PVCL-MnO2纳米探针用于多形性胶质母细胞瘤的放疗增敏及MRI成像的实验研究

摘要 目的：探讨PVCL-MnO₂对多形性胶质母细胞瘤的放疗增敏作用,并进行体内MRI成像研究。方法：制备PVCL-MnO₂纳米探针,利用透射电子显微镜(Transmission Electron Microscope, TEM)对其形态进行表征,并使用Image J分析其尺寸分布。采用细胞增殖-毒性实验 (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT),测定PVCL-MnO₂协同放疗处理肿瘤细胞48 h后的细胞活性。将多形性胶质母瘤细胞瘤细胞进行PVCL-MnO₂共孵育后,协同放疗处理,分别使用免疫荧光,蛋白质印迹法等实验技术检测H2AX 组蛋白异型的磷酸化形式 (phosphorylated form of the histone protein H2AX, γ-H2AX),活性氧自由基(reactive oxygen species, ROS) 的产生及Bax,Bcl-2凋亡相关蛋白的表达。PVCL-MnO₂尾静脉注射至原位多形性胶质母细胞瘤小鼠中,在不同的时间点进行MRI扫描,观察成像效果。结果：PVCL-MnO₂颗粒粒径分布均匀,结构规整, 表现出良好的单分散性。PVCL-MnO₂联合放疗可有效增强DNA双链的断裂,ROS及促凋亡蛋白Bax的产生,同时下调了抗凋亡蛋白Bcl-2。MRI成像显示,PVCL-MnO₂具有较好的T1-加权MRI成像效果,在尾静脉注射PVCL-MnO₂ 后4 h,肿瘤部位的信号增强最明显, 随后信号开始下降。结论：PVCL-MnO₂可实现多形性胶质母细胞瘤的放疗增敏及MRI成像。     

巨噬细胞膜伪装纳米颗粒的制备和功能表征

摘要 目的：巨噬细胞具有炎症趋化能力,近年来巨噬细胞膜伪装的纳米递送载体引起研究者的广泛关注。本文提供了一种巨噬细胞膜伪装纳米颗粒的方法,即摄取-挤出法,并对该法制得的纳米颗粒进行表征,考察纳米颗粒在不同细胞中的摄取。方法：利用溶胶-凝胶法制备装载阿霉素的介孔硅（DMSN）纳米颗粒,再利用RAW 264.7巨噬细胞吞噬DMSN,最后将巨噬细胞连续挤出制得巨噬细胞膜伪装的载有阿霉素的介孔硅（DMSN@CM）纳米颗粒。动态光散射激光粒度仪（DLS）测定DMSN@CM颗粒的粒径和表面电位,透射电子显微镜（TEM）观察纳米颗粒形态,聚丙烯酰胺凝胶电泳（SDS-PAGE）验证细胞膜的成功伪装。然后通过激光共聚焦显微镜与流式细胞术共同考察了DMSN@CM在不同细胞中的摄取情况。结果：成功制备了DMSN和DMSN@CM纳米颗粒。DMSN粒径为116.7±3.2 nm,zeta表面电势为 -29.5± 1.3 mV;MSN@CM粒径为128.0±9.3 nm,zeta表面电势为 -26.7 ±1.2 mV。TEM与SDS-PAGE共同验证了DMSN@CM表面细胞膜的成功包覆。细胞摄取试验表明巨噬细胞膜的伪装可以抑制RAW 264.7细胞对DMSN@CM的摄取;促进MDA-MB-231细胞对DMSN@CM的摄取。结论：利用摄取-挤出法成功构建了DMSN@CM纳米颗粒,该法简便高效,为纳米颗粒的细胞膜伪装提供了一种新的手段。     

纳米铁氧化物对Pelotomaculum schinkii培养系丙酸厌氧降解产甲烷的影响

微生物能利用导电材料进行电子传递,提高种间电子传递效率。铁基纳米导电物质可以加速土壤及厌氧消化系统中微生物间的种间电子传递,促进有机废弃物的产甲烷过程。前期获得了厌氧丙酸富集培养系,互营丙酸氧化菌（Pelotomaculum schinkii）在培养系中占优势,本研究考察了10~4 000 mg/L 纳米铁氧化物对丙酸降解产甲烷过程的作用及微生物的影响。结果表明,低浓度的铁基纳米材料对丙酸降解有一定的促进作用,而高浓度会抑制产甲烷：10~1 000 mg/L纳米Fe₃O₄对产甲烷无明显影响,1 500~4 000 mg/L最大产甲烷速率抑制了26%~80%,延滞期增加了174%~222%;10~200 mg/L纳米Fe₂O₃使最大产甲烷速率提高了21%~29%,1 500~4 000 mg/L最大产甲烷速率抑制了48%~58%,延滞期增加了29%~85%。微生物群落解析结果表明,与对照相比,10~1 000 mg/L纳米Fe₂O₃使P. schinkii相对丰度略有增加,而4 000 mg/L纳米₃O₄/Fe₂O₃使P. schinkii的相对丰度下降了70.7%和55.9%,说明高浓度纳米铁氧化物会抑制P. schinkii的活性,导致丙酸降解及产甲烷速率降低。     

用于可视化光治疗的Mn3O4@CuS纳米粒的制备研究

摘要 目的：本研究旨在制备用于肿瘤可视化光治疗的多功能Mn₃O₄@CuS核壳型纳米粒,在磁共振成像的引导下,使用近红外光定点辐照,实现局部光热消融治疗。方法：（1）采用高温热解法制备油胺稳定的Mn₃O₄纳米粒,在其表面构建CuS壳层,并进行聚乙二醇修饰,得到分散于水相中的Mn₃O₄@CuS核壳型纳米粒。（2）通过透射电镜、紫外可见近红外吸收光谱等方法对该纳米粒进行理化性质表征,并研究其体外磁共振成像、光热升温等性能。结果：制备的水相分散的Mn₃O₄@CuS纳米粒,粒径均一且分散性较好,形态为近圆形,粒径为9.30±2.29 nm;紫外可见近红外吸收光谱图表明Mn₃O₄@CuS纳米粒在近红外区有较强吸收,最大吸收峰位于1100~1200 nm范围;磁共振成像分析结果可计算出Mn₃O₄@CuS纳米粒的纵向弛豫率r1为1.662 mM^-1s^-1,表明其具有较好的磁共振增强造影效果;光热升温曲线显示Mn₃O₄@CuS纳米粒可在785 nm近红外激光下升温至73.5 ℃,具备较好的光热治疗潜力。结论：本文成功制备出水相分散的Mn₃O₄@CuS核壳型纳米粒,具有良好的磁共振造影成像性能和光热升温效应,有望应用于磁共振成像引导下的肿瘤可视化光治疗。     

DCE-MRI联合DWI对直肠癌患者术前T、N分期及系膜淋巴结良恶性的诊断价值

摘要 目的：探讨动态对比增强磁共振(DCE-MRI)联合弥散加权成像（DWI）诊断直肠癌术前T、N分期和系膜淋巴结良恶性的价值。方法：收集2017年2月至2019年10月中国医科大学附属本溪中心医院和中国医科大学附属盛京医院接诊的80例直肠癌患者,均进行常规核磁共振成像（MRI）、DCE-MRI、DWI扫描,获得DCE-MRI、DWI定量参数[转运常数（K ^trans ）、细胞外血管外空间的体积分数（V _e ）、速率常数（K _ep ）、表观扩散系数(ADC)],比较不同T、N分期、不同性质系膜淋巴结DCE-MRI、DWI参数,及其对T、N分期和系膜淋巴结性质的诊断效能。结果：直肠癌癌灶K ^trans 、 K _ep 、V _e 高于正常肠壁,ADC低于正常肠壁（P＜0.05）。TNM分期为T_Ⅲ～Ⅳ期的患者K ^trans 、 K _ep 、V _e 高于T_Ⅰ～Ⅱ期,ADC低于T_Ⅰ～Ⅱ期（P＜0.05）;TNM分期为N₁期的患者K ^trans 、K _ep 、V _e 高于N₀期,ADC低于N₀期（P＜0.05）。联合诊断的灵敏度、特异度、阳性预测值、阴性预测值较高。结论：DCE-MRI联合DWI对直肠癌术前T、N分期、系膜淋巴结性质诊断价值较高。     

聚乙二醇连接荧光Cy5.5构建超小超顺磁性氧化铁成像探针的制备与表征

摘要 目的：以超小超顺磁性氧化铁颗粒为载体通过聚乙二醇连接荧光Cy5.5构建核磁/荧光分子探针并表征。方法：取Cy5.5-NHS荧光粉末溶于二甲基甲砜（Dimethyl sulfoxide,DMSO）溶液,将PEG四氧化三铁颗粒离心超滤之后用磷酸盐缓冲液（Phosphate Buffered Saline,PBS）重悬纳米颗粒改变PEG化四氧化三铁纳米颗粒溶液pH。将配置好的Cy5.5荧光加入到四氧化三铁颗粒中,恒温摇床孵育,通过离心过滤器去除较大铁离子与未结合的荧光,静置后检测水合粒径及Zeta电位,纽麦小核磁检测其驰豫率,CCK-8实验检测其细胞毒性,激光共聚焦显微镜观察探针被细胞摄取情况。结果：合成Cy5.5-PEG-FeO₄探针,透射电镜（Transmission electron microscope,TEM）显示探针粒径为16.8±2.4nm,纳米颗粒的水合径为43.4±17.6 nm,Zeta电位为-18.0 mV。驰豫率为39.5 mM^-1?s^-1,R²为0.98。细胞毒性实验结果显示对细胞有轻微毒性,且毒性与浓度呈依赖性。激光共聚焦结果显示此款探针可顺利被细胞摄取。结论：成功合成Cy5.5-PEG-FeO₄探针。     

目标导向液体管理策略对腹腔镜卵巢癌根治术患者血流动力学、组织灌注指标及炎性细胞因子水平的影响

摘要 目的：探讨目标导向液体管理策略对腹腔镜卵巢癌根治术患者血流动力学、组织灌注指标及炎性细胞因子水平的影响。方法：选择2018年2月至2020年8月我院收治的126例拟行腹腔镜卵巢癌根治手术患者,随机分为两组。对照组（63例）采用传统液体管理,观察组（63例）采用目标导向液体管理策略。比较两组手术时间、术中失血量、输液量、尿量、术后住院时间、使用血管活性药物比例差异,以及血流动力学指标[平均动脉压（MAP）、中心静脉压（CVP）、心输出量（CO）,每搏量指数（SVI）、每搏输出量变异度（SVV）、体外循环阻力（SVR）,心脏指数（CI）]、组织灌注指标[中心性静脉血氧饱和度（ScvO₂）、动脉血乳酸（aLac）、中心静脉-动脉血二氧化碳分压差(Pcv-aCO₂)、氧摄取率估计值（O₂ERe)、氧供指数(DO₂I)]、血清炎性细胞因子[白介素-6（IL-6）、白介素-10（IL-10）、白介素-1β（IL-1β）、高迁移率族蛋白B1（HMGB1）]水平差异。结果：观察组术中失血量、输液量、尿量、术后住院时间均低于对照组（P＜0.05）,使用血管活性药物比例高于对照组（P＜0.05）。观察组建立气腹后30 min（T₂）、手术结束时(T₃)、苏醒时(T₄)MAP、CVP、CO、SVI、CI、SVV、O₂ERe、DO₂I高于对照组（P＜0.05）,aLac低于对照组（P＜0.05）。观察组气管插管后5 min（T₁）、T₂、T₃、T_{<4/sub>血清IL-6、IL-10、HMGB1、IL-1β水平均低于对照组（P＜0.05）。结论：目标导向液体管理策略更有助于维持腹腔镜卵巢癌根治术患者围术期血流动力学稳定,并保证组织恰当充分灌注,降低血清炎性细胞因子水平。}     

艾司氯胺酮联合舒芬太尼对剖宫产围手术期镇痛、应激指标及抑郁评分的影响

摘要 目的：探究艾司氯胺酮联合舒芬太尼对剖宫产围手术期镇痛、应激指标及抑郁评分的影响。方法：选取2021年1月~2021年10月期间我院收治的行剖宫产手术的180例产妇,采用随机数字表法分为A组、B组、C组各60例。A组胎儿娩出后即刻静脉输注艾司氯胺酮,术后艾司氯胺酮联合舒芬太尼静脉自控镇痛;B组和C组胎儿娩出后不给予艾司氯胺酮,用生理盐水代替;B组术后静脉自控镇痛与A组相同,C组术后给予舒芬太尼静脉自控镇痛。比较三组产妇术后4 h（T₁）、8 h（T₂）、12 h（T₃）、24 h（T₄）、48 h（T₅）疼痛程度[简化McGill疼痛问卷（SF-MPQ）评分]、镇静程度（Ramsay镇静评分）,记录三组术前1 d和术后1 d的应激指标[去甲肾上腺素（NE）、皮质醇（Cor）、促肾上腺皮质激素（ACTH）]水平,比较三组术前1 d和术后3、7 d抑郁程度[爱丁堡产后抑郁量表（EPDS）],比较三组不良反应发生情况。结果：T₁、T₂、T₃时A组视觉模拟评分（VAS）明显低于B、C组（P均<0.05）,T₁、T₂时A组痛分级指数（PRI）感觉分明显低于B、C组（P均<0.05）,T₁、T₂、T₃、T₄、T₅时A组PRI情感分明显低于B、C组（P均<0.05）,T₁时A组现时疼痛强度（PPI）评分明显低于B、C组（P均<0.05）。T₁、T₂、T₃、T₄、T₅时,三组Ramsay镇静评分比较差异均无统计学意义（P均>0.05）。术后1 d,三组NE、Cor、ACTH水平均较术前1 d显著升高（P均<0.05）,术前1 d和术后1 d,三组NE、Cor、ACTH水平比较差异均无统计学意义（P均>0.05）;术后3、7 d时A组EPDS评分明显低于术前1 d和同时间B、C组（P均<0.05）;三组不良反应发生情况对比无显著性差异（P均>0.05）。结论：艾司氯胺酮联合舒芬太尼在剖宫产围术期镇痛中应用效果良好,能够减轻产妇术后早期抑郁程度。     

对比分析丙泊酚/依托咪酯混合液分别联合艾司氯胺酮、盐酸舒芬太尼在无痛胃肠镜检查中的应用

摘要 目的：探讨对比分析丙泊酚/依托咪酯混合液分别联合艾司氯胺酮、盐酸舒芬太尼在无痛胃肠镜检查中的应用效果。方法：选取我院2022年1月到2022年12月收治的80例行无痛胃肠镜检查患者作为研究对象,应用随机数字表法将所有患者分为观察组与对照组,每组40例。对照组患者应用丙泊酚/依托咪酯混合液+盐酸舒芬太尼进行静脉麻醉,观察组应用丙泊酚/依托咪酯混合液+艾司氯胺酮进行静脉麻醉,对比两组患者入室时基础值（T₁）、开始镇静时（T₂）、胃镜置入后（T₃）、肠镜置入后（T₄）、操作结束即刻（T₅）五个不同时间血流动力学指标变化,并对比患者麻醉起效时间、麻醉药追加次数、追加麻醉药总量、意识恢复时间、PACU停留时间,对比检查不同时间认知功能情况以及不良反应发生率。结果：两组患者T₁时间舒张压（SBP）、收缩压（DBP）、平均动脉压（MAP）、心率（HR）对比无明显差异（P＞0.05）,观察组患者同组间T₁、T₂、T₃、T₄、T₅时间SBP、DBP、MAP、HR对比无明显差异（P＞0.05）,对照组T₁到T₂时间SBP、DBP、MAP、HR水平降低,到T₃和T₄时间升高,T₅时间恢复平稳,且观察组与对照组相比T₂、T₃、T₄时间SBP、DBP、MAP水平对比差异显著,观察组低于对照组,T₃时间观察组HR低于对照组（P＜0.05）;观察组麻醉起效时间、麻醉药追加次数、追加麻醉药总量、意识恢复时间、PACU停留时间显低于对照组（P＜0.05）;两组患者检查后6 h S100B 蛋白明显升高,检查后1 d的S100B 蛋白逐渐降低,且观察组低于对照组,检查后6 h褪黑素明显降低,检查后1 d的褪黑素逐渐升高,观察组高于对照组（P＜0.05）;观察组患者不良反应发生率明显低于对照组（P＜0.05）。结论：丙泊酚/依托咪酯混合液联合艾司氯胺酮与丙泊酚/依托咪酯混合液联合盐酸舒芬太尼对于无痛胃肠镜检查麻醉效果显著,能够改善患者血流动力学指标波动,减少麻醉药追加次数,且麻醉起效快,苏醒质量好,另外能够进一步改善患者检查后认知功能情况,安全性较高。     

老年慢性心力衰竭患者甲状腺激素水平与认知功能、心功能及心血管事件的关系研究

摘要 目的：探讨老年慢性心力衰竭（CHF）患者甲状腺激素（TH）水平与认知功能、心功能及心血管事件的关系。方法：将我院2018年6月～2020年6月收治的140例老年CHF患者纳入研究,检测患者TH指标[血清三碘甲状腺原氨酸（T₃）、游离三碘甲状腺原氨酸（FT₃）、甲状腺素（T₄）、游离甲状腺素（FT₄）、促甲状腺激素（TSH）]水平。按蒙特利尔认知评估量表（MoCA）评分将患者分为认知障碍组（MoCA评分＜26分）、非认知障碍组（MoCA评分≥26分）,比较两组各TH指标与MoCA评分。比较不同纽约心脏病协会（NYHA）分级患者的TH指标与心功能指标[左室射血分数（LVEF）、左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）]。根据患者住院期间是否发生心血管事件分为心血管事件组和非心血管事件组,比较两组各TH指标。经Pearson线性相关分析TH指标与MoCA评分、心功能指标的相关性。结果：认知障碍组血清T₃、FT₃水平及MoCA评分较非认知障碍组明显降低（P＜0.05）。Ⅲ级、Ⅳ级组的血清T₃、FT₃水平及LVEF较Ⅰ级、Ⅱ级组显著降低,其中Ⅳ级组低于Ⅲ级组（P＜0.05）。Ⅲ级、Ⅳ级组的LVEDD、LVESD较Ⅰ级、Ⅱ级组明显升高,且Ⅳ级组高于Ⅲ级组（P＜0.05）。心血管事件组血清T₃、FT₃水平较非心血管事件组显著降低（P＜0.05）。Pearson线性相关分析显示：血清T₃、FT₃水平与MoCA评分、LVEF呈正相关（均P＜0.05）,与LVEDD、LVESD呈负相关（均P＜0.05）。结论：老年CHF患者血清T₃、FT₃水平下调与其认知功能、心功能降低及心血管事件的发生密切相关,通过检测其血清T₃、FT₃水平,有利于进一步了解其病情变化。     

A possible theranostic approach of chitosan-coated iron oxide nanoparticles against human colorectal carcinoma (HCT-116) cell line

Iron oxides have become increasingly popular for their use as a diagnostic and therapeutic tool in oncology. This study aimed to improve pharmacological valuable of Fe₃O₄, which may be use to diagnosis colorectal cancers (CRC). Here, we have developed chitosan (CS) coated Fe₃O₄ through a cost-effective procedure. First, we determined the characterization of OA-C-Fe₃O₄ by FTIR, UV–Vis spectra, and TEM. Then, we evaluated the photodynamic therapeutic (PDT) activity of OA-C-Fe₃O₄ in human colorectal carcinoma cell lines (HCT 116). Current results revealed that the light-induced enhanced reactive oxygen species (ROS) activity of the nanoparticles (NPs) and caused cell death via the activity of caspase 9/3. The in vitro magnetic resonance imaging (MRI) experiments in (HCT 116) and human embryonic kidney cells (HEK 293) illustrated that nanohybrid is an effective MRI contrasting agents for the diagnosis of colorectal cancer.     

Fe3O4-PEG-CD56/Avastin@Ce6纳米探针的合成及细胞MR成像初步研究

目的:探讨Fe_3O_4-PEG-CD56/Avastin@Ce6靶向探针与NK92细胞的结合能力并进行细胞体外MRI成像。方法:制备Fe_3O_4-PEG-CD56/Avastin@Ce6纳米探针,对合成的材料进行表征。应用凋亡试剂盒测定不同浓度的材料对NK92的细胞毒性,通过流式细胞术分析纳米材料与NK92细胞的结合能力和应用MRI对细胞进行体外成像并分析其T2信号强度的改变。结果:合成的纳米探针具有较好的生物相容性,且对NK92细胞的影响较小,不同浓度下细胞凋亡水平基本一致,与NK92细胞结合的材料随浓度的增加而逐渐增加。MRI检查提示不同浓度探针孵育的NK92细胞T2加权像(T2WI)的信号均降低。结论:Fe_3O_4-PEG-CD56/Avastin@Ce6探针对NK92细胞具有靶向性,3.0 T MR扫描仪可对其进行体外监测。     

In vitro spectroscopic investigation of groove binding interaction of Fe3O4@CaAl-LDH@L-Dopa with calf thymus DNA

Abstract

The principal goal of this study is to evaluate the interaction of Fe₃O₄@CaAl-LDH@L-Dopa and Fe₃O₄@CaAl-LDH nanoparticles with calf thymus DNA. The magnetic nanoparticles were previously prepared by a chemical co-precipitation method, and the surface of the Fe₃O₄ nanoparticles was coated with CaAl layered double hydroxides. The antiparkinsonian drug “L-Dopa” was carried by this core–shell nanostructure to achieve the drug delivery system with suitable properties for biological applications. Also, the interaction of Fe₃O₄@CaAl-LDH@L-Dopa and Fe₃O₄@CaAl-LDH nanoparticles with CT-DNA was studied using, UV–Visible spectroscopy, viscosity, circular dichroism (CD), and fluorescence spectroscopy techniques. The results of investigations demonstrated that Fe₃O₄@CaAl-LDH@L-Dopa and Fe₃O₄@CaAl-LDH nanoparticles have interacted via minor groove binding and intercalated to CT-DNA, respectively.     

In vitro cytotoxicity screening of water-dispersible metal oxide nanoparticles in human cell lines

In this study, we present in vitro cytotoxicity of iron oxide (Fe₃O₄) and manganese oxide (MnO) using live/dead cell assay, lactate dehydrogenase assay, and reactive oxygen species detection with variation of the concentration of nanoparticles (5–500 μg/ml), incubation time (18–96 h), and different human cell lines (lung adenocarcinoma, breast cancer cells, and glioblastoma cells). The surface of nanoparticles is modified with polyethyleneglycol-derivatized phospholipid to enhance the biocompatibility, water-solubility, and stability under an aqueous media. While the cytotoxic effect was negligible for 18 h incubation even at highest concentration of 500 μg/ml, MnO nanoparticle represented higher level of toxicity than those of Fe₃O₄ and the commercial medical contrast reagent, Feridex after 2 and 4 day incubation time. However, the cytotoxicity of Fe₃O₄ is equivalent or better than Feridex based on the live/dead cell viability assay. The engineered MnO and Fe₃O₄ exhibited excellent stability compared with Feridex for a prolonged incubation time.     

Cytotoxicity,permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells

Wide applications and extreme potential of metal oxide nanoparticles (NPs) increase occupational and public exposure and may yield extraordinary hazards for human health. Exposure to NPs has a risk for dysfunction of the vascular endothelial cells. The objective of this study was to assess the cytotoxicity of six metal oxide NPs to human cardiac microvascular endothelial cells (HCMECs) in vitro. Metal oxide NPs used in this study included zinc oxide (ZnO), iron(III) oxide (Fe₂O₃), iron(II,III) oxide (Fe₃O₄), magnesium oxide (MgO), aluminum oxide (Al₂O₃), and copper(II) oxide (CuO). The cell viability, membrane leakage of lactate dehydrogenase, intracellular reactive oxygen species, permeability of plasma membrane, and expression of inflammatory markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, macrophage cationic peptide-1, and interleukin-8 in HCMECs were assessed under controlled and exposed conditions (12–24 h and 0.001–100 μg/ml of exposure). The results indicated that Fe₂O₃, Fe₃O₄, and Al₂O₃ NPs did not have significant effects on cytotoxicity, permeability, and inflammation response in HCMECs at any of the concentrations tested. ZnO, CuO, and MgO NPs produced the cytotoxicity at the concentration-dependent and time-dependent manner, and elicited the permeability and inflammation response in HCMECs. These results demonstrated that cytotoxicity, permeability, and inflammation in vascular endothelial cells following exposure to metal oxide nanoparticles depended on particle composition, concentration, and exposure time.     

Evaluation of microbubbles as contrast agents for ultrasonography and magnetic resonance imaging

Background

Microbubbles (MBs) can serve as an ultrasound contrast agent, and has the potential for magnetic resonance imaging (MRI). Due to the relatively low effect of MBs on MRI, it is necessary to develop new MBs that are more suitable for MRI. In this study, we evaluate the properties of SonoVue® and custom-made Fe₃O₄-nanoparticle-embedded microbubbles (Fe₃O₄-MBs) in terms of contrast agents for ultrsonography (US) and MRI.

Methodology/Principal Findings

A total of 20 HepG2 subcutaneous-tumor-bearing nude mice were randomly assigned to 2 groups (i.e., n = 10 mice each group), one for US test and the other for MRI test. Within each group, two tests were performed for each mouse. The contrast agent for the first test is SonoVue®, and the second is Fe₃O₄-MBs. US was performed using a Technos^MPX US system (Esaote, Italy) with a contrast-tuned imaging (CnTI™) mode. MRI was performed using a 7.0T Micro-MRI (PharmaScan, Bruker Biospin GmbH, Germany) with an EPI-T₂* sequence. The data of signal-to-noise ratio (SNR) from the region-of-interest of each US and MR image was calculated by ImageJ (National Institute of Health, USA). In group 1, enhancement of SonoVue® was significantly higher than Fe₃O₄-MBs on US (P<0.001). In group 2, negative enhancement of Fe₃O₄-MBs was significantly higher than SonoVue® on MRI (P<0.001). The time to peak showed no significant differences between US and MRI, both of which used the same MBs (P>0.05). The SNR analysis of the enhancement process reveals a strong negative correlation in both cases (i.e., SonoVue® r = −0.733, Fe₃O₄-MBs r = −0.903, with P<0.05).

Conclusions

It might be important to change the Fe₃O₄-MBs'' shell structure and/or the imagining strategy of US to improve the imaging quality of Fe₃O₄-MBs on US. As an intriguing prospect that can be detected by US and MRI, MBs are worthy of further study.     

Optimization of the covalent coupling and ionic adsorption of magnetic nanoparticles on Flavobacterium ATCC 27551 using the Taguchi method

Abstract

Flavobacterium ATCC 27551 was used as a model system for the preparation of magnetic biocatalysts. The magnetic modification was carried out by covalently binding carboxylate- and amino-modified magnetic nanoparticles onto cells. Magnetic Fe₃O₄ nanoparticles were also used for ionic adsorption on the cell surface. Magnetically modified cells were concentrated using a magnet and exhibited organophosphate hydrolyzing activity. The Taguchi method was used to optimize the binding of the magnetic nanoparticles on the cell surface. SEM image analyses demonstrated good linkage of the magnetic nanoparticles over the Flavobacterium ATCC 27551 cell surface. Under optimal conditions, the magnetic cells displayed specific activity ratios of 93%, 89% and 95%, compared with untreated cells, after the covalent coupling with carboxylate- and amino-modified magnetic nanoparticles and the ionic adsorption of magnetic Fe₃O₄ nanoparticles, respectively.     

Properties Evaluation of a New MRI Contrast Agent Based on Gd-Loaded Nanoparticles

Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The aim of this research was to characterize a novel emulsion composed of a silicon-based nanocomposite polymer (NCP) and gadolinium (III) oxide (Gd₂O₃) nanoparticles. The size and morphological structure of this nanoparticle are determined by particle size analysis device (zeta sizer) and transmission electronic microscope. We determined composition of Gd₂O₃ nanoparticles with energy dispersive X-ray analysis (EDXA) and magnetic resonance signal by T ₁-weighted MRI. Cytotoxicity of Gd₂O₃ nanoparticles in SK-MEL-3 cancer cells was evaluated. Zeta sizer showed Gd₂O₃ nanoparticles to be 75 nm in size. EDXA indicated the two main chemical components of gadolinium-nanocomposite polymer emulsion: gadolinium and silicon and MRI also showed a significantly higher incremental relaxivity for Gd₂O₃ nanoparticles compared to Magnevist (conventional contrast agent). In such concentrations, the slope of R₁ relaxivity (1/T ₁) vs. concentration curve of Magnevist and Gd₂O₃ were 4.33, 7.98 s⁻¹ mM⁻¹. The slope of R₂ relaxivity (1/T ₂) vs. concentration curve of Magnevist and Gd₂O₃ were 5.06, 13.75 s⁻¹ mM⁻¹. No appreciable toxicity was observed with Gd₂O₃ nanoparticles. Gadolinium-nanocomposite polymer emulsion is well characterized and has potential as a useful contrast agent for magnetic resonance molecular imaging.     

DNA binding and cytotoxicity studies of magnetic nanofluid containing antiviral drug oseltamivir

In this work, the possibility of preparing a nanoparticle with improved treatment properties was investigated. In this regard, synthesis, characterization, in vitro cytotoxicity and DNA binding of Fe₃O₄@oleate/oseltamivir magnetic nanoparticles (MNPs) were investigated. Fe₃O₄ nanoparticles were synthesized via chemical co-precipitation and coated by oleate bilayers. Then, Fe₃O₄@OA MNPs were functionalized with an antiviral drug (oseltamivir), for better biological applications. The MNPs were subsequently characterized by zeta sizer and Zeta potential measurements, Fourier transform infrared (FT-IR) spectroscopy, vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) analyses. The TEM image demonstrated that average sizes of Fe₃O₄@OA/oseltamivir MNPs were about 8?nm. The in vitro cytotoxicity of Fe₃O₄@OA/oseltamivir MNPs was studied against cancer cell lines (MCF-7 and MDA-MB-231) and compared with oseltamivir drug. The results illustrated that Fe₃O₄@OA/oseltamivir magnetic nanoparticles have better antiproliferative effects on the mentioned cell lines as compared with oseltamivir. Also, in vitro DNA binding studies were done by UV–Vis, circular dichroism, and Fluorescence spectroscopy. The results indicated that Fe₃O₄@OA/oseltamivir MNPs bound to DNA via groove binding. Moreover, this magnetic nanofluid has potential for magnetic hyperthermia therapy due to magnetic core of its nanoparticles.

Communicated by Ramaswamy H. Sarma     

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.