Magnetic microspheres for targeting of drugs

Magnetic microspheres were prepared from starch. The microspheres could be crosslinked with various agents, and drugs could be entrapped adsorbed, or covalently coupled to the microspheres.     

药物磁靶向定位释放模拟装置的设计与应用

采用蠕动泵、钕铁硼永磁铁、聚乙烯管、恒温水浴锅和玻璃管组装了一种模拟人体血液循环的磁靶向装置,并应用于模型磁性载药粒子Fe3O4@DFUR-LDH（DFUR：去氧氟尿苷;LDH：硝酸根插层水滑石）的磁靶向定位和药物释放性能的分析。 研究发现,该装置对磁性载药粒子的滞留量最高可达85.3%,并随载药粒子与磁场的间距增大而减小,随释放介质的流速增大而减小。 而装置中模型磁性载药粒子的药物释放速率随释放介质的流速增大而增大。 同时,通过修改该装置的管路系统模拟了药物在治疗过程中不断被消耗情形下的磁靶向治疗过程。 该装置不但可以实现磁性载药粒子的滞留,还可以分析磁性载药粒子被滞留后的定位释放行为,是磁性载药粒子临床试验前性能分析测试的有效工具。     

Magnetic Helical Micromachines

Helical microrobots have the potential to be used in a variety of application areas, such as in medical procedures, cell biology, or lab‐on‐a‐chip. They are powered and steered wirelessly using low‐strength rotating magnetic fields. The helical shape of the device allows propulsion through numerous types of materials and fluids, from tissue to different types of bodily fluids. Helical propulsion is suitable for pipe flow conditions or for 3D swimming in open fluidic environments.     

Pt(II) complexes immobilized on polymer‐modified magnetic carbon nanotubes as a new platinum drug delivery system

We combine nanotechnology and chemical synthesis to create a novel multifunctional platinum drug delivery vehicle based on magnetic carbon nanotubes (multiwall carbon nanotubes/Fe₃O₄@poly(citric acid)/cis‐[(Pt(1,7‐phenanthroline)(DMSO)Cl₂)]‐b‐poly(ethylene glycol) (MCNTs/FO@PC/Pt(II)‐b‐PEG)) for targeted cancer therapy. MCNTs/FO@PC/Pt(II)‐b‐PEG was conveniently prepared by conjugating cis‐[Pt(1,7‐phenanthroline)(DMSO)Cl₂] complex to MCNTs/FO@PC‐b‐PEG via strong hydrogen‐bonding interactions. In comparison with free cisplatin and Pt(II) complex, MCNTs/FO@PC/Pt(II)‐b‐PEG shows higher solubility in aqueous solution and higher cytotoxicity towards human cervical cancer HeLa cells and human breast cancer MDA‐MB‐231 cells. In vitro release experiments revealed that the platinum drug‐loaded delivery system is relatively stable under physiological conditions (pH = 7.4 and 37 °C) but susceptible to acidic environments (pH = 5.6 and 37 °C) which would trigger the release of loaded drugs. Fluorescence microscopy studies revealed that this magnetic nanohybrid system possesses marked cell‐specific targeting in vitro in the presence of an external magnetic field. The results indicated that the prepared superparamagnetic MCNTs/FO@PC/Pt(II)‐b‐PEG nanohybrid system is a promising candidate for inhibiting the proliferation of cancer cells.     

Control of Drug Release through the In Situ Assembly of Stimuli‐Responsive Ordered Mesoporous Silica with Magnetic Particles

A site‐selective controlled delivery system for controlled drug release is fabricated through the in situ assembly of stimuli‐responsive ordered SBA‐15 and magnetic particles. This approach is based on the formation of ordered mesoporous silica with magnetic particles formed from Fe(CO)₅ via the surfactant‐template sol‐gel method and control of transport through polymerization of N‐isopropyl acrylamide inside the pores. Hydrophobic Fe(CO)₅ acts as a swelling agent as well as being the source of the magnetic particles. The obtained system demonstrates a high pore diameter (7.1 nm) and pore volume (0.41 cm³ g^?1), which improves drug storage for relatively large molecules. Controlled drug release through the porous network is demonstrated by measuring the uptake and release of ibuprofen (IBU). The delivery system displays a high IBU storage capacity of 71.5 wt %, which is almost twice as large as the highest value based on SBA‐15 ever reported. In vitro testing of IBU loading and release exhibits a pronounced transition at around 32 °C, indicating a typical thermosensitive controlled release.     

药物配体与生物大分子受体相互作用核磁共振的研究进展

药物与生物体内目标大分子之间的相互作用,是决定药物药理活性和代谢稳定性的主要因素。如何快速高效地识别出能与靶分子相互作用且能抑制其体外活性的药物分子,是制药工业普遍关注的问题。核磁共振已经成为研究小分子配体和生物大分子相互作用的一种非常重要的手段。检测小分子配体信号在作用过程中的变化以识别药物分子,是核磁共振进行药物筛选的主要方法之一。本文介绍了近年来这方面的研究进展。     

All‐in‐One Target‐Cell‐Specific Magnetic Nanoparticles for Simultaneous Molecular Imaging and siRNA Delivery

Cancer‐cell‐targeted gene silencing was observed with a magnetic‐nanoparticle platform (MEIO, magnetism‐engineered iron oxide) on which a fluorescent dye, siRNA, and a RGD‐peptide targeting moiety were attached (see picture). The different functionalities enable the macroscopic (magnetic resonance) and microscopic (fluorescence) imaging of target cells. This system may be suitable for concurrent diagnostic and therapeutic applications.

     

羧甲基壳聚糖磁性纳米粒子的合成及应用

通过合成油酸修饰的Fe3O4纳米粒子和羧甲基壳聚糖直接包埋油酸修饰的Fe3O4纳米粒子的两步合成法制备了羧甲基壳聚糖磁性纳米粒子。采用透射电子显微镜、傅里叶变换红外光谱、振动样品磁强计和同步热分析测试技术对制备的羧甲基壳聚糖磁性纳米粒子进行了表征。所得磁性纳米粒子呈规则球形,粒径约为10 nm;表面含羧基,且具有很好的顺磁性和稳定性。考察了羧甲基壳聚糖磁性纳米粒子对阿霉素的载药量和对阿霉素在磷酸盐缓冲溶液中的缓释性能。结果表明,磁性纳米粒子对阿霉素展示了较高的载药量(91.8 mg/g),结合了阿霉素的磁性复合物对阿霉素的缓释作用明显,说明制备的羧甲基壳聚糖磁性纳米粒子有望作为治疗肿瘤的纳米磁靶向药物输送载体。     

Preparation of bamboo-derived magnetic biochar for solid-phase microextraction of fentanyls from urine

In this study, a biochar-based magnetic solid-phase microextraction method, coupled with liquid chromatography–mass spectrometry, was developed for analyzing fentanyl analogs from urine sample. Magnetic biochar was fabricated through a one-step pyrolysis carbonization and magnetization process, followed by an alkali treatment. In order to achieve desired extraction efficiency, feed stocks (wood and bamboo) and different pyrolysis temperatures (300–700°C) were optimized. The magnetic bamboo biochar pyrolyzed at 400°C was found to have the greatest potential for extraction of fentanyls, with enrichment factors ranging from 58.9 to 93.7, presumably due to H-bonding and π–π interactions between biochar and fentanyls. Various extraction parameters, such as type and volume of desorption solvent, pH, and extraction time, were optimized, respectively, to achieve the highest extraction efficiency for the target fentanyls. Under optimized conditions, the developed method was found to have detection limits of 3.0–9.4 ng/L, a linear range of 0.05–10 μg/L, good precisions (1.9–9.4% for intrabatch, 2.9–9.9% for interbatch), and satisfactory recoveries (82.0–111.3%). The developed method by using magnetic bamboo biochar as adsorbent exhibited to be an efficient and promising pretreatment procedure and could potentially be applied for drug analysis in biological samples.     

磁性壳聚糖微球的制备、表征及其靶向给药研究

磁性微球;阿司匹林;磁性壳聚糖微球的制备、表征及其靶向给药研究     

Enhancing Tumor Cell Response to Chemotherapy through the Targeted Delivery of Platinum Drugs Mediated by Highly Stable,Multifunctional Carboxymethylcellulose‐Coated Magnetic Nanoparticles

The fabrication of nanoparticles using different formulations, and which can be used for the delivery of chemotherapeutics, has recently attracted considerable attention. We describe herein an innovative approach that may ultimately allow for the selective delivery of anticancer drugs to tumor cells by using an external magnet. A conventional antitumor drug, cisplatin, has been incorporated into new carboxymethylcellulose‐stabilized magnetite nanoparticles conjugated with the fluorescent marker Alexa Fluor 488 or folic acid as targeting agent. The magnetic nanocarriers possess exceptionally high biocompatibility and colloidal stability. These cisplatin‐loaded nanoparticles overcome the resistance mechanisms typical of free cisplatin. Moreover, experiments aimed at the localization of the nanoparticles driven by an external magnet in a medium that mimics physiological conditions confirmed that this localization can inhibit tumor cell growth site‐specifically.     

Magnetoliposomes as Potential Carriers of Doxorubicin to Tumours

Studies on magnetoliposomes (MLUV) as potential carriers for magnetic‐field‐dependent drug delivery are presented. The systems were formed with hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) confined within the bilayer of the liposomes. The nanomechanical properties of bilayer lipid membranes were evaluated and related to the amount of incorporated SPIONs. It was found that the presence of SPIONs in the lipid membrane leads to overall stiffening and increases morphological inhomogeneity, facilitating rupture of the MLUV membrane in a low‐frequency alternating magnetic field (AMF). To verify the findings, doxorubicin release from MLUVs in the presence and absence of an AMF was measured. Under experimental conditions, drug release proceeds through MLUV rupture induced by mechanical vibration of SPIONs rather than through localized heating in the vicinity of the SPIONs.     

Biocompatible and biodegradable polymer nanofibers displaying superparamagnetic properties.

Superparamagnetic polymer nanofibers intended for drug delivery and therapy are considered here. Magnetite (Fe3O4) nanoparticles in the diameter range of 5-10 nm were synthesized in aqueous solution. Polymer nanofibers containing magnetite nanoparticles were prepared from commercially available poly(hydroxyethyl methacrylate), PHEMA, and poly-L-lactide (PLLA) by the electrospinning technique. Nanofibers with diameters ranging from 50 to 300 nm were obtained. Nanofibers containing up to 35 wt % magnetite nanoparticles displayed superparamagnetism at room temperature. The blocking temperature was about 50 K for an applied field of 500 Oe, and the saturation magnetization was 3.5 emu g(-1) and 1.1 emu g(-1) for Fe3O4/PHEMA and Fe3O4/PLLA nanofibers, respectively, and depended on the amount of Fe3O4 nanoparticles in the nanocomposites. To test such magnetic nano-objects for applications as drug carriers and drug-release systems we incorporated a fluorescent albumin with dog fluorescein isothiocyanate (ADFI).     

Fe3O4@mMoO3介孔多功能纳米载体的制备及其微波响应药物传递

以氨基功能化的Fe_3O_4纳米颗粒为磁核,结合直接沉淀法和模板法在其表面包覆上介孔MoO_3层,制备磁性-微波热转换性-介孔结构于一体的多功能核-壳结构复合纳米载体Fe_3O_4@mMoO_3,并对其结构、载药及微波控制靶向给药性进行研究。TEM图表明所得的复合纳米载体具有明显的核壳结构,完美的球形,且壳层中有清晰的孔状结构。磁性和微波热转换特性分析表明,该复合载体兼具良好的磁性和微波热转换特性,可实现药物的靶向可控给药。以布洛芬(IBU)为模型药物,对该复合纳米载体的药物负载能力和微波响应可控释放性进行研究,结果表明,在持续微波辐射90 s时IBU的释放率达到90%,远远高于仅搅拌时的释放率。     

Covalent bonding of magnetic Fe3O4 nanoparticles to aminopropyl‐functionalized magnesium phyllosilicate clay: Synthesis and cytotoxic potential investigation

Stable water dispersion of Fe₃O₄ magnetic nanoparticles (NPs) were successfully synthesized by using 3‐glycidoxypropyltrimethoxysilane (GPTMS) and Mg‐phyllo (organo) silicate known as aminoclay (AC) containing pendant amino groups with the approximate composition (R₈Si₈Mg₆O₁₆(OH)₄, R = CH₂CH₂CH₂NH₂). The Fe₃O₄‐GPTMS magnetic NPs with an epoxy functional group are suitable for forming a covalent bond with the amine group of aminoclay in an epoxy ring opening reaction. Appropriate Fe₃O₄‐GPTMS‐aminoclay (FG‐AC) magnetic composite are promising carriers for the targeting and delivery of platinum‐based anticancer drugs. Analysis of the cytotoxicity of the nanostructures on a K562 leukemia cell line using a colorimetery assay shows that both the FG‐AC and cis‐platin/FG‐AC magnetic composite were biocompatible. The nanostructures characterizations were investigated by Fourier transform infrared spectroscopy, X‐ray diffraction, transmission electron microscopy and energy dispersive analysis of X‐ray techniques. Magnetic measurement revealed that the saturated magnetization of the FG‐AC nanocomposite reached 7.6 emu/g and showed the characteristics of magnetism.     

单分散磁性纳米粒子靶向药物载体

本文综述了单分散磁性氧化铁纳米粒子的主要制备方法、表面修饰以及在生物医学靶向药物方面的应用研究进展。金属有机前驱体高温热分解法、溶剂热合成法和LSS（liquid-solid-solution）法是目前制备高质量单分散磁性纳米粒子比较有效的手段。通过表面修饰制备出的具有良好水溶性、生物相容性和活性功能基团的磁靶向药物载体将可能实现定位蓄积、高效载药、控制释药和可生物降解等靶向治疗癌症的目的。开发出具有荧光检测、主动靶向识别、高效载药、智能控药释放、无毒副作用和生物相容性于一体的多功能靶向药物载体将是其发展趋势。     

磁应答型药物递送载体的设计与构建

复合磁性生物材料的发展和应用已引起生物医学领域的极大关注。磁性纳米粒子因其易功能化而具有靶向药物传递、可控药物释放及磁成像特性逐渐成为药物传递和新型诊疗领域最有前途的材料之一。基于磁性纳米粒子或掺杂的铁氧化物构建的远程触发磁性载药递送系统,有望实现在运输过程中携载药物不泄露的情况下,提高药物递送效率且对病灶周围的健康细胞无毒或低毒性。为构建理想的可控靶向磁性药物递送系统,多种材料或配体可以与磁性纳米粒子复合来构建更安全有效的磁性药物递送系统。一些生物分子、聚合物及天然产物等通过与磁性纳米粒子相结合,构建出可用于药物传递且具有独特性质的磁性复合新材料。迄今为止,具有磁场应答能力的磁性药物递送载体已经在远程控制药物释放领域得到了长足发展。本文总结了近年来磁性药物递送载体作为远程控制治疗体系在设计与构建上的研究进展。重点关注了磷脂分子、聚合物、多孔微纳米材料以及天然产物等与其构建的复合材料,并对当前磁性复合特定给药载体的优点、局限及发展前景等做了简要阐述。