肿瘤热疗化疗联合治疗用温敏磁性复合粒子的磁热性能

采用无皂乳液聚合法制备了Fe₃O₄/P（N-异丙基丙烯酰胺-共-丙烯酰胺）[P（NIPAAm-co-Am）]温敏磁性复合粒子,分别采用透射电镜（TEM）,振动磁强仪（VSＭ）和动态激光散射仪（DLS）对复僵粒子进行表征,并着重研究了复合粒子在交变磁场作用下的磁热性能。结果表明,Fe₃O₄纳米粒子表面包裹了一层P（NIPAAm-co-Am）温敏性聚合物,其最低临界溶解温度（LCST）约为40℃,利用磁性粒子在交变磁场下的磁热性能可使复合粒子的温度升高至LCST以上,可触发复合粒子发生体积收缩。另外,复合粒子在交变磁场下的磁热性能可通过改变磁性粒子的浓度或调节磁场来调控。     

温敏聚合物/纳米CuS复合微球在肿瘤光热化学联合治疗中的应用

利用湿化学法合成了具有光热效应的纳米硫化铜(Cu S)颗粒,采用沉淀聚合法,以N-异丙基丙烯酰胺(NIPAAm)和N-乙烯基吡咯烷酮(NVP)为共聚单体,锂藻土(laponite)作为交联剂,吸附纳米硫化铜,制备出兼具光热效应和温敏响应性的复合微凝胶[P(NIPAAm-co-NVP)/Cu S](NNC/Cu S),并测试其载药和药物缓释性能.实验结果表明,制备的纳米Cu S和NNC/Cu S复合微凝胶均在近红外区有很宽的光谱吸收带,在980 nm(0.51 W/cm2)激光的辐照条件下,NNC/Cu S复合微凝胶具有良好的光热效应,温度在8 min内可以升至51.9℃,对于Hela细胞杀伤效果明显,并随着激光照射时间的延长效果越好.复合微凝胶的载药量为0.15mg/mg,在p H=5.5的PBS缓冲液中累积药物释放为75%,高于p H=7.4的63%.同时光热效应对于温敏性载药微球的药物释放具有有效地调控作用,在药物释放阶段,激光照射段药物释放率明显高于未加激光照射段.另外聚合物与纳米Cu S的复合改善了纳米Cu S对于细胞的毒性,NNC/Cu S复合微凝胶细胞存活率为90.9%高于纳米Cu S的63%.     

透明质酸修饰的介孔二氧化硅包覆金纳米棒的制备及在肿瘤化疗-热疗联合治疗中的应用

通过在包覆了金纳米棒的介孔硅表面修饰生物相容性的透明质酸, 得到了具有肿瘤靶向性的多功能药物载体. 实验结果表明, 透明质酸可以通过酰胺键修饰在介孔硅表面, 所得药物载体可在透明质酸酶作用下实现选择性释放. 该体系在近红外区域具有较高的吸收, 可以在近红外光照射下实现光热转换. 细胞实验结果表明, 该多功能药物载体可以有效靶向CD44过量表达的乳腺癌细胞, 通过CD44介导的内吞富集在肿瘤内部, 结合化学药物治疗和光热治疗, 显示出更高的肿瘤细胞凋亡效率.     

高性能、多功能化的磁性水凝胶材料的研究进展

以磁性纳米粒子为关键构件的磁性纳米复合水凝胶,拥有优良的机械性能、较好的生物相容性和丰富的磁性,因此在核磁成像、环境治理、热疗以及促进干细胞分化上有着显著的效果。基于目前的研究概况,本文简要介绍了纳米复合水凝胶的理化性质以及作为关键构件的磁性纳米粒子的特性以及制备方法,同时重点阐述了磁性水凝胶在应用及其设计策略方面的研究进展,并从应用角度出发提出了未来将会面临的挑战以及其发展趋势。     

用于卵巢癌化疗-光热联合治疗的吉西他滨/聚吡咯复合纳米粒子

利用铁离子诱发吡咯氧化聚合反应制备了尺寸均一的聚吡咯纳米粒子, 并进一步负载化疗药物吉西他滨, 得到了吉西他滨/聚吡咯复合纳米粒子. 该复合纳米粒子对吉西他滨的负载能力强, 在水溶液中的稳定性好, 有助于降低吉西他滨对正常组织的毒副作用. 此外, 该复合纳米粒子在近红外光区有较强的吸收, 能够将吸收的光能转化为热, 是一种良好的光热试剂, 具有光热治疗功能. 同时, 该复合纳米粒子能够在热刺激下释放吉西他滨, 具有光热介导的化疗功能. 因此, 吉西他滨/聚吡咯复合纳米粒子是一种兼具化疗和光热治疗功能的联合治疗试剂. 复合纳米粒子在808 nm近红外激光照射下能够快速提升系统温度, 实现光热治疗与化疗联合杀伤卵巢癌细胞, 具有良好的生物医学应用潜力.     

磁性无机-生物复合粒子敏感膜新型电流型免疫传感器的研究

合成了磁性Fe3O4纳米粒子,利用3-氨基丙基三乙氧基硅烷(APS)进行硅烷化,形成表面带有氨基的磁性Fe3O4纳米复合粒子,再用戊二醛将羊抗人免疫球蛋白G抗体(anti-IgG)固定在该磁性粒子表面,通过磁力将其修饰于固体石蜡碳糊电极表面制作成免疫传感器。与标记HRP的二抗体anti-IgG结合,以对苯二酚作为电子媒介体,实现对人免疫球蛋白G(IgG)的定量检测。IgG测定线性范围为2.5~400μg/L,检出限为0.75μg/L。该免疫传感器制作简单,成本低,表面更新方便,可用于临床血清检测。     

深冷状态下纳米镝铁氧体磁粒子磁性能的研究

采用湿化学法制备出稀土Dy3+掺杂的纳米Fe3O4磁粒子,用月桂酸进行了表面修饰,研究了磁粒子在室温和深冷(200.2～56.5 K)状态下的磁性能.经X射线衍射分析发现,适量的Dy3+掺杂不会改变纳米Fe3O4磁粒子的晶型结构.透射电镜(TEM)照片表明,制备出的纳米磁粒子成球性好,且大部分磁粒子的粒径在14 nm左右.通过磁性测量仪、振动样品磁强计(VSM)对磁性能进行了表征.磁化曲线表明掺杂引起磁性能发生变化,磁粒子室温下无剩磁和矫顽力,具有超顺磁性;深冷状态下出现剩磁和矫顽力,且随温度的降低,剩磁和矫顽力增大,不具有超顺磁性,饱和磁化强度略高于室温值.     

磁性二氧化硅复合纳米粒子的合成及其与青铜器的相互作用研究

采用反相微乳液法, 合成了以PVP分散的磁性Fe₃O₄纳米粒子为核、SiO₂为壳并复合有荧光标记物钌联吡啶的核壳型复合功能纳米粒子. 在对该功能型二氧化硅复合纳米粒子进行TEM、荧光特性和磁性等特性表征的基础上, 重点研究了水溶性高聚物PVP溶液对Fe₃O₄纳米粒子的分散性, 并将其均匀的包入SiO₂壳中, 基于此研究了该功能型二氧化硅复合纳米粒子与青铜器之间的相互作用、以功能型复合纳米粒子为材料对青铜器腐蚀机理进行了在线、无损、实时监测以及将复合纳米材料从被分析体系中无损去除的方法, 发展了适合于去除吸附于青铜器文物表面的功能型纳米粒子的新方法. 这一研究结果为以该纳米粒子为基质构建适合于青铜器表面成分分析的纳米传感器奠定了基础.     

磁性铁氧化物纳米粒子在药剂学上的应用

磁性铁氧化物纳米粒子（MIONPs）是近几十年发展起来的一种具有磁靶向性的纳米材料,其以良好的磁靶向性、小尺寸效应、生物相容性在生物医学领域具有很好的应用前景,尤其在药剂学领域的应用已经成为一个重要的研究热点。本文在总结近年来国内外有关多功能磁性铁氧化物纳米粒子研究成果的基础上,阐述了各种铁氧化物纳米粒子在药剂学领域的应用,主要是：MIONPs的智能载药靶向控释,MIONPs对特殊药物的靶向负载,MIONPs降低身体的多药耐药性（Multidrug resistance, MDR）,MIONPs加强药物治疗     

磁性铁氧化物纳米粒子在药剂学上的应用

磁性铁氧化物纳米粒子(MIONPs)是近几十年发展起来的一种具有磁靶向性的纳米材料,其以良好的磁靶向性、小尺寸效应、生物相容性等特点在生物医学领域具有很好的应用前景,尤其在药剂学领域的应用已经成为一个重要的研究方向。本文在总结近年来国内外有关多功能MIONPs研究成果的基础上,阐述了各种铁氧化物纳米粒子在药剂学领域的应用,主要包括MIONPs的智能载药靶向控释、对特殊药物的靶向负载、降低身体的多药耐药性(MDR)、加强药物治疗效果、载药穿透血脑屏障(BBB)等;并讨论了当前应用中的优点和不足。最后,展望了其在药物、药剂学领域的应用前景并指出了一些亟待解决的问题。     

Synthesis of Bilayer Surfactant-Coated Magnetic Nanoparticles for Application in Magnetic Fluid Hyperthermia

Nanocrystalline La_0.73Sr_0.27MnO₃ perovskite oxides with an average particle size of 26 nm were synthesized using the sol-gel method. To make water based magnetic fluid, the obtained nanoparticles were coated by self-organized bilayer surfactant containing oleic acid and sodium dodecyl sulfate as inner and outer layer, respectively. The bare and coated nanoparticles were characterized by x-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry, and transmission electron microscopy analyses. Calorimetric analysis was used to determine the heat generation efficiency of the prepared magnetic fluid under various alternating magnetic fields. The obtained results revealed that the maximum temperature achieved by the nanoparticles is in the therapeutic temperature range which enables these materials to be used as self-controlled heating agents in magnetic hyperthermia therapy.     

负载顺铂的泊洛沙姆温敏凝胶用于小鼠宫颈癌的局部化疗

为了探讨载有顺铂的温敏凝胶对小鼠宫颈癌的局部化疗作用,制备了载有顺铂的泊洛沙姆温敏凝胶,并通过流变学、体外溶蚀、体外释放等技术手段表征其结构和性能,采用鼠源宫颈癌U14细胞制备了原位宫颈/阴道癌模型,将载药凝胶灌注入荷瘤鼠阴道,评价载药凝胶对小鼠宫颈/阴道癌的抑制作用。结果表明,载有顺铂的泊洛沙姆温敏凝胶经阴道给药后对小鼠宫颈/阴道癌的抑瘤率可达到63.1%,可有效抑制小鼠宫颈癌的生长,而系统安全性则远远高于静脉注射顺铂。因此,载有顺铂的温敏凝胶有可能成为一种新型的宫颈癌治疗剂型。     

Thermosensitive Microparticles Based on Unsaturated Esters of some Poly- and Oligosaccharides: Preparation,Characterization, Drug Inclusion and Release

Summary: The paper concerns the preparation and characterization of hydrogel microparticles based on exopolysaccharide (Gellan, Xanthan) unsaturated derivatives and respectively on cyclodextrin as well as their application for some hydrosoluble and liposoluble drugs inclusion. In the first step the polysaccharide and cyclodextrin unsaturated esters (maleate, acrylate) were synthesized and their hydrogel forming capacity was tested using a grafting-crosslinking free-radical reaction with N-isopropyl acrylamide (NIPAm), at room temperature. For a better control of the crosslinking degree N,N' methylene-bis-acrylamide (BIS), replaced by cyclodextrin tri-acrylate (A-CD) in a few experiments, was used. The microparticles were obtained by using the method in w/o emulsion, in which the dispersed aqueous phase is the reaction mixture and the oil phase is hexane. The particles containing polysaccharide esters showed an average diameter around 100 µm when crosslinking was achieved with BIS. They were smaller than those crosslinked with A-CD, which are in the range of 200-300 µm; the particles based on Xanthan maleate were smaller than Gellan maleate based ones. Even much smaller particles (2-2.5 µm in diameter) were obtained by starting from A-CD grafted-crosslinked systems. The synthesized microparticles are able to include chloramphenicol, as well as progesterone; the drug is slowly released according to diffusion controlled kinetics. The application of these microparticles in emergency ophthalmic treatments is possible as a result of their thermal sensitivity; they can collapse and release the drug instantly when placed in contact with the human eye, at 37 °C.     

Tuning of Magnetic Hyperthermia Response in the Systems Containing Magnetosomes

A number of materials are studied in the field of magnetic hyperthermia. In general, the most promising ones appear to be iron oxide particle nanosystems. This is also indicated in some clinical trial studies where iron-based oxides were used. On the other hand, the type of material itself provides a number of variations on how to tune hyperthermia indicators. In this paper, magnetite nanoparticles in various forms were analyzed. The nanoparticles differed in the core size as well as in the form of their arrangement. The arrangement was determined by the nature of the surfactant. The individual particles were covered chemically by dextran; in the case of chain-like particles, they were encapsulated naturally in a lipid bilayer. It was shown that in the case of chain-like nanoparticles, except for relaxation, a contribution from magnetic hysteresis to the heating process also appears. The influence of the chosen methodology of magnetic field generation was also analyzed. In addition, the influence of the chosen methodology of magnetic field generation was analyzed. The application of a rotating magnetic field was shown to be more efficient in generating heat than the application of an alternating magnetic field. However, the degree of efficiency depended on the arrangement of the magnetite nanoparticles. The difference in the efficiency of the rotating magnetic field versus the alternating magnetic field was much more pronounced for individual nanoparticles (in the form of a magnetic fluid) than for systems containing chain nanoparticles (magnetosomes and a mix of magnetic fluid with magnetosomes in a ratio 1:1).     

Magnetic Hyperthermia Enhancement in Iron-based Materials Driven by Carbon Support Interactions

Magnetic hyperthermia (MH) shows great potential in clinical applications because of its very localized action and minimal side effects. Because of their high saturation magnetization values, reduced forms of iron are promising candidates for MH. However, they must be protected in order to overcome their toxicity and instability (i. e., oxidation) under biological conditions. In this work, a novel methodology for the protection of iron nanoparticles through confinement within graphitic carbon layers after thermal treatment of preformed nanoparticles supported on carbon is reported. We demonstrate that the size and composition of the nascent confined iron nanoparticles, as well as the thickness of their protective carbon layer can be controlled by selecting the nature of the carbon support. Our findings reveal that a higher nanoparticle–carbon interaction, mediated by the presence of oxygen-containing groups, induces the formation of small and well-protected α-Fe-based nanoparticles that exhibit promising results towards MH based on their enhanced specific absorption rate values.     

Thermosensitive Microneedles Capable of On Demand Insulin Release for Precise Diabetes Treatment

As a novel painless and minimally invasive transdermal drug delivery method, microneedles have solved the challenges of microbial infection and tissue necrosis associated with multiple subcutaneous injections in patients with diabetes. However, traditional soluble microneedles cannot switch drug release on and off according to the patient's needs during long-term use, which is one of the most critical elements of diabetes treatment. Herein, an insoluble thermosensitive microneedle (ITMN) that can control the release of insulin by adjusting the temperature, enabling the precise treatment of diabetes is designed. Thermosensitive microneedles are produced by in situ photopolymerization of the temperature-sensitive compound N-isopropylacrylamide with the hydrophilic monomer N-vinylpyrrolidone, which is encapsulated with insulin and bound to a mini-heating membrane. ITMN are demonstrated to have good mechanical strength and temperature sensitivity, can release significantly different insulin doses at different temperatures, and effectively regulate blood glucose in type I diabetic mice. Therefore, the ITMN provides a possibility for intelligent and convenient on-demand drug delivery for patients with diabetes, and when combined with blood glucose testing devices, it has the potential to form an integrated and precise closed-loop treatment for diabetes, which is of great importance in diabetes management.     

阳离子型温敏水凝胶的溶胀性能及其对表面活性剂的吸附行为

阳离子单体;温敏凝胶;阳离子型温敏水凝胶的溶胀性能及其对表面活性剂的吸附行为