PEG-G5.NH2-FITC-DOTA(Gd)-Monalizumab/IPH4301探针的初步研究

摘要 目的：制备PEG-G5.NH2-FITC-DOTA(Gd)- Monalizumab/IPH4301纳米探针,并研究其与NK-92MI细胞的结合能力、毒性、细胞体外MRI成像能力、促进NK-92MI细胞对MDA-MB-231三阴性乳腺癌细胞的杀伤能力。方法：制备PEG-G5.NH2-FITC-DOTA(Gd)- Monalizumab/IPH4301纳米探针,利用透射电子显微镜（Transmission Electron Microscope,TEM）进行表征,并使用ImageJ对其粒径进行统计;通过流式细胞术分析纳米材料和NK-92MI细胞的结合能力;应用MRI对纳米探针标记的NK-92MI细胞体外成像并分析其T1加权（T1WI）的信号改变。利用蛋白印迹（Western blot）检测经过与NK-92MI细胞共培养后三阴性乳腺癌MDA-MB-231细胞凋亡相关蛋白的表达以及Elisa法检测培养体系内的IFN-γ的表达量。结果：制备的纳米探针颗粒粒径分布均匀,形态近似球形。其与NK-92MI细胞结合的量以及T1信号随着纳米探针浓度增加而逐渐增加。使用Monalizumab和IPH4301两种抗体修饰的纳米探针增强了NK-92MI细胞释放IFN-γ并促进MDA-MB-231乳腺癌细胞的凋亡。结论：PEG-G5.NH2-FITC-DOTA(Gd)-Monalizumab/IPH4301纳米探针在结合NK-92MI细胞后,可以在3.0T磁共振下进行体外成像,并增强了NK-92MI细胞对MDA-MB-231细胞的杀伤能力。     

VEGF靶向分子探针的制备及对卵巢癌细胞SKOV3体外成像的初步研究

目的:制备分子探针VEGF-USPIO和研究其在体外对卵巢癌细胞的靶向成像作用。方法:采用化学偶联法将VEGF抗体与USPIO连接,构建成具有免疫活性的靶向分子探针VEGF-USPIO。用CCK-8法检测该探针对卵巢癌细胞株SKOV3细胞活性的影响;普鲁士蓝染色法检测细胞磁性标记情况,并对经过标记的细胞进行体外磁共振成像,观察其对磁共振信号强度的影响。结果:成功合成了分子靶向探针VEGF-USPIO;当探针浓度在60μg/mL及以下时对细胞活性无影响(P0.05);细胞普鲁士蓝染色结果显示标记了靶向探针VEGF-USPIO的细胞其胞膜及胞浆含铁颗粒沉积较多;细胞体外磁共振成像结果显示经靶向探针标记的细胞,T2WI信号强度较未标记探针的对照组细胞降低(P0.05)。结论:所合成的VEGF-USPIO通过磁共振信号强度的变化实现MRI成像。     

RGD肽介导的MR分子探针在体外结直肠癌细胞的显像及对其生物学行为的影响

目的:探讨RGD肽介导的MR分子探针在体外结直肠癌细胞的MRI显像及对其生物学行为的影响方法:利用纳米技术构建靶向RGD荧光纳米MR探针,利用荧光倒置相差显微镜观察该探针与LOVO细胞结合情况;体外磁共振成像（MRI）显像;利用细胞克隆实验测其增殖活性;流式细胞术检测其细胞周期、凋亡。结果:荧光相差显微镜示该RGD肽介导的MR分子探针能特异性与LOVO细胞结合;体外MRI成像示靶向RGD组T₁信号强度高于非靶向组及对照组（P<0.05）;该探针作用24h后的LOVO细胞增殖活性降低,细胞分裂周期发生变化,阻滞在S+G₂M期的细胞比例上升,细胞凋亡率与其他两组相比有显著增加（P<0.05）结论:该RGD肽介导的MR分子探针能与结直肠癌LOVO细胞靶向结合,能增强MRI的显像效果,并对肿瘤细胞具有一定的抑制作用     

抗人精子蛋白17磁性纳米探针靶向的卵巢癌体内外磁共振成像

用MRI(magnetic resonance imaging)技术探索连接抗人精子蛋白17单克隆抗体(anti-Sp17 mAb)的磁性纳米探针对体外培养及动物体内Sp17+卵巢癌的靶向性。将anti-Sp17mAb连接到表面包覆壳聚糖的超顺磁性氧化铁纳米颗粒上,制成磁性纳米探针anti-Sp17-MNP,用作MRI阴性对比剂。将磁性纳米探针与Sp17+和Sp17-培养的肿瘤细胞共育,进行一系列体外磁共振成像实验。荷瘤小鼠尾静脉注射磁性纳米颗粒,用7T磁共振仪在体成像,观察肿瘤部位的信号变化,并用普鲁士蓝染色肿瘤组织切片,观察有无铁粒子聚集。体外MRI数据显示,anti-Sp17-MNP与细胞靶向结合,并与细胞共育2 h后,Sp17+HO-8910的T2*信号强度比Sp17-HepG2低2倍;anti-Sp17-MNP对肿瘤细胞的靶向作用可被重组人Sp17阻断。7T磁共振仪对动物在体肿瘤成像结果显示,感兴趣区因磁性纳米探针靶向聚集而导致信号降低,并经组织切片普鲁士蓝染色证实。本研究结果表明,用anti-Sp17抗体和新的合成路线制备的纳米探针具有用作MR对比剂进行分子成像的潜能。     

RGD肽介导的MR分子探针在体外结直肠癌细胞的显像及对其生物学行为的影响

目的：探讨RGD肽介导的MR分子探针在体外结直肠癌细胞的MRJ显像及对其生物学行为的影响。方法：利用纳米技术构建靶向RGD荧光纳米MR、探针,利用荧光倒置相、差显微镜观察该探针与LOVO细胞结合情况;体外磁共振成像（MRI）显像;利用细胞克隆实验测其增殖活性;流式细胞术检测其细胞周期、凋亡。结果：荧光相差显微镜示该RGD肽介导的MR分子探针能特异性与LOVO细胞结合;体外MRI成像示靶向RGD组T1信号强度高于非靶向组及对照组（P〈0．05）;该探针作用24h后的LOVO细胞增殖活性降低,细胞分裂周期发生变化,阻滞在S＋G2M期的细胞比例上升,细胞凋亡率与其他两组相比有显著增加（P〈0．05）。结论：该RGD肽介导的MR分子探针能与结直肠癌LOVO细胞靶向结合,能增强MR1的显像效果,并对肿瘤细胞具有一定的抑制作用．     

磁性Fe_3O_4/聚苯胺纳米纤维的制备及其固定漆酶研究

合成优良的漆酶固定化载体有利于其进一步应用。通过将磁性纳米颗粒包埋在苯胺的聚合物中形成磁性Fe_3O_4/聚苯胺纳米纤维,作为漆酶固定化载体。透射电镜和红外图谱分别显示了载体的形态结构特征。不同比例的Fe_3O_4与苯胺对载体结构没有明显影响,但会影响酶的负载量。合成载体最大酶负载量为210 mg/g,固定漆酶后的载体导电性能发生变化。固定化漆酶最适pH从4偏移到3.5,在酸性pH范围保持较高的酶活性,最适温度为60℃;在50℃下孵育240 min,能保持约50%的酶活性,于4℃下保存30 d能保持约60%的酶活性;重复使用8次后还能保留70%的酶活性;结果证实了磁性Fe_3O_4/聚苯胺纳米纤维成功合成,对酶有较高的负载量。随着Fe_3O_4的比例增加,载体对漆酶的负载量却减少;漆酶与载体间存在有一定电子交流。固定化漆酶的最适pH向酸性偏移可能和聚苯胺的导电性有关,合成载体显示出良好的热稳定性、储存稳定性和重复使用稳定性,表明磁性Fe_3O_4/聚苯胺纳米纤维是一种优良的酶固定化载体,可以实现酶的高效固定化。     

外加磁场作用下磁性Fe3O4纳米粒子对肝癌细胞增殖和凋亡的影响

目的:观察磁性四氧化三铁(Fe3O4)纳米粒子对肝癌细胞的体外作用,并研究外加稳恒磁场(SMF)或交变磁场(EMF)对Fe3O4纳米粒子作用的影响。方法:光镜下观察CBRH-7919细胞对Fe3O4纳米粒子的吞噬作用;MTT法检测Fe3O4纳米粒子对大鼠肝癌细胞株CBRH-7919的毒性及外加磁场的影响;流式细胞术检测外加磁场作用下Fe3O4纳米粒子对细胞凋亡及线粒体膜电位的影响。结果:光镜下可见CBRH-7919细胞吞噬大量Fe3O4纳米粒子入胞浆,且交变磁场作用下细胞的吞噬量增加。30～100μg/mL Fe3O4纳米粒子作用于CBRH-7919细胞未产生细胞毒性,稳恒磁场对其作用无影响,而交变磁场能增加Fe3O4纳米粒子的毒性,使细胞活性降低、凋亡率增加、线粒体膜电位降低。结论:交变磁场能增加CBRH-7919细胞对Fe3O4纳米粒子的吞噬并产生细胞毒性。     

紫杉醇对NK-92MI细胞杀伤功能及凋亡的影响

探讨紫杉醇对人自然杀伤细胞系NK-92MI细胞株杀伤活性及凋亡的影响。用不同浓度的紫杉醇处理NK.92MI细胞后,测定NK-92MI细胞的增殖率和对靶细胞的杀伤作用;同时检测NK·92MI细胞凋亡率及凋亡相关基因Bcl-2、Ba】【的表达。结果表明,紫杉醇可以抑制NK-92MI细胞增殖并且降低其杀伤活性,机制可能是通过诱导NK.92MI细胞的凋亡,而后者与Bcll2/Ba】【基因表达增高有关。     

探讨As2O3诱导人胃癌SGC-7901细胞凋亡过程中AKT相关 抗凋亡通路表达情况

目的:探讨三氧化二砷诱导胃癌细胞凋亡过程中,对AKT相关抗凋亡通路表达的影响。方法:分别用不同浓度(0μmol/L、7.5μmol/L、10μmol/L、12.5μmol/L和15μmol/L)三氧化二砷(As_2O_3)溶液处理胃癌细胞48 h,倒置显微镜观察细胞凋亡情况,并用Western blot方法检测p70S6kα、p-p70S6kα、p70S6kβ(S6蛋白激酶β,Ribosomal Protein S6 Kinaseβ)、p-p70S6kβ、rpS6、p-rpS6、p-BAD、BAD、p-GSK3β、GSK3β及NF-κB2等蛋白的表达情况与As_2O_3作用浓度之间的关系。结果:随As_2O_3作用细胞的浓度增大,p70S6kα、p-p70S6kα、p70s6kβ、p-p70S6kβ、p-BAD、p-GSK3β、NF-κB2蛋白的表达减少,rpS6、p-rpS6、GSK3β蛋白表达增多,各组间数据经统计学分析,P值均0.05,具有统计学意义。BAD蛋白的表达无明显改变,P0.05。结论:As_2O_3诱导人胃癌SGC-7901细胞凋亡机制中包括AKT相关的多个抗凋亡途径的激活,AKT在其中发挥重要作用。     

Fe-MOF纳米探针在乳腺癌光动力增敏铁死亡及MR激活成像中实验研究

摘要 目的：探讨肿瘤酸性微环境响应铁基金属有机框架（Iron-containing Metal Organic Frameworks, Fe-MOF）纳米探针对乳腺癌光动力增敏铁死亡及其体外MR T1激活效应。方法：制备Fe-MOF纳米探针,用透射电子显微镜（Transmission Electron Microscope, TEM）及原子力显微镜（Atomic Force Microscope, AFM）对其形态进行表征;采用3,3'',5,5''-四甲基联苯胺（TMB）及5,5''-二硫双（2-硝基苯甲酸）（DTNB）评价其在溶液水平ROS生成及GSH消耗能力;通过细胞毒性实验（MTT）测定纳米探针在暗毒性及光毒性条件下对4T1乳腺癌细胞的光动力增敏铁死亡的效能;将4T1细胞与Fe-MOF共孵育后,协同激光照射处理,使用荧光显微镜观察其活性氧（Reactive Oxygen Specis, ROS）、脂质过氧化物（Lipid PerOxide, LPO）的生成以及细胞活/死染色情况;观察纳米探针在不同的pH条件下T1加权成像的激活效应,并在细胞水平测量不同时间点的T1激活效能。结果：制备的Fe-MOF纳米探针呈针状结构,厚度约为44 nm;在体外溶液水平可有效促进ROS的生成及LPO的消耗;荧光显微镜结果显示Fe-MOF触发的铁死亡效应联合光动力治疗可有效促进细胞内ROS和LPO的生成,以及肿瘤细胞死亡率升高（P<0.001）;MR成像结果显示,在酸性条件下纳米探针的T1信号可被特异性激活,pH 5.0条件下r1弛豫率为4.954 mM^-1s^-1,具有较好pH响应性及细胞水平时间依赖性激活效能。结论：pH响应诊疗一体化的Fe-MOF纳米探针可实现乳腺癌的光动力增敏铁死亡效能以及MR微环境响应激活成像。     

巨噬细胞膜仿生纳米铁颗粒制备及多形性胶质母细胞瘤MRI成像的初步实验研究

摘要 目的：探讨巨噬细胞膜仿生的纳米铁颗粒（Fe3O4 NCs@MM）对多形性胶质母细胞瘤MRI成像的研究。方法：制备巨噬细胞膜仿生的纳米铁颗粒Fe₃O₄ NCs@MM,利用动态光散射（Dynamic Light Scattering,DLS）和透射电子显微镜（Transmission Electron Microscope,TEM）对其水合动力学粒径、表面电势和形态进行表征。采用SDS-聚丙烯酰胺凝胶电泳（sodium dodecyl sulphate-polyacrylamide gel electrophoresis,SDS-PAGE）评价巨噬细胞膜的完整包覆;紫外可见光谱测定巨噬细胞膜仿生的纳米铁颗粒抗蛋白吸附能力。通过MRI成像系统,分析了含不同浓度的Fe元素（0.1-1.6 mM）的Fe₃O₄ NCs@MM在GSH存在或不存在时的T₁弛豫效应。采用细胞增殖-毒性实验（Cell Counting Kit-8,CCK-8）,测定巨噬细胞膜仿生纳米铁颗粒处理肿瘤细胞24 h后的细胞活性。尾静脉注射巨噬细胞膜仿生纳米铁颗粒至原位胶质母细胞瘤模型中,观察成像效果。结果：巨噬细胞膜仿生的纳米铁颗粒Fe₃O₄ NCs@MM的水合动力学粒径和表面电势分别为 286.5±7.6 nm和-20.7±3.5 mV,且在水溶液中分布均匀,具有较好的单分散性。包覆巨噬细胞膜的纳米铁颗粒具备抗蛋白吸附的能力。MRI成像显示,制备的巨噬细胞膜仿生的纳米铁颗粒Fe₃O₄ NCs@MM为GSH响应型MRI对比剂,具有较好的T₁-加权磁共振成像效果,在尾静脉注射巨噬细胞膜的纳米铁颗粒0.5 h后,肿瘤部位的信号可见增强。结论：巨噬细胞膜仿生的纳米铁颗粒Fe₃O₄ NCs@MM可实现多形性胶质母细胞瘤的MRI成像。     

Irradiated chimeric antigen receptor engineered NK-92MI cells show effective cytotoxicity against CD19+ malignancy in a mouse model

Background aimsAnti-CD19 chimeric antigen receptor (CAR)-modified T cells have shown dramatic cytotoxicity against B-cell malignancies. Currently, autologous T cells are conventionally used to manufacture CAR T cells. Low quality or insufficient quantity of autologous T cells may lead to failure of CAR T preparations. Moreover, CAR T preparation usually takes 1–2 weeks, which is too long for patients with rapid disease progression to successfully infuse CAR T cells. Thus, the development of a ready-to-use CAR immunotherapy strategy is needed. NK-92, a natural killer (NK) cell line derived from an NK lymphoma patient, has been gradually applied as a CAR-modified effector cell. To avoid the potential development of secondary NK lymphoma in patients, large doses of radiation are used to treat NK-92 cells before clinical application, which ensures the safety but reduces the cytotoxicity of NK-92 cells. Therefore, it is crucial to explore a suitable radiation dose that ensures short life span and good cytotoxicity of CAR NK-92 cells.MethodsNK-92MI, a modified IL-2-independent NK-92 cell line, was used to establish an anti-CD19 CAR NK. The suitable radiation dose of CAR NK was then explored in vitro and validated in vivo, and the specific cytotoxicity of irradiated and unirradiated CAR NK against CD19⁺ malignant cells was assessed.ResultsCAR NK exhibited specific cytotoxicity against CD19⁺ malignant cells. Irradiation ensured a short life span of CAR NK in vitro and in vivo. Encouragingly, irradiated CAR NK displayed an anti-CD19⁺ malignancy capacity similar to that of unirradiated CAR NK.ConclusionsFive Gy is a suitable radiation dose to ensure the safety and effectiveness of CD19 CAR NK-92MI cells.     

Human CD56+ Cytotoxic Lung Lymphocytes Kill Autologous Lung Cells in Chronic Obstructive Pulmonary Disease

CD56+ natural killer (NK) and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD) are more cytotoxic to highly susceptible NK targets than those from control subjects. Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown. To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n = 60). First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44) on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+) cells. Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining. Lung NK cells (CD56+ CD3−) and CD56+ T cells (CD56+ CD3+) were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD. Lung NK cells had a predominantly “cytotoxic” CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV₁ % predicted decreased. Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV₁ % predicted. Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation. Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery. These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their potential role in emphysema progression.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00281229","term_id":"NCT00281229"}}NCT00281229     

Double-Layer Magnetic Nanoparticle-Embedded Silica Particles for Efficient Bio-Separation

Superparamagnetic Fe₃O₄ nanoparticles (NPs) based nanomaterials have been exploited in various biotechnology fields including biomolecule separation. However, slow accumulation of Fe₃O₄ NPs by magnets may limit broad applications of Fe₃O₄ NP-based nanomaterials. In this study, we report fabrication of Fe₃O₄ NPs double-layered silica nanoparticles (DL MNPs) with a silica core and highly packed Fe₃O₄ NPs layers. The DL MNPs had a superparamagnetic property and efficient accumulation kinetics under an external magnetic field. Moreover, the magnetic field-exposed DL MNPs show quantitative accumulation, whereas Fe₃O₄ NPs single-layered silica nanoparticles (SL MNPs) and silica-coated Fe₃O₄ NPs produced a saturated plateau under full recovery of the NPs. DL MNPs are promising nanomaterials with great potential to separate and analyze biomolecules.     

Comparative study of three magnetic nano-particles (FeSO4, FeSO4/SiO2, FeSO4/SiO2/TiO2) in plasmid DNA extraction

Recent updates on Magnetic Nano-Particles (MNPs) based separation of nucleic acids have received more attention due to their easy manipulation, simplicity, ease of automation and cost-effectiveness. It has been indicated that DNA molecules absorb on solid surfaces via hydrogen-bonding, and hydrophobic and electrostatic interactions. These properties highly depend on the surface condition of the solid support. Therefore, surface modification of MNPs may enhance their functionality and specification. In the present study, we functionalized Fe₃O₄ nano-particle surface utilizing SiO₂ and TiO₂ layer as Fe₃O₄/SiO₂ and Fe₃O₄/SiO₂/TiO₂ and then compare their functionality in the adsorption of plasmid DNA molecules with the naked Fe₃O₄ nano-particles. The result obtained showed that the purity and amount of DNA extracted by Fe₃O₄ coated by SiO₂ or SiO₂/TiO₂ were higher than the naked Fe₃O₄ nano-particles. Furthermore, we obtained pH 8 and 1.5 M NaCl as an optimal condition for desorption of DNA from MNPs. The result further showed that, 0.2 mg nano-particle and 10 min at 55 °C are the optimal conditions for DNA desorption from nano-particles. In conclusion, we recommended Fe₃O₄/SiO₂/TiO₂ as a new MNP for separation of DNA molecules from biological sources.     

Fe3O4 precipitation in magnetotactic bacteria

Using Mössbauer resonance spectroscopy of ⁵⁷Fe, we have determined the nature and distribution of major iron compounds in the magnetotactic bacterium Aquaspirillum magnetotacticum. In addition to magnetite (Fe₃O₄), cells contained a low-density hydrous ferric oxide, a high-density hydrous ferric oxide (ferrihydrite), and ferrous iron. Analysis at different temperatures of whole cells harvested early and late in growth, of mutant cells unable to synthesize magnetite, and of cell fractions enriched in ⁵⁷Fe indicated that Fe₃O₄ precipitation resulted from partial reduction of the high-density hydrous ferric oxide precursor.     

反复呼吸道感染儿童血清维生素A、维生素E水平与免疫球蛋白、T淋巴细胞亚群、NK细胞及骨密度的关系分析

摘要 目的：探讨反复呼吸道感染（RRTI）儿童血清维生素A、维生素E水平与免疫球蛋白（Ig）、T淋巴细胞亚群、NK细胞及骨密度的关系。方法：选择2018年2月至2020年12月我院儿科收治的107例RRTI患儿（感染组）和83例同期于我院体检的健康儿童（对照组）为研究对象,检测两组血清维生素A、维生素E水平、Ig水平,外周血T淋巴细胞亚群、NK细胞占比以及骨密度。分析维生素A、维生素E与Ig、T淋巴细胞亚群、NK细胞及骨密度的相关性。结果：感染组血清维生素A、维生素E、IgG、IgA、IgM及外周血CD3⁺T细胞百分比、CD4⁺T细胞百分比、CD3^-CD56⁺ NK细胞百分比、CD56brightNK细胞百分比、CD56dimNK细胞百分比、桡骨和胫骨骨密度均低于对照组（P＜0.05）,外周血CD8⁺T细胞百分比高于对照组（P＜0.05）。血清维生素A及维生素E水平与外周血CD8⁺T细胞百分比呈负相关（P＜0.05）,与IgG、IgA、IgM水平,外周血CD3⁺ T细胞百分比、CD4⁺T细胞百分比、CD3^-CD56⁺ NK细胞百分比、CD56brightNK细胞百分比、CD56dimNK细胞百分比、桡骨和胫骨骨密度呈正相关（P＜0.05）。结论：RRTI患儿血清维生素A、维生素E水平明显降低,且与免疫功能障碍和骨密度降低有关。     

Facile and greener hydrothermal honey-based synthesis of Fe3O 4/Au core/shell nanoparticles for drug delivery applications

In the present research, we report a greener, faster, and low-cost synthesis of gold-coated iron oxide nanoparticles (Fe₃O₄/Au-NPs) by different ratios (1:1, 2:1, and 3:1 molar ratio) of iron oxide and gold with natural honey (0.5% w/v) under hydrothermal conditions for 20 minutes. Honey was used as the reducing and stabilizing agent, respectively. The nanoparticles were characterized by X-ray diffraction (XRD), UV-visible spectroscopy, field emission scanning electron microscope (FESEM), energy-dispersive X-ray spectroscopy (EDXS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), vibrating sample magnetometer (VSM), and fourier transformed infrared spectroscopy (FT-IR). The XRD analysis indicated the presence of Fe₃O₄/Au-NPs, while the TEM images showed the formation of Fe₃O₄/Au-NPs with diameter range between 3.49 nm and 4.11 nm. The VSM study demonstrated that the magnetic properties were decreased in the Fe₃O₄/Au-NPs compared with the Fe₃O₄-NPs. The cytotoxicity threshold of Fe₃O₄/Au-NPs in the WEHI164 cells was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was demonstrated no significant toxicity in higher concentration up to 140.0 ppm which can become the main candidates for biological and biomedical applications, such as drug delivery.     

Comparative study of nano and bulk Fe3O4 induced oxidative stress in Wistar rats

Context: Magnetic nanomaterials (Fe₃O₄ NMs) have become novel tools with multiple biological and medical applications because of their biocompatibility. However, adverse health effects of these NMs are of great interest to learn.

Objective: This study was designed to assess the size and dose-dependent effects of Fe₃O₄ NMs and its bulk on oxidative stress biomarkers after post–subacute treatment in female Wistar rats.

Methods: Rats were daily administered with 30, 300 and 1000?mg/kg b.w. doses for 28?d of Fe₃O₄ NMs and its bulk for biodistribution and histopathological studies.

Results: Fe₃O₄ NMs treatment caused significant increase in lipid peroxidation levels of treated rats. It was also observed that the NM treatment elicited significant changes in enzyme activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in treated rat organs with major reduction in glutathione content. Metal content analysis revealed that tissue deposition of NM in the organs was higher when compared to bulk and caused histological changes in liver.

Conclusion: This study demonstrated that for same dose, NM showed higher bioaccumulation, oxidative stress and tissue damage than its bulk. The difference in toxic effect of Fe₃O₄ nano and bulk could be related to their altered physicochemical properties.