A review on nanotoxicity and nanogenotoxicity of different shapes of nanomaterials

Nanomaterials (NMs) generally display fascinating physical and chemical properties that are not always present in bulk materials; therefore, any modification to their size, shape, or coating tends to cause significant changes in their chemical/physical and biological characteristics. The dramatic increase in efforts to use NMs renders the risk assessment of their toxicity highly crucial due to the possible health perils of this relatively uncharted territory. The different sizes and shapes of the nanoparticles are known to have an impact on organisms and an important place in clinical applications. The shape of nanoparticles, namely, whether they are rods, wires, or spheres, is a particularly critical parameter to affect cell uptake and site‐specific drug delivery, representing a significant factor in determining the potency and magnitude of the effect. This review, therefore, intends to offer a picture of research into the toxicity of different shapes (nanorods, nanowires, and nanospheres) of NMs to in vitro and in vivo models, presenting an in‐depth analysis of health risks associated with exposure to such nanostructures and benefits achieved by using certain model organisms in genotoxicity testing. Nanotoxicity experiments use various models and tests, such as cell cultures, cores, shells, and coating materials. This review article also attempts to raise awareness about practical applications of NMs in different shapes in biology, to evaluate their potential genotoxicity, and to suggest approaches to explain underlying mechanisms of their toxicity and genotoxicity depending on nanoparticle shape.     

磁性白蛋白纳米球作为基因载体的研究

目的 制备载基因的磁性白蛋白纳米球,评估磁性白蛋白纳米球作为基因载体的可行性及体外的磁靶向性。方法 采用去溶剂化-交联法制备载基因磁性白蛋白纳米球,分别运用透射电镜（TEM）、动态光散射分析（DLS）对其形态、粒径进行表征。应用绿色荧光蛋白基因系统（pGFP）,观察载基因磁性白蛋白纳米球体外释放基因速率的情况及转染细胞的情况。运用普鲁士蓝染色法观察磁性纳米球的体外磁靶向性。结果 载基因磁性纳米球在TEM检测下为球形,大小均匀,并且在载基因磁性纳米球中明显地观察到在电子密度较低的白蛋白纳米球中包裹着电子密度较高的磁性纳米粒。DLS显示载基因免疫磁性纳米球的水合粒径约为209nm。体外动态释放基因速率,计算其累积释放率显示,该材料13h释放基因为95.25%,曲线平缓;转染实验结果显示载基因磁性纳米球能够有效转染SMMC-7721细胞,且转染效率高于载基因纳米球。普鲁士蓝染色实验结果显示磁靶向组细胞内的铁颗粒明显多于非靶向组。结论 成功制备了载基因磁性白蛋白纳米球,具有缓释基因的作用,并且能高效转染人肝癌细胞SMMC-7721。磁性白蛋白纳米球基因载体具有体外靶向性,有望作为一种潜在的靶向基因载体应用到生物医学领域。     

Freeze-drying of itraconazole-loaded nanosphere suspensions: a feasibility study

The present study concerns the stabilization of the association of the new hydrophobic triazole derivative itraconazole within poly-ϵ-caprolactone-nanospheres by means of freeze-drying. We have investigated the freeze-drying of nanospheres, and especially the cryopreservation conditions, with the help of differential scanning calorimetry and zeta potential measurements. Five commonly used cryoprotective agents were evaluated (glucose, sucrose, trehalose, dextran, mannitol at 0, 5, 10, 20, and 30% [w/v]) after freeze-thawing and freeze-drying. The addition of carbohydrates led to a partial protection of the colloidal suspension, with leakage of 30% of itraconazole under the best cryopreservation conditions (10% of glucose or sucrose). Zeta potential measurements revealed that the main destabilization mechanism during freeze-drying was surface modifications of the nanospheres, and particularly drug desorption. Therefore, the hydrophilic surfactant adsorbed at the surface of the nanospheres played an important role in the cryopreservation. Replacing the commonly used non ionic surfactant PLURONIC®PE F68 by the anionic surfactant sodium deoxycholate resulted in a complete stabilization of itraconazole-loaded nanospheres after freeze-drying, with no drug desorption, in the presence of 10% sucrose, but not in the presence of glucose. As shown by thermal analysis, PLURONIC®PE F68 may crystallize during freezing, which could lead to surface modifications and drug desorption, whereas sodium deoxycholate may not. Moreover, the Tg′ of glucose-containing suspensions is 10°C lower than Tg′ of sucrose-containing suspensions, which may explain the shrinkage of the cake observed in the case of glucose and the homogeneous appearance of the dried product in the case of sucrose. © 1996 Wiley-Liss, Inc.     

RGD modified albumin nanospheres for tumour vasculature targeting

Objectives Cyclic arginine‐glycine‐aspartic acid (RGD) peptide‐anchored sterically stabilized albumin nanospheres (RGD‐SN) have been investigated for the selective and preferential presentation of carrier contents at angiogenic endothelial cells overexpressing a_vb₃ integrins on and around tumour tissue. Their targetabilty was assessed. Methods Albumin nanospheres were formulated, conjugated with RGD/RAD peptide and characterized on the basis of size and size distribution. The control Arginine‐Alanine‐Aspartic acid (RAD) peptide‐anchored sterically stabilized nanospheres (RAD‐SN) and nanosphere with 5 mol% PEG (SN) without peptide conjugate were used for comparison with RGD‐SN for in vitro cell binding, in vivo organ distribution and tumor angiogenesis studies. Key findings The average size of all nanospheres prepared was approximately 100 nm and maximum drug entrapment was 67.2 ± 5.2%. In‐vitro endothelial cell binding of nanospheres exhibited 8‐fold higher binding of RGD‐SN to human umbilical vein endothelial cells in comparison with the SN and RAD‐SN. RGD peptide‐anchored nanospheres were significantly (P ≤ 0.01) effective in the prevention of lung metastasis, angiogenesis and in effective regression of tumours compared with free fluorouracil, SN and RAD‐SN. Results indicated that cyclic RGD peptide‐anchored sterically stabilized nanospheres bearing fluorouracil were significantly (P ≤ 0.01) active against primary tumour and metastasis than the nontargeted sterically stabilized nanospheres and free drug. Conclusions Cyclic RGD peptide‐anchored sterically stabilized nanospheres appears promising for targeted cancer chemotherapeutics.     

抗人乳腺癌单克隆抗体偶联米托蒽醌白蛋白纳米球的初步研究

乳腺癌是危及女性生命健康最常见的恶性肿瘤,化疗是治疗乳腺癌的重要手段。但抗乳腺癌效果最好的阿霉素有效率也仅为37%[1],这与蒽环类抗肿瘤药物在乳腺中分布甚少有关。米托蒽醌对乳腺癌具有突出疗效,心脏毒性较小[2,3]。因此,本文将其作为模型药物制成白蛋白纳米球,再与抗人乳腺癌(抗ＣｅｒｂＢ2)单克隆抗体进行交联制成免疫纳米球。以提高药物对肿瘤细胞的选择性,达到提高疗效、降低毒副作用的目的。已有药物直接与单克隆抗体结合的研究报道[4],但未见将抗人乳腺癌单克隆抗体与载药纳米球交联的研究报道。仪器与药品Ｄ402Ｆ型电动搅拌机(…     

Nanoswimmers Based on Capped Janus Nanospheres

Nanoswimmers are synthetic nanoscale objects that convert the available surrounding free energy to a directed motion. For example, bacteria with various flagella types serve as textbook examples of the minuscule swimmers found in nature. Along these lines, a plethora of artificial hybrid and non-hybrid nanoswimmers have been introduced, and they could find many uses, e.g., for targeted drug delivery systems (TDDSs) and controlled drug treatments. Here, we discuss a certain class of nanoparticles, i.e., functional, capped Janus nanospheres that can be employed as nanoswimmers, their subclasses and properties, as well as their various implementations. A brief outlook is given on different fabrication and synthesis methods, as well as on the diverse compositions used to prepare nanoswimmers, with a focus on the particle types and materials suitable for biomedical applications. Several recent studies have shown remarkable success in achieving temporally and spatially controlled drug delivery in vitro using Janus-particle-based TDDSs. We believe that this review will serve as a concise introductory synopsis for the interested readers. Therefore, we hope that it will deepen the general understanding of nanoparticle behavior in biological matrices.     

庆大霉素-壳聚糖纳米涂层钛板的制备及系列研究

目的:制备负载庆大霉素-壳聚糖纳米粒的涂层钛板并对其表面形态?体外释药行为及抗金黄色葡萄球菌的性能进行评价?方法:采用溶剂铸膜(solvent casting)法制备庆大霉素-壳聚糖纳米涂层钛板,扫描电镜观察其表面形态,磷酸盐缓冲液中研究其体外释药行为,将庆大霉素-壳聚糖纳米涂层钛板置于均匀涂有1 × 108 CFU/ml金黄色葡萄球菌的Mueller-Hinton(MH)平板上连续培养直至抑菌环消失,以抑菌环直径为主要观察指标评价其在体外对金黄色葡萄球菌的抑制作用?结果:扫描电镜示庆大霉素-壳聚糖纳米粒较均匀地分布于钛板表面;体外释药行为显示庆大霉素-壳聚糖纳米涂层钛板中庆大霉素的释放可达到14 d,维持在52%左右;体外抑制金黄色葡萄球菌作用可维持9 d,抑菌环最大直径为(3.82 ± 0.03) cm?结论:制备的庆大霉素-壳聚糖纳米涂层钛板表面形态良好,体外释药稳定,对金黄色葡萄球菌有良好的抑制作用?     

羧基化聚乙烯基萘纳米微球的制备和应用

以乙烯基萘(VN)为聚合单体,采用乳液聚合法制备聚乙烯基萘(PVN)纳米微球。通过对其羧基化与β2微球蛋白(β2-M)抗体偶联,制成免疫检测试剂。分别用聚苯乙烯(PS)和 PVN 检测试剂测定β2-M 含量,数据经统计学处理和分析,对自制的 PVN 纳米微球胶乳增强免疫比浊( LE-TIA)检测试剂的性能进行评价。自制的羧基化 PVN 纳米微球免疫试剂成功对标准样本进行了检测并在一定范围内有较好的线性,比 PS 检测试剂更加灵敏。利用该研究采用的方法和条件可以成功制备粒径大小可控、单分散的羧基化PVN 纳米微球,是比 PS 更优的 LETIA 新载体,具有很好的临床应用前景。     

磁性二氧化硅纳米微球对人源脐带间充质干细胞活性的影响

目的 探究磁性二氧化硅纳米微球作为一种干细胞表面的潜在标记物,对人脐带间充质干细胞(umbilical cord mesenchymal stem cells,UCMSCs)的表面干性标志物表达、细胞增殖和迁移能力等生物学活性的影响.方法 先采用溶剂热法和St?ber方法制备一种生物相容性高的磁性二氧化硅纳米微球,再通...     

Modification of the Copolymers Poloxamer 407 and Poloxamine 908 can Affect the Physical and Biological Properties of Surface Modified Nanospheres

Purpose. To investigate the effects of the modification of the copolymers poloxamer 407 and poloxamine 908 on the physical and biological properties surface modified polystyrene nanospheres. Methods. A method to modify poloxamer 407 and poloxamine 908, introducing a terminal amine group to each PEO chain has been developed. The aminated copolymers can be subsequently radiolabelled with lodinated (I¹²⁵) Bolton-Hunter reagent. The aminated copolymers were used to surface modify polystyrene nanospheres. The physical and biological properties of the coated nanospheres were studied using particle size, zeta potential, in vitro non-parenchymal cell uptake and in vivo biodistribution experiments. Results. The presence of protonated amine groups in the modified copolymers significantly affected the physical and biological properties of the resulting nanospheres, although the effects were copolymer specific. The protonated surface amine groups in both copolymers reduced the negative zeta potential of the nanospheres. Acetylation of the copolymer's free amine groups resulted in the production of nanospheres with comparable physical properties to control unmodified copolymer coated nanospheres. In vivo, the protonated amine groups in the copolymers increased the removal of the nanospheres by the liver and spleen, although these effects were more pronounced with the modified poloxamer 407 coated nanospheres. Acetylation of the amine groups improved the blood circulation time of the nanospheres providing modified poloxamine 908 coated nanospheres with comparable biological properties to control poloxamine 908 coated nanospheres. Similarly, modified poloxamer 407 coated nanospheres had only slightly reduced circulation times in comparison to control nanospheres. Conclusions. The experiments have demonstrated the importance of copolymer structure on the biological properties of surface modified nanospheres. Modified copolymers, which possess comparable properties to their unmodified forms, could be used in nanosphere systems where antibody fragments can be attached to the copolymers, thereby producing nanospheres which target to specific body sites.