磁靶向药物的磁场定位分析

本研究介绍毛细管内磁性微粒（Fe2O3）的磁场定位实验，对磁性颗粒在毛细血管内的受力进行分析，得到了磁靶向药物的磁场定位条件。分析了药物载体直径及所包覆药物层厚度对定位所需最小磁场梯度的影响，以通电螺线管磁场为例探讨了病变部位离体表不同深度时定位治疗的方法，结果可供磁性载体设计和磁靶向药物定位治疗参考。     

5-氟尿嘧啶磁性纳米粒的制备及性能

背景:磁性载药微粒在外加磁场作用下,能实现定向治疗作用,减少全身毒副作用,同时作为缓释载体,能减少药物的频繁给药,达到有效治疗目的。目的:制备5-氟尿嘧啶的磁性纳米粒,评价微球性能。方法:以海藻酸钠和壳聚糖作为壁材,5-氟尿嘧啶为模型药物,Span80为乳化剂,液体石蜡为分散介质,乳化-复凝聚法制备磁性纳米粒。并从外观、稳定性、磁响应性、结构、溶胀实验及体外释放实验等多方面考察纳米粒性能。结果与结论:所制5-氟尿嘧啶的磁性纳米粒形态良好,均匀圆整,分散性较好,粒径在100~300nm,具有较好稳定性和磁响应性。考察Fe3O4用量的影响,发现随着Fe3O4用量的增加,磁响应性增强,但载药量下降。红外谱图说明微粒中包裹磁性物质Fe3O4,及5-氟尿嘧啶与壁材之间产生相互作用。将5-氟尿嘧啶磁性纳米粒分别浸渍在蒸馏水,0.9%NaCl溶液和磷酸盐缓冲液(pH=7.4)中,结果蒸馏水吸水速度最快且溶胀率最大,磷酸盐缓冲液(pH=7.4)吸水程度最小且溶胀率最小。微粒的缓释性能良好,50h内释放的药物占总含药量的53.20%。     

膀胱癌经尿道电切除术后吡柔比星膀胱灌注预防复发的临床观察

目的探讨膀胱灌注吡柔比星（THP）预防浅表性膀胱癌术后复发的安全性及疗效。方法对83例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术（TURBT）,术日及术后1周开始用THP（30mg／40m1）进行膀胱内定期灌注,每次药物在膀胱内保留30～60min,每周1次,连续8次,以后每月1次,连续10次,并随访18～45个月。结果83例患者均未见明显全身性药物不良反应,仅15例出现轻微膀胱刺激症状。结论膀胱灌注THP预防浅表性膀胱癌术后复发的疗效确切,不良反应小,安全性好,是较理想的膀胱灌注化疗药物。     

纳米磁性阿霉素人血白蛋白微球的制备与表征

目的：制备用于肿瘤靶向治疗的纳米Fe3O4磁性粒子和磁性阿霉素靶向抗癌微球。方法：采用液相共沉淀法制备纳米Fe3O4颗粒，采用XRD、HRTEM等测试手段埘该纳米粉进行表征；随后制备磁性阿霉素白蛋白微球，利用HRTEM对其包裹性能进行表征，同时采用荧光光谱法对其载药量进行测试。结果：纳米Fe，O。磁性粒子的平均粒径为16．3nm，分布宽度为5．8nm；磁性阿霉素微球的有效载药量为2．65％、表观载药量为3．Ol％。结论：该研究为肿瘤的药物化疗提供了一种新型的方法和材料，即磁件靶向微球定向治疗肿瘤的方法。     

叶酸分子靶向载顺铂磁性纳米药物制备及表征

背景：醛基化海藻酸钠具有良好的水溶性和组织相容性,利用其改性Fe3O4磁性纳米颗粒可增加表面活性和稳定性,叶酸的修饰可赋予载体分子靶向性。 目的：制备具有叶酸受体靶向及磁靶向的载顺铂磁性纳米药物(CDDP-FA-ASA-MNPs)。 方法：采用高碘酸钠氧化法制备醛基化海藻酸钠,叶酸的羧基经二环己基碳二亚胺和N-羟基琥珀酰亚胺活化后合成FA与双端氨基聚乙二醇的耦连产物FA-PEG,化学共沉淀法制备Fe3O4,海藻酸钠侧链含有大量羧基,85 ℃下与Fe3O4纳米颗粒表面的羟基形成化学键结合,然后通过雪夫氏碱将FA-PEG与醛基化海藻酸钠相连接,最后根据配位络合的原理,顺铂分子中的-Cl被海藻酸钠的羧基取代,形成稳定的叶酸和醛基化海藻酸钠改性载顺铂磁性纳米复合物。 结果与结论：所制备的磁性纳米药物呈颗粒状,稳定分散于水溶液中,Fe3O4磁核平均粒径为(8.116±0.24) nm,流体力学直径为(110.9±1.7) nm,zeta电位为(-26.45±1.26) mV,最大饱和磁化强度为56.2 emu/g,顺铂包封率为(49.05±1.58)%,载药量为(14.31±0.49)%。体外实验证实,叶酸分子靶向载顺铂磁性纳米药物能被叶酸受体表达阳性的鼻咽癌细胞HNE-1和喉癌细胞Hep-2选择性摄取,而叶酸受体表达阴性的鼻咽癌细胞CNE-2则不摄取。提示所制备的CDDP-FA-ASA-MNPs具有良好的水溶性和稳定性,能被叶酸受体表达阳性的鼻咽癌和喉癌细胞摄取。     

聚乙二醇-聚乙烯亚胺/四氧化三铁纳米磁流体的毒性及其生物相容性

背景:为实现纳米基因药物在治疗肿瘤中实现高靶向性,课题采用聚乙二醇和聚乙烯亚胺修饰的磁性四氧化三铁纳米粒(PEG-PEI/Fe3O4)作为基因药物载体,在提高载体载药能力的同时,使载体具有超顺磁性,增加药物靶向性能。目的:评价PEG-PEI/Fe3O4纳米磁流体体外和体内毒性。方法:对制备的PEG-PEI/Fe3O4纳米磁流体进行表征达到纳米材料水平后,过滤稀释5～20倍培养7702细胞和HpG2细胞,进行体外MTT毒性试验;通过体内溶血试验和微核试验测定生物相容性和体内毒性。结果与结论:MTT结果显示,PEG-PEI/Fe3O4纳米磁流体对7702细胞毒性0～1级,对正常肝细胞无害;PEG-PEI/Fe3O4纳米磁流体对HpG2细胞有轻微的旁观者抑制效应;PEG-PEI/Fe3O4纳米磁流体溶血率为0.372%,远小于5%;微核试验结果表明PEG-PEI/Fe3O4纳米磁流体无致畸、致突变作用。     

吡柔比星膀胱灌注预防浅表性膀胱癌术后复发的疗效观察

目的探讨吡柔比星（THP）膀胱内灌注预防浅表性膀胱癌术后复发的效果。方法患者随机分成两组,一组患者膀胱灌注卡介苗（BCG）（40例）,另一组膀胱灌注THP（40例）,随访6～24个月,观察两组复发情况及不良反应。结果BCG组和THP组2年复发率分别为12．5％（5／40）、14．0％（6／43）;两组间比较差异无统计学意义（x^2=0．038,P〉0．05）,而THP组不良反应发生率明显低于BCG组（x^2=9．565,P〈0．01）。结论膀胱灌注THP预防浅表性膀胱癌术后复发的疗效确切,不良反应小,安全性好。     

吡柔比星与羟基喜树碱膀胱灌注预防表浅性膀胱癌术后复发的疗效对比

目的：对比分析吡柔比星（ THP)与羟基喜树碱（ HCPT)膀胱灌注预防表浅性膀胱癌术后复发的效果。方法选择2010年12月—2011年12月蚌埠医学院第一附属医院收治的80例表浅性膀胱癌术后患者,按数字表法随机分为两组,各40例,分别采用THP （ THP组)和HCPT（ HCPT组)予以膀胱灌注治疗。观察并比较两组治疗后3、6、12、24个月膀胱癌的复发情况以及不良反应发生情况。结果所有患者均随访24个月。 THP组复发率15．0%（6/40),HCPT组复发率17．5%（7/40),差异无统计学意义（χ2=0．092, P>0．05)。 THP组不良反应发生率27．5%（11/40),HCPT组不良反应发生率17．5%（7/40),两组差异无统计学意义（χ2=1．147, P>0．05)。结论 THP与HCPT膀胱灌注用于预防表浅性膀胱癌术后复发的疗效相似且不良反应较轻,耐受性好,均可作为一线药物用于临床膀胱灌注治疗。     

静磁场靶向药物递送系统在肿瘤诊疗中的研究进展

化疗是治疗肿瘤的传统手段之一,但其具有组织非特异性,在抑制肿瘤细胞生长的同时也会对正常细胞产生毒副作用.磁靶向药物递送系统可通过具有生物相容性的、稳定的磁性纳米颗粒载体将抗癌药物在外磁场的引导下,靶向运输和浓聚在肿瘤组织.该技术不仅提高了药物运输的效率和药物的抗癌活性,还能降低药物用量和减轻毒副作用.载药磁性纳米颗粒和所应用的外磁场的性质是影响磁性纳米颗粒靶向肿瘤组织的重要影响因素.载药磁性纳米颗粒的靶向递送是否有效,主要依赖靶向目标位置处所应用的磁场和磁场强度是否足够吸引束缚载药磁性纳米颗粒在肿瘤组织中停留以及释放.对静磁场在引导磁性纳米颗粒靶向肿瘤组织研究的新进展进行综述,为静磁场在靶向肿瘤治疗方面提供一定的科研基础支持.     

旋转磁场中加导磁材料后其磁场分布研究

目的:根据靶向治疗的原理,利用外加磁场引导磁性药物至肿瘤部位并滞留,分析在靶部位处外加导磁材料后磁场的分布。方法:建立纳米铁受力的物理模型。用ANSYS软件进行了磁场分布的模拟。结果:导磁材料附近磁场强度明显增强,并且与周围组织的磁场强度差别很大,纳米铁可以高效的聚积于此处。结论:旋转磁场及导磁材料有助于放射性纳米铁核素在肿瘤部位的聚集,减少体内其它部位的残留,提高靶向治疗的效果。为今后的研究奠定了基础。     

载磁性氧化铁CA-PLGA纳米颗粒对宫颈癌细胞的影响

目的 研究纳米四氧化三铁(Fe3O4)颗粒包裹不同外壳材料对宫颈癌细胞HeLa毒性的影响.方法 通过无溶剂热分解法制备磁性纳米Fe3O4颗粒并分别使用聚乳酸-羟基乙酸共聚物(PLGA)和胆酸(CA)修饰的PLGA(CA-PLGA)星型共聚物包裹,对其进行验证表征后,使用激光共聚焦显微镜观察HeLa细胞对纳米颗粒的摄取,并用噻唑蓝(MTT)法测定上述两种材料包裹的纳米Fe3O4颗粒对HeLa细胞的毒性作用.结果 制备的单个纳米Fe3O4颗粒粒径约7 nm,载Fe3O4的PLGA和CA-PLGA纳米颗粒均呈球状,粒径约200 nm,理论载药量为10％.当Fe3O4纳米颗粒的质量浓度相同(25 μg/ml)时,载Fe3O4的CA-PLGA纳米颗粒对HeLa细胞的毒性小于对应的PLGA纳米颗粒.结论 CA-PLGA星型共聚物可降低磁性纳米Fe3O4颗粒的细胞毒性,在生物体内具有广阔的应用前景.     

Multifunctional polyglycerol-grafted Fe₃O₄@SiO₂ nanoparticles for targeting ovarian cancer cells

Ligand-mediated magnetic resonance (MR) contrast agents would be highly desirable for cancer diagnosis. In the present study, nanoparticles of Fe?O? core with fluorescent SiO? shell were synthesized and grafted with hyperbranched polyglycerol (HPG-grafted Fe?O?@SiO? nanoparticles). These nanoparticles have a hydrodynamic diameter of 47.0 ± 4.0 nm, and are very stable in aqueous solution as well as in cell culture medium. Numerous surface hydroxyl groups of these nanoparticles were conjugated with folic acid by a thiol 'click' reaction. The successful covalent attachment of folic acid on the nanoparticles was confirmed by FTIR and XPS analyses. Both MR imaging and fluorescence microscopy show significant preferential uptake of the folic acid-conjugated polyglycerol-grafted Fe?O?@SiO? (FA-HPG-grafted Fe?O?@SiO?) nanoparticles by human ovarian carcinoma cells (SKOV-3) as compared to macrophages and fibroblasts. Such nanoparticles can potentially be used to provide real-time imaging in ovarian cancer resection.     

The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance

Although much effort has been extended to the efficient cancer therapies, the drug resistance is still a major obstacle in cancer chemotherapeutic treatments. Almost 90% of the cancer therapy failure is caused by the relative problems. Recently, the application of drug coated polymer nanospheres and nanoparticles to inhibit the related drug resistance has attracted much attention. In this report, we have explored a novel strategy to inhibit the multidrug resistance of the targeted tumor cells by combining the unique properties of tetraheptylammonium capped Fe(3)O(4) magnetic nanoparticles with the drug accumulation of anticancer drug daunorubicin. Our results of confocal fluorescence and atomic force microscopy (AFM) as well as electrochemical studies demonstrate the remarkable synergistic effect of Fe(3)O(4) nanoparticles on drug uptake of daunorubicin in leukemia K562 cells. These observations indicate that the interaction between the magnetic nanoparticles Fe(3)O(4) and biologically active molecules on the membrane of leukemia cell lines may contribute to their beneficial effect on cellular uptake so that the synergistic enhanced effect of magnetic nanoparticles Fe(3)O(4) on drug uptake of drug resistance leukemia K562 cells could be observed upon application of the Fe(3)O(4) nanoparticles.     

A nanosized, thermo-sensitive drug carrier: self-assembled Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) magnetomicelles

Novel thermo-sensitive magnetomicelles that consist of a magnetic core, Fe(3)O(4)-oleic acid (Fe(3)O(4)-OA), and an amphiphilic surface layer of thermo-sensitive poly(oleic acid-co-N-isopropylacrylamide) P(OA-co-NIPAAm) co-polymer were prepared. Fe(3)O(4) magnetic cores functionalized with double bonds of oleic acid were prepared by suspension-oxidation reaction. Subsequently, by the co-polymerization of hydrophilic NIPAAm, hydrophobic OA and the Fe(3)O(4)-OA magnetic core, the thermo-sensitive amphiphilic polymers (P(OA-co-NIPAAm)) were grafted to obtain Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles. The surface polymeric layer of Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles would self-assemble in aqueous media to form a micellar structure attributed to the amphiphilic P(OA-co-NIPAAm) polymers. The model drug, prednisone acetate, was loaded in the magnetomicelles and in vitro release behavior of loaded drug in magnetomicelles was further investigated, which showed a thermo-sensitive release behavior due to the thermo-sensitive structural changes of the micellar surface layer.     

不规则形貌纳米 Fe3O4 介导的磁场机械力杀伤肿瘤细胞

目的 考察Fe₃O₄纳米颗粒在低频振动磁场(low-frequency vibrating magnetic field, VMF)驱动下通过磁场机械力杀伤肿瘤细胞的效果。方法 通过共沉淀法合成一种磁性强、具有不规则形貌的立方相Fe₃O₄纳米颗粒。将其置于本课题组自制的VMF中,研究其介导的磁场机械力对肿瘤细胞的杀伤效果。结果 单纯施加VMF对细胞活力无影响;加入Fe₃O₄纳米颗粒后,细胞活力随VMF处理时间和Fe₃O₄纳米颗粒浓度的增加而降低,受损细胞释放的乳酸脱氢酶也随磁场处理时间延长而增加。结论 不规则形貌Fe₃O₄纳米颗粒在VMF下可将机械力转移到肿瘤细胞,破坏细胞结构,导致细胞死亡;所采用的VMF装置结构简单、使用安全、操作方便。所采用的磁性粒子及其杀伤肿瘤细胞的方法,有临床转化潜力。     

A magnetic, reversible pH-responsive nanogated ensemble based on Fe3O4 nanoparticles-capped mesoporous silica

Stimuli-sensitive mesoporous silica nanoparticles (MSNs)-based hybrid "gate-like" ensembles capable of performing specific programmed release mode represent a new generation delivery system in recent years. In this paper, a magnetic and reversible pH-responsive, MSNs-based nanogated ensemble was fabricated by anchoring superparamagnetic Fe(3)O(4) nanoparticles on the pore outlet of MSNs via a reversible boronate esters linker. To achieve this, MSNs and Fe(3)O(4) nanoparticles were first synthesized and functionalized by polyalcohol derivative and boronic acid, respectively. The successful incorporation of Fe(3)O(4) nanoparticles onto the MSNs was confirmed by the results of XRD, TEM, XPS and N(2) adsorption-desorption method. The pH-driven "gate-like" effect was studied by in vitro release of an entrapped model dexamethasone from the pore voids into the bulk solution at different pH values. The results indicated that at pH 5-8, the pores of the MSNs were effectively capped with Fe(3)O(4) nanoparticles and the drug release was strongly inhibited. While at pH 2-4, the hydrolysis of the boroester bond took place and thus resulted in a rapid release of the entrapped drug. And by alternately changing the pH from 3 to 7, these Fe(3)O(4) cap gate could be switched "on" and "off" and thereby released the entrapped drug in a pulsinate manner (in small portions). Additionally, this nanogated release system exhibited good magnetic property, high cell biocompatibility and cellular uptake for MC3T3-E1 cells. The present data suggest that it is possible to obtain simple and very effective pH-driven pulsinate release using these Fe(3)O(4)-capped-MSNs, and this new platform represents a promising candidate in the formulation of in vivo targeted delivery of therapeutic agents to low pH tissues, such as tumors and inflammatory sites.     

三氧化二砷磁性微球的磁性能

目的:制备包裹三氧化二砷的磁性微球,分别测量磁性微球中三氧化二砷和四氧化三铁的含量,并分析其磁性能。讨论包裹三氧化二砷的磁性微球的磁靶向性效果和临床应用的可能性。 方法:采用化学共沉淀法制备四氧化三铁纳米铁磁粒子,采用w/o/w复乳法将纳米铁磁粒子和三氧化二砷包裹于聚D,L乳酸-羟基乙酸共聚物（PLGA）高分子材料中制备成磁性微球,利用全谱直读等离子体原子发射光谱仪测量磁性微球的载药量,分别测量纳米铁磁粒子和磁性微球的磁滞回线,并检验磁性微球的磁分离效果。 结果:纳米铁磁粒子和磁性微球的矫顽力和剩余磁化强度均接近零,但磁性微球的饱和磁化强度大大低于纳米铁磁粒子的饱和磁化强度。磁性微球的磁分离效果明显。 结论:合成的磁性微球外壳由PLGA高分子材料组成,纳米级四氧化三铁分散于PLGA中,壳内是三氧化二砷水溶液。磁性微球具有超顺磁性和磁靶向性。     

The targeted antibacterial and antifungal properties of magnetic nanocomposite of iron oxide and silver nanoparticles

Two types of magnetic binary nanocomposites, Ag@Fe(3)O(4) and γ-Fe(2)O(3)@Ag, were synthesized and characterized and their antibacterial activities were tested. As a magnetic component, Fe(3)O(4) (magnetite) nanoparticles with an average size of about 70 nm and monodisperse γ-Fe(2)O(3) (maghemite) nanoparticles with an average size of 5 nm were used. Nanocomposites were prepared via in situ chemical reduction of silver ions by maltose in the presence of particular magnetic phase and molecules of polyacrylate serving as a spacer among iron oxide and silver nanoparticles. In the case of the Ag@Fe(3)O(4) nanocomposite, silver nanoparticles, caught at the surfaces of Fe(3)O(4) nanocrystals, were around 5 nm in a size. On the contrary, in the case of the γ-Fe(2)O(3)@Ag nanocomposite, ultrafine γ-Fe(2)O(3) nanoparticles surrounded silver nanoparticles ranging in a size between 20 and 40 nm. In addition, the molecules of polyacrylate in this nanocomposite type suppress considerably interparticle magnetic interactions as proved by magnetization measurements. Both synthesized nanocomposites exhibited very significant antibacterial and antifungal activities against ten tested bacterial strains (minimum inhibition concentrations (MIC) from 15.6 mg/L to 125 mg/L) and four candida species (MIC from 1.9 mg/L to 31.3 mg/L). Moreover, acute nanocomposite cytotoxicity against mice embryonal fibroblasts was observed at concentrations of higher than 430 mg/L (Ag@Fe(3)O(4)) and 292 mg/L (γ-Fe(2)O(3)@Ag). With respect to the non-cytotoxic nature of the polyacrylate linker, both kinds of silver nanocomposites are well applicable for a targeted magnetic delivery of silver nanoparticles in medicinal and disinfection applications.     

Solvothermal synthesis of cobalt ferrite nanoparticles loaded on multiwalled carbon nanotubes for magnetic resonance imaging and drug delivery

Multiwalled carbon nanotube (MWCNT)/cobalt ferrite (CoFe(2)O(4)) magnetic hybrids were synthesized by a solvothermal method. The reaction temperature significantly affected the structure of the resultant MWCNT/CoFe(2)O(4) hybrids, which varied from 6nm CoFe(2)O(4) nanoparticles uniformly coated on the nanotubes at 180°C to agglomerated CoFe(2)O(4) spherical particles threaded by MWCNTs and forming necklace-like nanostructures at 240°C. Based on the superparamagnetic property at room temperature and high hydrophilicity, the MWCNT/CoFe(2)O(4) hybrids prepared at 180°C (MWCNT/CoFe(2)O(4)-180) were further investigated for biomedical applications, which showed a high T(2) relaxivity of 152.8 Fe mM(-1)s(-1) in aqueous solutions, a significant negative contrast enhancement effect on cancer cells and, more importantly, low cytotoxicity and negligible hemolytic activity. The anticancer drug doxorubicin (DOX) can be loaded onto the hybrids and subsequently released in a sustained and pH-responsive way. The DOX-loaded hybrids exhibited notable cytotoxicity to HeLa cancer cells due to the intracellular release of DOX. These results suggest that MWCNT/CoFe(2)O(4)-180 hybrids may be used as both effective magnetic resonance imaging contrast agents and anticancer drug delivery systems for simultaneous cancer diagnosis and chemotherapy.     

血管生成靶向纳米粒子c(RGDyK)@SiO2@Fe3O4的合成及生物性能*

背景：SiO2含有较多的羟基官能团,可进一步功能化而与靶向性配体相偶联,从而拓展Fe3O4@SiO2纳米粒子在生物医药领域的应用。 目的：探讨靶向性纳米粒子c(RGDyK)@SiO2@Fe3O4)的合成方法,并对其性能进行测试。 方法：采用一壶化学共沉淀法合成油酸修饰的疏水性Fe3O4纳米粒子,采用反相微乳液法合成生物相容性Fe3O4@SiO2复合纳米粒子;以3-氨丙基三乙氧基硅烷为偶联剂将复合粒子中SiO2表面的羟基氨基化、醛基化,加入1.0 mg c(RGDyK)多肽,超声震荡下反应生成c(RGDyK)@SiO2@Fe3O4纳米粒子。将Fe3O4@SiO2或c(RGDyK)@SiO2@Fe3O4与人脐静脉细胞融合细胞(EA.hy926)共培养24,48,72 h进行检测。 结果与结论：实验合成的Fe3O4@SiO2复合纳米粒子的平均粒径为40 nm,应用3-氨丙基三乙氧基硅烷可将c(RGDyK)成功耦合于复合粒子的SiO2表面。Fe3O4@SiO2或c(RGDyK)@SiO2@Fe3O4与EA.hy926共培养24 h,EA.hy926细胞活性明显增高(P < 0.05),以c(RGDyK)@SiO2@Fe3O4的作用更明显;共培养72 h后,细胞活性在各组间差异无显著性意义    (P > 0.05)。电镜观察发现,EA.hy926细胞对靶向性c(RGDyK)@SiO2@Fe3O4粒子的吞噬能力明显强于非靶向性Fe3O4@SiO2粒子。说明实验合成的c(RGDyK)@SiO2@Fe3O4纳米粒子具有良好的生物相容性、超顺磁性及较高的血管内皮细胞靶向性,是一种优良的生物材料。