法也证实了在IC 50测定中获得的结果,其中SA-SLNs显示出比游离DTX最高的凋亡指数。该缀合物不仅提高了溶解度,而且还提供了较低的血浆蛋白结合力,并在适合的动物模型中改善了载有DTX的SA-SLN的药代动力学和药效学作用,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,并为在纳米版本中获得更安全,有效的癌症化学疗法的更好的候选药物带来了一线希望。
  • 【具有pH响应特性的多离子交联纳米颗粒,用于蛋白质药物的口服给药。】 复制标题 收藏 收藏
    DOI:10.1016/j.jconrel.2008.08.020 复制DOI
    作者列表:Lin YH,Sonaje K,Lin KM,Juang JH,Mi FL,Yang HW,Sung HW
    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)(多离子交联的NPs)混合而成的pH响应纳米颗粒在口服胰岛素中。没有TPP和MgSO(4)(NPs)的对应物用作对照。 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,而它们的ζ电位值却相当。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NP相比,多离子交联的NP在更宽的pH范围内具有出色的稳定性。在体外释放研究中,与多离子交联的NP相比,NP在溶解介质中未能提供足够的负载胰岛素保留。跨上皮电阻和转运实验表明,多离子交联的NPs转运胰岛素的效率明显高于NPs。共聚焦可视化进一步证实了胰岛素通过细胞旁途径的渗透性增强。前述结果表明,多离子交联的NP是改善小肠中胰岛素经粘膜递送的有希望的载体。
  • 【光学陷阱揭示了铜纳米颗粒与其氧化物和铁氧体相比在介电和光学性质上的差异。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-020-57650-2 复制DOI
    作者列表:Purohit P,Samadi A,Bendix PM,Laserna JJ,Oddershede LB
    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)是潜在的有趣替代物,是诸如金,银或铂之类难于接触的金属的替代品。我们演示了使用近红外激光对直径在25至70 nm之间的单个Cu纳米颗粒以及两种离子型Cu纳米颗粒CuFe2O4和CuZnFe2O4进行光阱捕获的过程,直径分别为90 nm,并在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显着低于Cu纳米粒子,因此推断出不同的光粒子相互作用。在实践中使用铜纳米粒子的一个挑战是,暴露于正常大气后,铜会被氧化层自然钝化,从而改变其物理化学性质。我们从理论上研究了氧化物层的存在如何影响Cu纳米粒子的光学性能。与实验观察结果的比较表明,在光阱过程中,CuNPs的氧化作用极小。通过有限元建模,我们可以绘制出在光捕获过程中等离激元Cu纳米粒子的预期温度升高情况,并且检索到的温度升高幅度足以改变颗粒的催化性能。
  • 【芽孢杆菌KFU36合成的银纳米颗粒及其通过诱导凋亡机制在乳腺癌MCF-7细胞中的抗癌作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.jphotobiol.2020.111786 复制DOI
    作者列表:Almalki MA,Khalifa AYZ
    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种日益增长的研究趋势,因为它在制药和生物医学领域具有广泛的应用。这项研究的目的是从芽孢杆菌中获得银纳米颗粒(AgNPs)。 KFU36,一种海洋菌株,并评估其抗癌活性。芽孢杆菌属的上清液。 KFU36补充有硝酸银,并用分光光度法和显微镜对得到的纳米颗粒进行了表征。紫外可见分光光度法显示,在430 nm处出现了一条表面等离振子共振带。 X射线衍射光谱和能量分散光谱法分别证实了AgNP的晶体和金属结构。扫描电子显微镜显示合成的AgNPs的形状为球形,大小在5至15 nm之间。分别使用MTT和伤口愈合试验以及流式细胞仪研究了AgNP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(在50μg/ ml时为15%),细胞密度,黏附能力和失去正常形状和大小以及在60°C诱导MCF-7凋亡的61%来证明。 50微克/毫升这些发现证实了合成的AgNPs表现出优异的抗癌活性,因此可以被用作未来治疗该疾病的有希望的,具有成本效益的和环境友好的策略。
  • 【基于羧甲基纤维素的威化饼富含白藜芦醇负载的纳米颗粒,可增强伤口愈合能力。】 复制标题 收藏 收藏
    DOI:10.1007/s13346-020-00711-w 复制DOI
    作者列表:Amanat S,Taymouri S,Varshosaz J,Minaiyan M,Talebi A
    BACKGROUND & AIMS: :The present study aimed to prepare and investigate the wound healing potential of carboxymethyl cellulose (CMC)-based wafers incorporated with resveratrol (RSV)-loaded cellulose acetate butyrate (CAB) NPs. Accordingly, RSV-CAB NPs were prepared using the solvent evaporation method. The effect of different formulation parameters (polymer content, surfactant concentration, and the volume ratio of aqueous phase to organic phase) on the properties of NPs was investigated using the Box-Behnken design. Then, the optimized NPs were incorporated in wafers comprising CMC combined with hydroxyl propyl methyl cellulose (HPMC) or chitosan. Hydration capacity, porosity, adhesive strength, and hardness of the prepared nanocomposite wafers were examined. Optimized formulation was spherical, showing the particle size, polydispersity index, zeta potential, encapsulation efficiency %, drug loading %, and release efficiency % of 248.5 nm, 0.38, - 1.59, 87.58, 25.94, and 67.10, respectively. The CMC-HPMC wafers exhibited higher porosity, hydration capacity, and adhesive performance, as compared with the CMC wafers alone and CMC-chitosan wafers. Wound healing test and histological evaluation in the excisional wounds of the rats showed that the RSV-NPs-wafers were more effective as a healing accelerator, in comparison to wafers without drug or those containing the free RSV. These results demonstrated the potential of the RSV-NPs-wafer in wound healing drug delivery applications. Graphical abstract.
    背景与目标: :本研究旨在准备和研究结合了白藜芦醇(RSV)的醋酸丁酸纤维素(CAB)NP的基于羧甲基纤维素(CMC)的晶圆的伤口愈合潜力。因此,使用溶剂蒸发法制备了RSV-CAB NP。使用Box-Behnken设计研究了不同配方参数(聚合物含量,表面活性剂浓度以及水相与有机相的体积比)对NPs性能的影响。然后,将优化的NP掺入包含CMC和羟丙基甲基纤维素(HPMC)或壳聚糖的晶片中。检查了制备的纳米复合晶片的水合能力,孔隙率,粘合强度和硬度。优化的配方是球形的,分别显示了248.5 nm,0.38,-1.59、87.58、25.94和67.10的粒径,多分散指数,ζ电位,包封率%,载药率和释放效率%。与单独使用CMC晶片和CMC-壳聚糖晶片相比,CMC-HPMC晶片显示出更高的孔隙率,水合能力和粘合性能。大鼠切除伤口的伤口愈合测试和组织学评估表明,与没有药物的晶片或含有游离RSV的晶片相比,RSV-NPs晶片作为愈合促进剂更有效。这些结果证明了RSV-NPs晶片在伤口愈合药物递送应用中的潜力。图形概要。
  • 【靶向丝裂霉素C负载和LDL共轭的介孔二氧化硅纳米粒子的靶向递送,用于抑制翼状sub肉结膜下成纤维细胞的增殖。】 复制标题 收藏 收藏
    DOI:10.1016/j.exer.2020.108124 复制DOI
    作者列表:Wu M,Wang S,Wang Y,Zhang F,Shao T
    BACKGROUND & AIMS: :Pterygium is a degenerative disease that characterized by excessive fibrovascular proliferation. To reduce the recurrence rate, surgery is the main strategy, in combination with adjacent procedures or adjunctive therapy. One of the most common adjunctive agents, mitomycin C (MMC), is known as an alkylating agent that inhibits fibroblast proliferation but is limitedly applied in pterygium due to various complications. A previous study demonstrated that activated pterygium subconjunctival fibroblasts overexpressed low-density lipoprotein (LDL) receptors. In this study, we designed and synthesized MMC-loaded mesoporous silica nanoparticles conjugated with LDL (MMC@MSNs-LDL) to deliver MMC into activated pterygium fibroblasts in a targeted manner. The MMC loading efficiency was approximately 6%. The cell viability test (CCK-8 assay) revealed no cytotoxicity for the empty carrier MSNs at a concentration of ≤1 mg/ml after administration for 48 h in subconjunctival fibroblasts. Primary pterygium and normal human subconjunctival fibroblasts with or without stimulation by vascular endothelial growth factor (VEGF) were treated as follows: 1) 10 μg/ml MMC@MSNs-LDL for 24 h (MMC concentration: 0.6 μg/ml); 2) 0.2 mg/ml MMC for 5 min then cultured for 24 h after MMC removal; and 3) normal culture without any drug treatment. At 24 h, the anti-proliferative effect of MMC@MSNs-LDL in activated pterygium fibroblasts was similar to that of MMC (cell viability: 46.2 ± 5.5% vs 40.5 ± 1.1%, respectively, P = 0.349). Furthermore, the cytotoxicity of MMC@MSNs-LDL to normal fibroblasts with or without VEGF stimulation was significantly lower than that of traditional MMC (cell viability: 75.6 ± 4.4% vs 36.0 ± 1.5%, respectively, P < 0.001; 84.7 ± 5.5% vs 35.7 ± 1.3%, P < 0.001). The binding of fluorescently labeled MMC@MSNs-LDL in fibroblasts was assessed using confocal fluorescence microscopy. The uptake of targeted nanoparticles in fibroblasts was time dependent and saturated at 6 h. VEGF-activated pterygium fibroblasts showed more uptake of MMC@MSNs-LDL than normal fibroblasts with or without VEGF activation (both P < 0.001). Our data strongly suggest that MMC@MSNs-LDL had an effective antiproliferative role in activated pterygium fibroblasts, with reduced toxicity to normal fibroblasts compared to traditional application of MMC. LDL-mediated drug delivery might have great potential in the management of pterygium recurrence.
    背景与目标: :翼状is肉是一种退化性疾病,其特征是过度的血管血管增生。为了降低复发率,手术是主要策略,并与邻近的手术或辅助治疗相结合。最常见的辅助剂之一,丝裂霉素C(MMC),是一种抑制成纤维细胞增殖的烷基化剂,但由于各种并发症,其在翼状ery肉中的应用受到限制。先前的研究表明,激活的结膜下翼状ery肉成纤维细胞过度表达了低密度脂蛋白(LDL)受体。在这项研究中,我们设计并合成了与LDL(MMC @ MSNs-LDL)共轭的MMC负载的介孔二氧化硅纳米粒子,以靶向方式将MMC传递到活化的翼状fi肉成纤维细胞中。 MMC的加载效率约为6%。细胞存活力测试(CCK-8分析)显示,结膜下成纤维细胞给药48小时后,≤1mg / ml的空载体MSNs没有细胞毒性。对有或没有血管内皮生长因子(VEGF)刺激的原发性翼状and肉和正常人结膜下成纤维细胞进行如下处理:1)10μg/ ml MMC @ MSNs-LDL持续24 h(MMC浓度:0.6μg/ ml); 2)MMC 0.2 mg / ml持续5分钟,MMC去除后培养24小时; 3)未经任何药物处理的正常培养。在24小时时,MMC @ MSNs-LDL在活化的翼状fi肉成纤维细胞中的抗增殖作用与MMC相似(细胞活力分别为46.2±5.5%和40.5±1.1%,P = 0.349)。此外,MMC @ MSNs-LDL对有或没有VEGF刺激的正常成纤维细胞的细胞毒性显着低于传统MMC(细胞活力分别为75.6±4.4%和36.0±1.5%,P <0.001; 84.7±5.5% vs 35.7±1.3%,P <0.001)。使用共聚焦荧光显微镜评估成纤维细胞中荧光标记的MMC @ MSNs-LDL的结合。成纤维细胞中靶向纳米粒子的吸收是时间依赖性的,并在6小时后达到饱和。 VEGF激活的翼状fi肉成纤维细胞比具有或不具有VEGF激活的正常成纤维细胞显示更多的MMC @ MSNs-LDL摄取(P均<0.001)。我们的数据强烈表明MMC @ MSNs-LDL在活化的翼状肉成纤维细胞中具有有效的抗增殖作用,与传统的MMC应用相比,对正常成纤维细胞的毒性降低。 LDL介导的药物递送在翼状re肉复发的治疗中可能具有巨大的潜力。
  • 【氧化铜纳米粒子对两种甘薯植物的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.plaphy.2020.06.009 复制DOI
    作者列表:Bonilla-Bird NJ,Ye Y,Akter T,Valdes-Bracamontes C,Darrouzet-Nardi AJ,Saupe GB,Flores-Marges JP,Ma L,Hernandez-Viezcas JA,Peralta-Videa JR,Gardea-Torresdey JL
    BACKGROUND & AIMS: :Little information is available on the interaction of CuO nanoparticles (nCuO) with tuberous roots. In this study, Beauregard-14 (B-14, low lignin) and Covington (COV, high lignin) sweetpotato varieties were cultivated until maturity in soil amended with nCuO, bulk copper oxide (bCuO) and CuCl2 at 25-125 mg/kg. The Cu treatments had no significant influence on chlorophyll content. Gas exchange parameters were not affected in B-14. In COV, however, at 125 mg/kg treatments, bCuO reduced the intercellular CO2 (11%), while CuCl2 increased it by 7%, compared with control (p ≤ 0.035). At 25 mg/kg nCuO increased the length of COV roots (20.7 ± 2.0 cm vs. 14.6 ± 0.8 cm, p ≤ 0.05). In periderm of B-14, nCuO, at 125 mg/kg, increased Mg by 232%, while the equivalent concentration of CuCl2 reduced P by 410%, compared with control (p ≤ 0.05). The data suggest the potential application of nCuO as nanofertilizer for sweetpotato storage root production.
    背景与目标: :关于CuO纳米颗粒(nCuO)与块根的相互作用的信息很少。在这项研究中,培育了Beauregard-14(B-14,低木质素)和Covington(COV,高木质素)甘薯品种,直到在土壤中用nCuO,块状氧化铜(bCuO)和CuCl2修正的成熟度为25-125 mg / kg 。铜处理对叶绿素含量无显着影响。气体交换参数在B-14中不受影响。然而,在COV中,以125 mg / kg的剂量处理,与对照相比,bCuO减少了细胞间CO2(11%),而CuCl2则增加了7%(p≤0.035)。在25 mg / kg nCuO下,COV根的长度增加了(20.7±2.0 cm对14.6±0.8 cm,p≤0.05)。与对照相比,在B-14的外皮中,nCuO在125 mg / kg时使Mg增加232%,而当量的CuCl2则使P减少410%(p≤0.05)。数据表明,nCuO作为甘薯贮藏根生产的纳米肥料的潜在应用。
  • 【面包果种子提取物的绿色合成银纳米颗粒及其抗菌活性。】 复制标题 收藏 收藏
    DOI:10.2174/1389201021666200107115849 复制DOI
    作者列表:Shobana S,Veena S,Sameer SSM,Swarnalakshmi K,Vishal LA
    BACKGROUND & AIMS: AIMS:To evaluate the antibacterial activity of Artocarpus hirsutus mediated seed extract for nanoparticle synthesis. BACKGROUND:Gastrointestinal bacteria are known for causing deadly infections in humans. They also possess multi-drug resistance and interfere with clinical treatments. Applied nanotechnology has been known to combat such infectious agents with little interference from their special attributes. Here we synthesize silver nanoparticles from Artocarpus hirsutus seed extract against two gastro-intestinal bacterial species: Enterobacter aerogenes and Listeria monocytogenes. OBJECTIVE:To collect, dry, and process seeds of Artocarpus hirsutus for nanoparticle synthesis. To evaluate the morphological interaction of silver nanoparticles with bacteria. METHODS:Artocarpus hirsutus seeds were collected and processed and further silver nanoparticles were synthesized by the co-precipitation method. The synthesized nanoparticles were characterized using XRD, UV, FTIR, and SEM. These nanoparticles were employed to study the antibacterial activity of nanoparticles against Enterobacter aerogenes and Listeria monocytogenes using well diffusion method. Further, morphological interaction of silver nanoparticles on bacteria was studied using SEM. RESULTS:Silver nanoparticles were synthesized using Artocarpus hirsutus seed extract and characterization studies confirmed that silver nanoparticles were spherical in shape with 25-40 nm size. Antibacterial study exhibited better activity against Enterobacter aerogenes with a maximum zone of inhibition than on Listeria monocytogenes. SEM micrographs indicated that Enterobacter aerogenes bacteria were more susceptible to silver nanoparticles due to the absence of cell wall. Also, the size and charge of silver nanoparticles enable easy penetration of the bacterial cell wall. CONCLUSION:In this study, silver nanoparticles were synthesized using the seed extract of Artocarpus hirsutus for the first time exploiting the fact that Moraceae species have high phytonutrient content which aided in nanoparticle synthesis. This nanoparticle can be employed for large scale synthesis which when coupled with the pharmaceutical industry can be used to overcome the problems associated with conventional antibiotics to treat gastrointestinal bacteria.
    背景与目标: 目的:评价面包果介导的种子提取物对纳米粒子合成的抗菌活性。
    背景:胃肠道细菌已知会导致人类致命的感染。它们还具有多药耐药性并干扰临床治疗。已知应用纳米技术可在不受其特殊属性干扰的情况下与此类传染源抗争。在这里,我们从面包果种子提取物中合成了针对两种胃肠道细菌的银纳米颗粒:产气肠杆菌和单核细胞增生李斯特菌。
    目的:收集,干燥和加工面包果种子进行纳米颗粒合成。评估银纳米粒子与细菌的形态相互作用。
    方法:收集和处理面包果种子,并通过共沉淀法合成银纳米颗粒。使用XRD,UV,FTIR和SEM对合成的纳米颗粒进行表征。这些纳米颗粒被用于通过良好扩散方法研究纳米颗粒对产气肠杆菌和单核细胞增生性李斯特菌的抗菌活性。此外,使用SEM研究了银纳米颗粒在细菌上的形态相互作用。
    结果:利用面包果种子提取物合成了银纳米颗粒,表征研究证实银纳米颗粒为球形,尺寸为25-40 nm。抗菌研究显示,与单核细胞增生李斯特菌相比,对产气肠杆菌具有最大的抑制作用,具有更好的活性。 SEM显微照片表明,由于不存在细胞壁,所以产气肠杆菌对银纳米颗粒更敏感。而且,银纳米颗粒的大小和电荷使细菌细胞壁易于渗透。
    结论:在这项研究中,利用禾本科物种具有高植物营养素含量的事实,首次利用面包果种子提取物合成了银纳米颗粒。该纳米颗粒可用于大规模合成,当与制药工业结合使用时,可用于克服与常规抗生素相关的治疗胃肠道细菌的问题。
  • 【载有阿法替尼的可吸入PLGA纳米颗粒用于非小细胞肺癌(NSCLC)发育和体外疗效的局部治疗。】 复制标题 收藏 收藏
    DOI:10.1007/s13346-020-00802-8 复制DOI
    作者列表:Elbatanony RS,Parvathaneni V,Kulkarni NS,Shukla SK,Chauhan G,Kunda NK,Gupta V
    BACKGROUND & AIMS: :Afatinib (AFA) is a potent aniline-quinazoline derivative, approved by the Food and Drug Administration (FDA) in 2013, as a first-line treatment for metastatic non-small cell lung cancer (NSCLC). However, its clinical application is highly limited by its poor solubility, and consequently low bioavailability. We hypothesize that loading of AFA into biodegradable PLGA nanoparticles for localized inhalational drug delivery will be instrumental in improving therapeutic outcomes in NSCLC patients. Formulated AFA nanoparticles (AFA-NP) were evaluated for physicochemical properties (particle size: 180.2 ± 15.6 nm, zeta potential: - 23.1 ± 0.2 mV, % entrapment efficiency: 34.4 ± 2.3%), formulation stability, in-vitro aerosol deposition behavior, and anticancer efficacy. Stability studies revealed the physicochemical stability of AFA-NP. Moreover, AFA-NP exhibited excellent inhalable properties (mass median aerodynamic diameter (MMAD): 4.7 ± 0.1 μm; fine particle fraction (FPF): 77.8 ± 4.3%), indicating efficient particle deposition in deep lung regions. With respect to in-vitro drug release, AFA-NP showed sustained drug release with cumulative release of 56.8 ± 6.4% after 48 h. Cytotoxic studies revealed that encapsulation of AFA into PLGA nanoparticles significantly enhanced its cytotoxic potential in KRAS-mutated NSCLC cell lines (A549, H460). Cellular uptake studies revealed enhanced internalization of coumarin-loaded nanoparticles compared to plain coumarin in A549. In addition, 3D tumor spheroid studies demonstrated superior efficacy of AFA-NP in tumor penetration and growth inhibition. To conclude, we have established in-vitro efficacy of afatinib-loaded PLGA nanoparticles as inhalable NSCLC therapy, which will be of great significance when designing preclinical and clinical studies. Graphical abstract.
    背景与目标: :Afatinib(AFA)是一种有效的苯胺-喹唑啉衍生物,于2013年获得美国食品药品监督管理局(FDA)批准,是转移性非小细胞肺癌(NSCLC)的一线治疗药物。然而,由于其不良的溶解性以及因此低的生物利用度,其临床应用受到了极大的限制。我们假设将AFA加载到可生物降解的PLGA纳米颗粒中以进行局部吸入药物输送,将有助于改善NSCLC患者的治疗效果。评价了配制的AFA纳米颗粒(AFA-NP)的理化性质(粒径:180.2±15.6nm,ζ电位:-23.1±0.2mV,包封率%:34.4±2.3%),制剂稳定性,体外气溶胶沉积行为,并具有抗癌功效。稳定性研究揭示了AFA-NP的理化稳定性。此外,AFA-NP表现出优异的可吸入特性(质量空气动力学中位直径(MMAD):4.7±0.1μm;细颗粒分数(FPF):77.8±4.3%),表明在深肺区域有效的颗粒沉积。关于体外药物释放,AFA-NP在48小时后显示出持续的药物释放,累积释放为56.8±6.4%。细胞毒性研究表明,将AFA封装到PLGA纳米颗粒中可显着增强其在KRAS突变的NSCLC细胞系(A549,H460)中的细胞毒性潜能。细胞摄取研究显示,与普通A549香豆素相比,香豆素负载的纳米颗粒的内在化增强。此外,3D肿瘤球体研究证明AFA-NP在肿瘤渗透和生长抑制方面具有出色的功效。总而言之,我们已经建立了载有阿法替尼的PLGA纳米颗粒作为可吸入NSCLC治疗的体外疗效,这在设计临床前和临床研究时将具有重要意义。图形概要。

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