磁性壳聚糖微球研究进展

磁性高分子微球是指用高分子材料将磁性金属或磁性金属氧化物的超细微粒包裹起来形成的微粒[1].因而磁性微球具备了高分子及磁性物质的双重特性,一方面具有超顺磁性,能在外加磁场下快速分离;另一方面,有与生物活性物质反应的特殊功能基团,可以作为生物活性物质的载体.正因为磁性微球的优良特性,其被广泛应用于医药行业(靶向、临床诊断、标记)、生物工程(固化酶、细胞筛选),环境工程(废水处理)等多个领域,显现出了广阔的发展前景.     

磁性阿克拉霉素A聚氰基丙烯酸正丁酯纳米微粒在正常小鼠体内靶向研究

目的：考察自行制备的纳米级磁性阿克拉霉素微粒在有无外加磁场的情况下在正常小鼠肾脏的组织分布。方法：将正常小鼠分为3组，每组6只。3组小鼠尾静脉注射磁性阿克拉霉素纳米微粒，其中，第2、3组左肾部位分别外加2000Gs和4500Gs永磁铁，用高效液相色谱法分别测定3组小鼠30min时的左、右肾脏的阿克拉霉素浓度。结果：磁性阿克拉霉素纳米微粒体内具有良好的磁响应性。应用磁性阿克拉霉素纳米微粒给药，药物在靶向脏器的浓度明显高于普通水溶液给药，且靶器官药物浓度与外加磁场强度呈正相关性。结论：磁性阿克拉霉素纳米微粒在体内具有良好的磁响应性。作为肿瘤化疗药物的新型载体，磁性纳米微粒在外加磁场的作用下，能有效提高靶向器官内药物浓度。     

环形精氨酸-甘氨酸-天冬氨酸多肽的核素标记及在健康动物体内的实验

目的：探讨^99Tc^m直接标记环形RGD-4CK九肽的可行性，观察^99Tc^m-RGD-4CK在健康动物体内的药代动力学、生物分布特点及显像表现。 方法：实验于2004—10／2005-11在解放军第三军医大学西南医院核医学中心完成。①采用预锡化法^99Tc^m直接标记RGD-4CK，3MM色谱纸层析测定标记率，通过HPLC分析、SepPakC18柱层析、体外稳定性实验、半胱氨酸置换实验及血清蛋白结合实验，评价^99Tc^m-RGD-4CK的放射化学性质。②选取雄性日本大耳兔9只，每只静脉注射37MBq^99Tc^m-RGD-4CK，分别于1．5，3．0，5．0，10，30，60，90，120，180，240min采血、称重并测定血样品放射性计数，结果经参考源校正后以MBq／L表示，所得数据应用DAS软件处理，结合α，β3受体在正常体内实际表达情况判断室模型。③选取小鼠40只，随机分为8组（n=5），每只静脉注射0．74MBq^99Tc^m—RGD-4CK，分别于1，5，20，60，90，120，180，240min处死小鼠，采集血液、心、肺、肝、肾、肠、肌肉、骨、脑，称重并测定放射性计数，结果经参考源校正后以每克组织百分注入剂量（％ID／g）表示。④选取雄性日本大耳兔3只，每只静脉注射37MBq^99Tc^m-RGD-4CK，应用SPECT进行显像，结合感兴趣时间-放射性曲线分析，观察家兔体内放射性的动态分布变化。 结果：40只小鼠和12只兔全部进入结果分析。①^99Tc^m-RGD-4CK标记率为（97．8&;#177;0．4）％，比活度为（11．90&;#177;0．05）PBq／mol；HPLC保留时间与洗脱液放射峰值时间基本一致，室温放置6h的放射化学纯度仍〉95％；SepPakC18柱层析游离^99Tc^m仅比纸层析高0．5％；与300mmol／L半胱氨酸37℃温育1h，游离^99Tc^m仅增加1．88％；^99Tc^m-RGD-4CK与血清蛋白无明显结合。^99Tc^m-RGD-4CK在健康家兔体内的药代动力学符合权重数为1／C的二室模型，分布相半衰期为（4．18&;#177;2．17）min，消除相半衰期为（69．32&;#177;0．00）min。③小鼠血液放射性清除迅速，通过肾脏排泄且快，其余组织器官放射性均随时间逐渐降低，而脑始终呈最低放射水平。④家兔SPECT显像示：各组织器官T—A曲线均随时间逐渐下降，与肾、心、肝相比，肺、胃、肌肉曲线呈低水平；1min双肾即显影，5min心、肝影开始减弱，肺放射性分布均匀，强度低于肝脏，膀胱显影；5min后膀胱影持续增强，20min后软组织影逐渐减弱；胆囊未显影，腹部呈持续低放射分布，胃区始终呈放射性缺损，颈部未见明显核素浓聚。 结论：^99Tc^m-RGD-4CK制备方法简便，标记率高（〉95％），具有良好的放射化学性质，体内稳定性好，具有比较理想的体内动力学。     

^99Tc^m-H-Annexin V动物体内分布及显像

目的：探讨^99Tc^m标记重组改良型人膜联蛋白V（H—Annexin V）在健康小鼠体内的生物分布及在健康家兔体内的动态显像表现。方法：以^99Tc^m直接标记H—Annexin V，然后测定标记率，并计算其比活度。研究^99Tc^m-H-Annexin V于1，10．30．60，120和240min在健康小鼠体内的生物分布特性；通过SPECT显像，运用感兴趣区（ROI）时间-放射性曲线分析，观察在240min内^99Tc^m-H-Annexin V在健康家兔体内的动态分布变化。结果：^99Tc^m-H—Annexin V标记率为（96．80±0．35）％，比活度为（12．30±0．06）TBq／mmol。小鼠血液放射性清除迅速，肾脏排泄较快，其余组织器官放射性均随时间逐渐降低，而脑放射性水平始终最低；家兔各器官放射性均随时间逐渐下降，与同一时间肾、心、肝相比，肺、胃、肌肉放射性呈低水平。结论：^99Tc^m-H—Annexin V制备方法简便．标记率高，体内稳定性好，具有比较理想并符合实际的动物体内动力学表现。     

磁性平阳霉素微球在海绵状血管瘤白兔体内分布的实验研究

设定新西兰白兔头部为一靶区，外加磁场，经兔耳缘静脉注射磁性平阳霉素微球（ＭＰＭＳ），观察ＭＰＭＳ在体内分布情况。并阐述外加磁场强度及时间对微球在靶区定位的影响。结果提示：１经外加磁场作用下的ＭＰＭＳ有较好的靶向分布性，且与外加磁场作用的时间、强度相平行。２海绵状血管瘤与周围的动静脉存在广泛交流，瘤腔注药后往往迅速流失，ＭＰＭＳ在外加磁场作用下，可将药物浓集在瘤腔，通过药物缓释作用，延长对瘤腔内膜的     

奥曲肽定位诊断肝癌的实验研究

目的探讨和评价放射性同位素标记奥曲肽（^99mTc-HTOC）在肝癌荷瘤鼠中的组织分布及肿瘤摄取率。方法对肝癌荷瘤鼠先后进行^99mTc-奥曲肽^99mTc-HTOC）全身显像，并观察奥曲肽（Octreotide）在肿瘤组织和其他正常组织器官的组织分布情况。结果放射性核素^99mTc标记奥曲肽（Octreotide）后的放化纯度均〉95％：在肿瘤组织中有良好的组织摄取率，在体外，^99mTc-HTOC与SSTR。有高的亲和力（kd为1-2.5nmol／L），并迅速进入SSTR；阳性的细胞。在荷瘤小鼠的研究中，肿瘤细胞高度摄取^99mTc-HTOC给药后4h为9.7％ID／g，而肾脏滞留较低。结论^99mTc-HTOC对荷瘤鼠摄像以了解放射标记奥曲肽在肿瘤及其重要器官的摄取情况，为肝癌的靶向治疗提供生物学依据。     

磁性平阳霉素微球在海绵状血管瘤白兔体内分布的实验研究

设定新四兰白兔头部为一靶区,外加磁场,经兔耳缘静脉注射磁性平阳霉素微球（NPMS）,观察MPMS在体内分布情况。并阐述外加磁场强度及时间对微球在靶区定位的影响。结果提示：①经外加磁场作用下的MPMS有较好的靶向分布性,且与外加磁场作用的时间、强度相平行。②海绵状血管瘤与周围的动静脉存在广泛交通,瘤腔注药后往往迅速流失,MPMS在外加磁场作用下,可将药物浓集在瘤腔,通过药物缓释作用,延长对瘤腔内膜的损伤作用,增加治疗效果。     

磁性碳纳米管载附5-氟尿嘧啶对结肠癌淋巴结转移的靶向抑制作用

背景:将碳纳米管制备成磁靶向药物载体后,在磁场作用下能更好地把药物运送至体内靶器官或靶组织。目的:观察磁性碳纳米管新化疗载体对结肠癌淋巴结转移的抑制效果。方法:MTT法检测5-氟尿嘧啶、磁性多壁碳纳米管-5-氟尿嘧啶、磁性多壁碳纳米管(每种药物分别含0.0003,0.003,0.03,0.3,3g/L5-氟尿嘧啶)对结肠癌SW480细胞的抑制作用。将含相同浓度5-氟尿嘧啶的5-氟尿嘧啶、磁性多壁碳纳米管-5-氟尿嘧啶、磁性多壁碳纳米管分散液分别注入SD大鼠足垫皮下及结肠癌淋巴结转移裸鼠体内。结果与结论:体外各质量浓度的5-氟尿嘧啶和磁性多壁碳纳米管-5-氟尿嘧啶对癌细胞的毒性存在剂量依赖性,相同5-氟尿嘧啶质量浓度时两者对体外SW480细胞的抑制作用无明显差异,说明磁性多壁碳纳米管-5-氟尿嘧啶的主要药效成分为5-氟尿嘧啶。体内研究高效液相检测显示磁性多壁碳纳米管-5-氟尿嘧啶能有效聚集在淋巴结,长时间持久释放,淋巴结浓集效果明显优于5-氟尿嘧啶(P<0.05),且不良反应小,肉眼容易辨识,细胞穿透性好;TUNNEL检测见磁性多壁碳纳米管-5-氟尿嘧啶化疗后结肠癌淋巴结转移灶细胞有明显凋亡现象,在磁场作用下效果更显著。说明磁性多壁碳纳米管-5-氟尿嘧啶对结肠癌SW480细胞淋巴结转移有明显抑制作用。     

小儿消化道出血99Tcm-高锝酸盐对异位胃黏膜显像的特征

目的：研究小儿消化道出血^99Tc^m－高锝酸盐异位胃黏膜的显像特征，建立美克尔憩室和小肠重复畸形影像学的诊断标准。方法：对141例消化道出血患儿作了^99Tc^m－高锝酸盐异位胃黏膜显像，按7．4MBq/kg静脉注射^99Tc^m－高得锝酸盐，以脐为中心进行动态17min和静态30min或1h的采集。结果：141例患儿中59例显像阳性，阳性检出率为41．8％。141例消化道出血中，经手术和病理证实了48例。其中美克尔憩室18例，形态呈小圆形或近似小圆形1－3cm的异常浓集区。小肠重复畸形22例，其中呈条索肠袢状12例，团块状5例，4cm以上大圆形异常浓集区4例。食管、胃重复畸形3例。在48例患儿中，假阴性率为2．08％（小肠重复畸形1例），假阳性5例，为10．42％。结论：美克尔憩室与小肠重复畸形在^99Tc^m－高锝酸盐异位胃黏膜显像中，有特征性影像学表现。     

超顺磁性纳米颗粒治疗肿瘤的应用进展

背景,近年来纳米颗粒在肿瘤热疗、基因载体研究、靶向药物治疗等方面得到迅速发展,特别是纳米颗粒载药系统已成为肿瘤治疗的又一突破口.目的:对超顺磁性纳米颗粒在医学领域特别是肿瘤治疗方面的应用及其机制进行概述.方法:应用计算机检索Medline数据库(2000-01/2009-10),以"Superparamagnetic,Nanoparticles,Targeting"为检索词;应用计算机检索中国期刊网(CNKI)(2005-01/2009-10),万方数据库(2005-01/2009-10),以"磁性、纳米颗粒、靶向"为检索词.结果与结论:共收集123篇关于磁性纳米颗粒靶向作用的文献,中文24篇,英文108篇.排除发表时间较早、重复及类似研究,纳入30篇符合标准的文献.超顺磁性纳米颗粒是指具有磁响应性的纳米级粒子,其直径一般小于30 nm,当磁性纳米粒子的粒径小于其超顺磁性临界尺寸时,粒子进入超磁性状态.超顺磁性纳米颗粒除了通过血液循环进入炎症肿瘤相关部位外,还可被广泛存在于肝脏、脾脏、淋巴结的网状细胞-内皮吞噬系统(reticulo-eneothelial system,RES)的细胞所识别.研究发现经过表面修饰的载药纳米颗粒,可跨血脑屏障转运,其机制可能与血脑屏障的连接结构--毛细血管,其内皮细胞通过低密度脂蛋白介导的胞吞作用有关.目前合成生物相容性磁性纳米颗粒的方法有很多,但最常用的合成生物相容Fe3O4磁性纳米颗粒的方法为共沉淀法.超顺磁性纳米颗粒在外加磁场的作用下可具有靶向性,且四氧化三铁的晶体对细胞无毒,其作为基因载体及药物载体被广泛应用于医学研究,为肿瘤的治疗开辟了新的途径.但对于外置磁场,如何全面的避开内皮吞噬系统的吞噬,防止治疗过程中药物性血栓的生成等尚存在不足.     

人工椎体的组织相容性和力学性能

背景：近年来,随着组织工程学的发展,椎体替代材料趋于多样化,学者们不再满足于其能否恢复椎体高度与即刻稳定性,而是更为关注远期的融合,良好的组织相容性和力学性能。目的：分析国内人工椎体的组织相容性和力学性能。方法：以＂人工椎体、相容性、生物力学＂为检索词在中国期刊全文数据库中检索与人工椎体生物相容性和生物力学研究相关的文献进行分析。结果与结论：人工椎体组织相容性的动物实验显示,纳米羟基磷灰石/聚酰胺66复合人工椎体成分和结构与人体骨相似,具有良好的生物相容性,成骨活性;可发生生物降解,其降解作用与成骨能力匹配。人工椎体的生物力学研究显示出纳米羟基磷灰石/聚酰胺66复合人工椎体不仅具有良好的生物活性,而且具有良好的轴向压缩载荷和椎间支撑能力,力学性能优异。生物陶瓷人工椎体不仅具有良好的生物相容性,而且在治疗椎体肿瘤中有靶向定位作用;金属材料的人工椎体经过多年的改进,其生物相容性亦可满足临床要求。就各类型人工椎体优劣而言,仍需进一步大量研究和实践,就其临床应用而言,需根据临床需要进行选择。     

Increased transverse relaxivity in ultrasmall superparamagnetic iron oxide nanoparticles used as MRI contrast agent for biomedical imaging

Synthesis of a contrast agent for biomedical imaging is of great interest where magnetic nanoparticles are concerned, because of the strong influence of particle size on transverse relaxivity. In the present study, biocompatible magnetic iron oxide nanoparticles were synthesized by co‐precipitation of Fe²⁺ and Fe³⁺ salts, followed by surface adsorption with reduced dextran. The synthesized nanoparticles were spherical in shape, and 12 ± 2 nm in size as measured using transmission electron microscopy; this was corroborated with results from X‐ray diffraction and dynamic light scattering studies. The nanoparticles exhibited superparamagnetic behavior, superior T₂ relaxation rate and high relaxivities (r₁ = 18.4 ± 0.3, r₂ = 90.5 ± 0.8 s^?1 mM^?1, at 7 T). MR image analysis of animals before and after magnetic nanoparticle administration revealed that the signal intensity of tumor imaging, specific organ imaging and whole body imaging can be clearly distinguished, due to the strong relaxation properties of these nanoparticles. Very low concentrations (3.0 mg Fe/kg body weight) of iron oxides are sufficient for early detection of tumors, and also have a clear distinction in pre‐ and post‐enhancement of contrast in organs and body imaging. Many investigators have demonstrated high relaxivities of magnetic nanoparticles at superparamagnetic iron oxide level above 50 nm, but this investigation presents a satisfactory, ultrasmall, superparamagnetic and high transverse relaxivity negative contrast agent for diagnosis in pre‐clinical studies. Copyright © 2016 John Wiley & Sons, Ltd.     

人工椎间盘置换对腰椎小关节应力影响的三维有限元分析

背景:近年来随着对脊柱生物力学研究的深入,人工椎间盘被认为是治疗腰椎退行性变较理想的方法,但目前对人工腰椎间盘的生物力学研究还非常有限.目的:建立腰椎运动节段人工椎间盘置换的三维有限元模型并进行生物力学分析,观察人工椎间盘置换对腰椎小关节应力的影响.方法:在已建立的正常腰椎运动节段三维有限元模型的基础上去除L4～5椎间盘、上下终板的有限元单元,加入SB-Chaite Ⅲ型人工椎间盘的有限元模型,保留L4～5椎间隙的纤维环及相关韧带,形成L4～5运动节段人工椎间盘置换的三维有限元模型.对三维有限元模型在垂直压缩、前屈、后伸、侧弯等不同载荷下进行生物力学分析,记录小关节的应力,并与正常运动节段三维有限元模型相应部位的应力进行对比.结果与结论:生物力学分析结果显示,人工椎间盘置换后:①垂直压缩时上下椎体、双侧小关节内应力与正常节段相比差异无显著性意义(P > 0.01).②前屈、后伸时上下椎体前、后方及双侧小关节内应力与正常节段相比差异无显著性意义(P > 0.01).③侧弯时上下椎体左右两侧及双侧小关节内应力与正常节段相比差异无显著性意义(P > 0.01).提示人工腰椎间盘置换后小关节应力可保持在正常运动节段的水平,人工腰椎间盘置换可以达到腰椎生物力学性能重建的目的.     

Can we accurately quantify nanoparticle associated proteins when constructing high‐affinity MRI molecular imaging probes?

Targeted magnetic resonance contrast agents (e.g. iron oxide nanoparticles) have the potential to become highly selective imaging tools. In this context, quantification of the coupled amount of protein is essential for the design of antibody‐ or antibody fragment‐conjugated nanoparticles. Nevertheless, the presence of magnetic iron oxide nanoparticles is still an unsolved problem for this task. The aim of the present work was to clarify whether proteins can be reliably quantified directly in the presence of magnetic iron oxide nanoparticles without the use of fluorescence or radioactivity. Protein quantification via Bradford was not influenced by the presence of magnetic iron oxide nanoparticles (0–17.2 mmol Fe l^?1). Instead, bicinchoninic acid based assay was, indeed, distinctly affected by the presence of nanoparticle‐iron in suspension (0.1–17.2 mmol Fe l^?1), although the influence was linear. This observation allowed for adequate mathematical corrections with known iron content of a given nanoparticle. The applicability of our approach was demonstrated by the determination of bovine serum albumin (BSA) content coupled to dextrane‐coated magnetic nanoparticles, which was found with the QuantiPro Bicinchoninic acid assay to be of 1.5 ± 0.2 µg BSA per 1 mg nanoparticle. Both Bradford and bicinchoninic acid assay protein assays allow for direct quantification of proteins in the presence of iron oxide containing magnetic nanoparticles, without the need for the introduction of radioactivity or fluorescence modules. Thus in future it should be possible to make more precise estimations about the coupled protein amount in high‐affinity targeted MRI probes for the identification of specific molecules in living organisms, an aspect which is lacking in corresponding works published so far. Additionally, the present protein coupling procedures can be drastically improved by our proposed protein quantification method. Copyright © 2011 John Wiley & Sons, Ltd.     

带翼可调节置换系统在下颈椎骨折脱位中的应用

背景：ADDplus-带翼可调节置换系统具有人工椎体和前路固定板一体化、人工椎体高度可调的特点,以及操作简单、手术时间短、组织相容性好等优势越来越受到外科医生的信赖。目的：观察带翼可调节置换系统在颈椎前路减压、植骨融合及置入固定治疗下颈椎骨折脱位合并脊髓损伤中的疗效。方法：采用ADDplus-带翼可调节置换器对12例下颈椎骨折脱位合并脊髓损伤患者进行前路切开复位、减压、植骨融合内固定治疗。治疗3,6,12个月分别进行临床评估和影像学检查,此后,每年检查1次。结果与结论：平均随访18个月过程中,获得牢固的骨性融合,调节器体内位置良好、无松动断裂,颈椎椎间高度和生理曲度纠正,术后患者感觉、运动功能的恢复得到较大幅度提升。1例出现低钠血症,其余患者无术后并发症。因此可以认为,采用带翼可调节置换器行颈椎前路切开复位、内固定减压、植骨融合治疗下颈椎骨折脱位并脊髓损伤,操作安全、简单、材料生物相容性好、内固定疗效确切。     

超顺磁性氧化铁纳米粒子在脑磁共振成像中的应用

超顺磁性氧化铁纳米粒子的磁性及生物相容性,使其在生物医学多个领域的应用研究都逐渐发展起来。本文介绍磁共振成像（MRI）及脑功能磁共振成像（fMRI）基本原理。列举不同性能的磁性氧化铁粒子作为磁共振成像对比剂在脑科学应用中的研究进展。表面结合单克隆抗体、蛋白质、多肽、核苷酸分子或其它特殊聚合物的磁性氧化铁粒子具有吸收特异性（靶向性）,结合MRI可实现对脑部病变前期改变、药物输运及治疗的监测,对细胞、生物分子包括mRNA的成像及探测。经葡聚糖或聚乙二醇修饰的超顺磁性氧化铁纳米粒子血液半衰期较长,可作为对比剂用于脑fMRI成像。控制氧化铁纳米粒子的粒度及表面修饰物的物理化学性质、提高饱和磁化强度、借以接枝以各种靶向性的物质、开发具有荧光-磁性等多种性能的复合纳米粒子及掌握纳米粒子与生物分子、细胞、及生物组织之间的相互作用,则需要更深入的研究。     

Development of magnetic chromatography to sort polydisperse nanoparticles in ferrofluids

Whatever the strategy of synthesis, nanoparticles in magnetic fluids commonly feature a broad size distribution. However, the presence of several size populations in ferrofluids is often problematic because of the close relationship between the efficiency of the nanoparticles and their physicochemical properties. In this work, a magnetic size sorting procedure is developed in order to reduce this polydispersity, using the magnetic properties of the iron oxide nanoparticles. This magnetic sorting with an adjustable magnetic field allows isolation of the small superparamagnetic particles as well as the larger particles. Magnetometry, nuclear magnetic relaxation dispersion profiles and transmission electron microscopy were successfully used to check the efficiency of the magnetic sorting procedure, which was shown to work as a ‘magnetic’ chromatography. Copyright © 2010 John Wiley & Sons, Ltd.     

Doxorubicin-loaded mesoporous magnetic nanoparticles to induce apoptosis in breast cancer cells

Selective targeting of chemotherapeutic drugs toward the cancer cells overcomes the limitations involved in chemotherapy. Ideally, targeted delivery system holds great potential in cancer therapy due to specific release of drug in the cancer tissues. In this regard, DOX-loaded chitosan coated mesoporous magnetic nanoparticles (DOX-CMMN) were prepared and evaluated for its physicochemical and biological characteristics. Nanosized magnetic nanoparticles were observed with a high loading capacity for DOX. The drug-loaded nanoparticles exhibited a controlled and sustained release of drug without any burst release phenomenon. The DOX-DMMN showed a concentration-dependent cell proliferation inhibitory action against breast cancer cells. The blank nanoparticles showed excellent biocompatibility with cell viability >85% at the maximum tested concentration. Our results showed that chitosan coated magnetic system has high potential for breast cancer targeting under an alternating current magnetic field (ACMF). The present study showed that magnetic nanoparticles can be targeted to tumor cells under the presence of oscillating magnetic field. The combined effect of chemotherapy and thermotherapy can have a promising clinical potential for the treatment of breast cancer.     

Brain tumor targeting of magnetic nanoparticles for potential drug delivery: Effect of administration route and magnetic field topography

Our previous studies demonstrated feasibility of magnetically-mediated retention of iron oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350 mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, R_d. The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of R_d.