氧化铁纳米颗粒对巨噬细胞极化效应影响的研究进展

巨噬细胞是机体免疫系统中重要的免疫效应细胞,具有显著的可塑性和异质性,在正常生理条件下和炎症反应过程中均发挥着重要作用。研究发现,巨噬细胞极化涉及多种细胞因子,是免疫调控的关键环节。纳米颗粒靶向巨噬细胞可对多种疾病的发生发展产生一定影响,其中氧化铁纳米颗粒因其特性被作为癌症诊断和治疗的介质与载体,可充分利用肿瘤的特殊微环境,将药物主动或被动地聚集于肿瘤组织,具有良好的应用前景。但利用氧化铁纳米颗粒重编程巨噬细胞的具体调控机制仍需深入探究。本文首先阐述了巨噬细胞的分类、极化效应及代谢机制,其次对氧化铁纳米颗粒的应用以及诱导巨噬细胞重编程进行综述,最后讨论了氧化铁纳米颗粒的研究前景和面临的困难与挑战,为进一步探讨纳米颗粒对巨噬细胞极化效应的机制研究提供基础数据和理论支持。     

氧化铁纳米颗粒对静止状态白血病细胞的作用研究

目的 研究二巯基丁二酸修饰的四氧化三铁纳米颗粒(DMSA-Fe₃O₄NPs)对静止状态白血病细胞的作用及机制。方法 利用透射电镜观察纳米颗粒形貌;用低血清培养基诱导细胞进入静止状态,采用普鲁士蓝染色法与邻二氮菲铁定量法检测DMSA-Fe₃O₄NPs进入Kasumi-1细胞的情况;通过乳酸脱氢酶法、细胞氧化应激荧光探针和凋亡检测试剂分析DMSA-Fe₃O₄NPs对Kasumi-1细胞的作用。结果 DMSA-Fe₃O₄NPs可进入静止状态的Kasumi-1细胞,细胞内铁含量与DMSA-Fe₃O₄NPs浓度成正比;与此同时,细胞活性降低,细胞内活性氧(reactive oxygen species,ROS)与脂质过氧化物水平升高,细胞发生凋亡。正常培养的Kasumi-1细胞活性和氧化应激水平不受DMSA-Fe₃O₄NPs的影响。结论...     

超顺磁性氧化铁纳米颗粒在药物靶向递送中的研究进展

超顺磁性氧化铁(SPIO)是一种新型的生物医学纳米材料,具有表面效应、小尺寸效应和宏观量子隧道效应,而较好的生物相容性及超顺磁性使其广泛用于疾病的靶向治疗.相比于其他纳米药物载体,超顺磁性氧化铁纳米颗粒(SPIONs)因其内在属性如固有磁性、良好的安全性及制备和表面修饰方法的可用性等在纳米药物领域中显示出巨大潜力,为其多样的生物医学应用铺平了道路.但研究人员对其不可预知的毒性、改变细胞信号转导和基因表达等方面仍有顾虑.对SPIONs在药物靶向递送中的研究进展作一综述.     

氧化铁纳米颗粒引起肝血窦内皮细胞损伤及其机制研究

研究二巯基丁二酸修饰的Fe₃O₄纳米颗粒(DMSA-Fe₃O₄)对人原代肝血窦内皮细胞(HHSECs)的作用及对肝脏的影响。利用透射电镜和纳米颗粒追踪分析仪表征纳米颗粒尺寸和表面性质。采用实时无标记细胞分析技术、流式细胞术、实时荧光定量PCR技术和普鲁士蓝染色法等方法,检测0～200 μg/mL浓度范围内DMSA-Fe₃O₄对HHSECs的作用。将DMSA-Fe₃O₄(剂量为1 mg/kg)通过尾静脉注射到小鼠体内,分析肝脏的损伤情况。细胞实验重复数为3,动物实验每组4只动物。结果表明,HHSECs对DMSA-Fe₃O₄的摄取具有浓度和时间依赖性,细胞活性最低降到对照组的37.3%。DMSA-Fe₃O₄引起细胞ROS升高,是对照组的1.41倍;促进HO-1基因表达升高,是对照组的20.8倍;引起HIF-1α基因表达升高,是对照组的2.01倍;促进VEGF基因的表达升高,是对照组的4.2倍。4次静脉注射DMSA-Fe₃O₄后的第2 d,可观察到小鼠肝脏内皮细胞和库普弗细胞有DMSA-Fe₃O₄蓄积,并伴有肝组织染色变浅、少量肝细胞坏死;第158 d时,肝脏中蓄积的DMSA-Fe₃O₄明显减少,肝脏组织恢复正常形态。以上结果显示,HHSECs可大量摄取氧化铁纳米颗粒,引起细胞活性降低和氧化应激损伤。体内多次静脉注射的DMSA-Fe₃O₄可蓄积在肝脏中,伴有肝损伤。随着时间延长,纳米颗粒从肝脏中排出,肝脏损伤可以恢复。     

银纳米颗粒对神经元的毒性研究

目的 研究不同浓度的银纳米颗粒对神经元毒性的剂量-效应关系,探索银纳米颗粒对神经元的毒性机理.方法 首先培养一种活性好、生长状态优良的原代神经元,将不同浓度（2.5～500μg/mL）的银纳米颗粒加入神经元中作用24h后,通过MTT法计算细胞增殖率,并分析不同浓度的银纳米颗粒对神经元毒性的剂量-效应关系.结果 在25～250μg/mL范围内,细胞数量与形态呈现不同的变化,银纳米颗粒浓度与细胞增殖率呈负相关.结论 在25～250μg/mL的浓度范围内,银纳米颗粒对神经元细胞的毒性呈剂量-效应关系.     

介孔二氧化硅纳米颗粒的生物相容性

背景：介孔二氧化硅纳米颗粒具有很多优异的物理性质,在生物医学领域应用广泛,但目前对其生物相容性研究不足。 目的：综述国内外对介孔二氧化硅纳米颗粒生物相容性的研究进展。 方法：检索PubMed、EMBASE、万方、CNKI、维普、中国生物医学数据库有关介孔二氧化硅纳米颗粒细胞毒性和动物毒性的相关文献。 结果与结论：介孔二氧化硅纳米颗粒可通过内吞作用被细胞摄取,其可能通过在细胞内产生活性氧化物导致细胞毒性;介孔二氧化硅纳米颗粒致细胞毒作用与介孔二氧化硅纳米颗粒浓度、颗粒尺寸、表面活性剂去除方式、细胞种类有关。介孔二氧化硅纳米颗粒在动物体内主要富集在肝脏和脾脏,尿液和粪便是其主要排泄途径;介孔二氧化硅纳米颗粒在体内局部生物相容性良好,而大剂量介孔二氧化硅纳米颗粒经腹腔注射或静脉注射可导致严重全身反应。介孔二氧化硅纳米颗粒在体外和体内均显示出较好的生物相容性,但其安全性仍需进一步研究。     

纳米氧化铁、纳米TiO2、碳纳米管的毒理学研究进展

纳米材料的广泛应用使研究者、生产者和消费者将有更多的机会接触纳米材料。纳米粒子可经多种途径进入人体,其是否会影响人类健康引起了广泛关注。纳米TiO2和碳纳米管在工业及商业有着广泛的应用前景,纳米氧化铁是磁共振成像诊断、磁性药物载体及肿瘤靶向定位治疗的热门生物材料。分析综述了纳米氧化铁、纳米TiO2和碳纳米管三种材料的毒理学研究结果,并提出了在纳米毒理学研究目前亟待解决的重要问题。     

磁性载药纳米颗粒在癌症化学治疗中的发展现状

癌症是致死率最高的疾病之一,癌症的治疗一直以来都是临床医学中的重点研究课题。化学治疗作为最常采用的治疗方法有效却也存在许多弊端,因为大多数化疗药物缺乏选择性和靶向性,会对人体的健康造成不必要的影响,因此纳米药物递送系统在治疗癌症的研究中发挥着重要的作用。而磁性纳米颗粒作为纳米药物递送系统的其中一类载体,既具有粒径小、比...     

磁性纳米颗粒介导基因转染的研究进展

介绍了磁性纳米颗粒介导基因转染的最新研究进展,面临的主要问题以及将来的发展方向.     

纳米颗粒对免疫细胞调控的研究进展

特异性免疫治疗已成为预防和治疗多种疾病的有效策略,如肿瘤、自身免疫病等。近年来,研究人员不断探索具有新结构和新性能的纳米颗粒在临床的应用。本文综述了纳米颗粒通过调控调节性T细胞、自然杀伤细胞及树突状细胞等在维持自身免疫稳态方面的作用,可能成为未来治疗肿瘤、自身免疫病等的新策略。     

Endocytotic uptake of iron oxide nanoparticles by cultured brain microglial cells

Microglia are the phagocytotic cells of the brain that respond rapidly to alterations in brain homeostasis. Since iron oxide nanoparticles (IONPs) are used for diagnostic and therapeutic applications in the brain, the consequences of an exposure of microglial cells to IONPs are of particular interest. To address this topic we have synthesized and characterized fluorescent BODIPY®-labelled IONPs (BP-IONPs). The average hydrodynamic diameter and the ζ-potential of BP-IONPs in water were ～65 nm and ?49 mV, respectively. Both values increased after dispersion of the particles in serum containing incubation medium to ～130 nm and ?8 mV. Exposure of cultured rat microglial cells with BP-IONPs caused a time-, concentration- and temperature-dependent uptake of the particles, as demonstrated by strong increases in cellular iron contents and cellular fluorescence. Incubation for 3 h with 150 and 450 μM iron as BP-IONPs increased the cellular iron content from a low basal level of ～50 nmol iron mg^?1 to 219 ± 52 and 481 ± 28 nmol iron (mg protein)^?1, respectively. These conditions did not affect cell viability, but exposure to higher concentrations of BP-IONPs or for longer incubation periods severely compromised cell viability. The BP-IONP fluorescence in viable microglial cells was co-localized with lysosomes. In addition, BP-IONP accumulation was lowered by 60% in the presence of the endocytosis inhibitors 5-(N-ethyl-N-isopropyl)amiloride, tyrphostin 23 and chlorpromazin. These results suggest that the rapid accumulation of BP-IONPs by microglial cells is predominantly mediated by macropinocytosis and clathrin-mediated endocytosis, which direct the accumulated particles into the lysosomal compartment.     

Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy

A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy.     

星型M-PLGA纳米药物制剂用于宫颈癌治疗的研究

目的 本研究合成了一种星型的甘露醇引发的聚（乳酸-羟基乙酸）共聚物（M-PLGA）,旨在提供一种新型的纳米制剂用于宫颈癌的治疗.方法 这种新型的共聚物通过开环聚合合成,利用核磁共振仪进行表征.采用改进的纳米沉淀法制备载多烯紫杉醇M-PLGA纳米粒并在扫描电镜下观察纳米粒的形态.结果 M-PLGA纳米粒粒径分布较窄,在人宫颈癌Hela细胞中的摄取水平要高于PLGA纳米粒.载多烯紫杉醇的M-PLGA纳米粒对Hela细胞的毒性显著高于商用的泰素帝和载多烯紫杉醇的PLGA纳米粒,证明星型M-PLGA聚合物作为纳米药物载体优于线型PLGA聚合物;同时,星型M-PLGA的载药量也明显高于线型聚合物.结论 星型M-PLGA共聚物可作为一种极具潜力的用于宫颈癌治疗的纳米载体材料.     

纳米颗粒与骨细胞的作用及其在骨科中的应用

生物材料在骨再生治疗及组织工程领域的应用日益广泛.基于不同的构成、大小及形状,纳米颗粒与骨细胞之间的作用具有显著的独特性.因此,详细地分析纳米颗粒对细胞功能的作用,有利于选择更适于促进骨再生的材料.通过系统回顾纳米颗粒对间充质干细胞(MSCs)、成骨细胞及破骨细胞的作用,发现纳米颗粒对这些骨相关细胞具有十分重要的影响.其在骨缺损填充、作为药物和基因运输载体等方面具有广阔的应用前景,是促进骨再生及治疗骨疾病的良好选择.     

Fe3O4纳米粒子的组织相容性及组织分布研究

BACKGROUND: Ferroferric oxide (Fe₃O₄) nanoparticles are a research hotspot in drug delivery system, which can transport antineoplastic drugs to the lesion under external magnetic field. Additionally, its submicrons even can reach the tumor site several centimeters far away from the magnetic source. OBJECTIVE: To investigate the histocompatibility and in vivo distribution of Fe₃O₄ nanoparticles and to explore its application prospect and limitations as a drug carrier in the chemotherapy of osteosarcoma. METHODS: 10.0 mg/kg Fe₃O₄ nanoparticles were administrated into Wistar rats via tail vein, then the rats were executed at 15, 60 and 120 minutes, respectively, and the rat lung, brain, heart, liver, kidney, hind limb and skeletal muscle were removed. The ferric ion content in each tissue was determined by atomic absorption spectrometer, and the morphological changes of different tissues were observed by hematoxylin-eosin staining at each time point. RESULTS AND CONCLUSION: After administrated for 15 minutes, the concentration of Fe₃O₄ nanoparticles in the liver and kidney reached peak, followed by a decrease at 60 and 120 minutes, but still remained a high level. The concentration of Fe₃O₄ nanoparticles at three time points showed significant difference compared with the control group (P < 0.05), demonstrating that the nanoparticles can be quickly enriched and long-term persistent in the liver and kidney. After administrated for 15 minutes, the concentration of Fe₃O₄ nanoparticles in the heart, lung, skeletal muscle and bone reached peak, which had significant difference compared with the control group (P < 0.05), and significantly decreased subsequently except that in the bone. This significant difference still displayed at 60 minutes between groups (P < 0.05), indicating that the nanoparticle can reach a high concentration but persist short time in the high blood perfused tissues. Compared with the control group, the concentration of Fe₃O₄ nanoparticles in the brain tissue showed no significant difference at each time point (P > 0.05), suggesting that the blood-brain barrier can inhibit the nanoparticle penetration. No overt morphological changes were found in each tissue after hematoxylin-eosin staining. In conclusion, the distribution of Fe₃O₄ nanoparticles conjugate sodium oleate in organism is influenced by the blood perfusion and mononuclear phagocyte system, and they cannot penetrate the blood-brain barrier and make no significant effect on tissues, but maintain a high level in the liver kidney and bone for a long-term, thus providing a theoretical basis for the drug delivery system in the magenetic hyperthermia therapy of malignant tumors.     

磁性四氧化三铁纳米颗粒作用于前成骨细胞的生物相容性

BACKGROUND: Investigations on toxic mechanism and safety of magnetic ferrosoferric oxide (Fe3O4) nanoparticles are extremely necessary when these nanoparticles as an emerging material for bone tissue engineering are implanted into the living body. OBJECTIVE: To investigate the biocompatibility of magnetic Fe3O4 nanoparticles with preosteoblasts. METHODS: Mouse preosteoblasts were cultured in 0, 200, 400, 800 mg/L magnetic Fe3O4 nanoparticles. After 24 hours, alkaline phosphatase activity, osteocalcin level, cell proliferation rate, cellular morphology, cytoskeleton variation, cell apoptosis and autophagy-related genes, such as Caspase-3, LC3A, LC3B, were detected by alkaline phosphatase assay kit, ELISA kit, cell counting kit-8 kit, inverted microscope, laser confocal microscopy and real-time PCR, respectively. RESULTS AND CONCLUSION: After 24 hours of culture, there ware no significant differences between 200 mg/L group and control group. However, in the groups of 400 and 800 mg/L, the ratio of alkaline phosphatase activity to total protein and osteocalcin level increased, the cell proliferation rate decreased, cellular morphology and cytoskeleton changed remarkably, LC3B expression was up-regulated compared with the control group. Additionally, there were also no significant differences in the expression of Caspase-3 and LC3A between 400 and 800 mg/L groups and control group. Therefore, magnetic Fe3O4 nanoparticles at high level contributes to cytotoxicity and up-regulation of LC3B expression, and affects cellular morphology, cytoskeleton and cell proliferation rate, although these nanoparticles can increase the osteoblastic differentiation.        

Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles

Autophagy has attracted a great deal of research interest in tumor therapy in recent years. An attempt was made in this direction and now we report that iron oxide NPs synthesized by us selectively induce autophagy in cancer cells (A549) and not in normal cells (IMR-90). It was also noteworthy that autophagy correlated with ROS production as well as mitochondrial damage. Protection of NAC against ROS clearly suggested the implication of ROS in hyper-activation of autophagy and cell death. Pre-treatment of cancer cells with 3-MA also exhibited protection against autophagy and promote cellular viability. Results also showed involvement of classical mTOR pathway in autophagy induction by iron oxide NPs in A549 cells. Our results had shown that bare iron oxide NPs are significantly cytotoxic to human cancer cells (A549) but not to the normal human lung fibroblast cells (IMR-90).In other words our nanoparticles selectively kill cancerous cells. It is encouraging to conclude that iron oxide NPs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing autophagy mediated cell death of cancer cells.     

纳米银溶胶的体外细胞毒性评价及其机制研究

目的 对纳米银溶胶的体外细胞毒性进行评价,初步探讨纳米银对细胞的毒性作用机制.方法利用化学还原法制备纳米银溶胶,通过紫外-可见分光光度计和透射电镜对其物理特性进行检测;以小鼠纤维肉瘤细胞( L929)为研究对象,通过细胞形态观察、LIVE/DEAD染色分析和MTT检测来评价纳米银对细胞的毒性作用;在电子显微镜下观察纳米...     

载阿霉素星型多臂PLGA-PEG嵌段共聚物纳米胶束的构建

目的 利用星型多臂端氨基聚乙丙交酯/聚乙二醇[4s-( PLGA-PEG-NH2)]两亲性嵌段共聚物作为载体材料,构建抗肿瘤药物阿霉素纳米胶束载药体系.方法 合成聚合物4s-( PLGA-PEG-NH2),通过核磁共振氢谱(1H NMR)和凝胶渗透色谱(GPC)对其组成、结构及相对分子质量进行表征;采用溶剂挥发法制备阿霉素(DOX)聚合物纳米胶束,并通过透射电子显微镜(TEM)、粒径分析仪及荧光分析法对载药纳米胶束进行表征;对阿霉素载药纳米胶束在HeLa细胞中的摄取及细胞毒性进行了初步评价.结果 1H NMR与GPC测定结果表明:合成的共聚物符合设计的4s-( PLGA-PEG-NH2)结构;能成功物理包埋DOX药物分子在水溶液中自组装成核-壳结构的纳米胶束,载药量约为7.5％,包埋率约为75.2％,Zeta电位为-17.6 mV;体外细胞实验显示:载阿霉素星型4臂聚合物纳米胶束[DOX-loaded 4s-(PLGA-PEG-NH2)micelles]比载阿霉素线性聚合物纳米胶束[DOX-loaded linear-( PLGA-PEG-PLGA)micelles]可更有效地被HeLa细胞摄取,并对HeLa细胞的毒性更强.结论 4s-( PLGA-PEG-NH2)阿霉素载药纳米胶束可有效提高HeLa细胞的摄取率以及对HeLa细胞的杀伤率,提示其可作为一类新型的抗肿瘤药物递送载体.     

The role of iron redox state in the genotoxicity of ultrafine superparamagnetic iron oxide nanoparticles

Ultrafine superparamagnetic iron oxide nanoparticles (USPION) hold great potential for revolutionising biomedical applications such as MRI, localised hyperthermia, and targeted drug delivery. Though evidence is increasing regarding the influence of nanoparticle physico-chemical features on toxicity, data however, is lacking that assesses a range of such characteristics in parallel. We show that iron redox state, a subtle though important physico-chemical feature of USPION, dramatically modifies the cellular uptake of these nanoparticles and influences their induction of DNA damage. Surface chemistry was also found to have an impact and evidence to support a potential mechanism of oxidative DNA damage behind the observed responses has been demonstrated. As human exposure to ferrofluids is predicted to increase through nanomedicine based therapeutics, these findings are important in guiding the fabrication of USPION to ensure they have characteristics that support biocompatibility.