治疗癌症用的玻璃陶瓷

1前言长期以来，治疗癌症的方法是以切除病患部位的外科疗法为主。但是，多数器官一旦切除就不能再生。因此希望开发不切除患部，只杀死癌细胞，但又能促使正常细胞生长的治疗方法。作为这种方法，现在已采用的是化学疗法，免疫学疗法、放射疗法、温热疗法等。但是，尚未找到能不伤害正常细胞而只杀死癌细胞的有效抗癌剂，也没有研究出只对癌细胞产出有效抗体的方法。关于放射疗法和温热疗法，以往因为要从体外进行放射线照射和加热，这样就会伤害体表附近的正常组织，很难对体内深部的癌进行有效治疗。因此，最近在研究开发出理人肿瘤附近…     

溶胶-凝胶法制备铁磁性热种子材料

铁磁性微晶玻璃由于具有良好的磁性和生物活性,可以用来作为温热疗法治疗癌症的热种子材料。本文采用溶胶-凝胶法制备出SiO2-CaO-Fe2O3系基础铁磁性微晶玻璃,以及添加适量的Na2O、P2O5、FeO氧化物的铁磁性微晶玻璃。利用XRD测试样品中的晶相组成,采用VSM测试样品的磁性能数据。在模拟体液浸泡2-3周后,样品表面有羟基磷灰石层的形成,说明样品良好的生物活性。     

铁钙硅铁磁体微晶玻璃——一种治癌生物材料

扼要叙述温热疗法治疗癌症的原理,比较详尽地介绍了关于作为温热疗法热种子的铁钙硅铁磁体微晶玻璃的组成,形成过程,结构,磁性,生物相容性及癌症试验等方面研究的最新进展。     

钙铁硅铁磁体微晶玻璃生物活性的模拟体液研究

为了研究用作温热治疗肿瘤热种子材料的钙铁硅铁磁体微晶玻璃的生物活性，试样在模拟体液中浸泡以后，用ＳＥＭ、俄昂扬电子能谱、ＦＴ－ＩＲ对其表面生成的江膜进行观察和分析，研究结果表明，试样表面的硅胶层上生成物活性。     

高温及超高温热管的相容性和传热性能

对高温热管及超高温热管的相容性和实验件的传热性能进行了研究。提出了微电池腐蚀的机理,说明了材料、工质的选择匹配要求等相容性要求。设计、加工了钠高温热管及锂超高温热管,并对热管的传热特性进行了实验研究。高温及超高温热管工作时应注意要远离声速传热极限;超高温热管的传热极限结果表明,超高温热管应工作在更高的温度和更大的热通量。     

钙硅比对钙铁硅铁磁体微晶玻璃核化与晶化的影响

为了研制用作温热治疗癌症的铁磁体微晶玻璃热种子材料,制备了一组化学组成为40Fe2O3xCaO(60-x)SiO23B2O33P2O5玻璃(x=20、25、30、35质量分数),用XRD、DTA、VSM对其核化与晶化过程进行了研究.研究发现,钙铁硅微晶玻璃在还原气氛下热处理后,除了磁铁矿和硅灰石及少量赤铁矿晶相外,还会出现钙铁辉石、方石英晶相.钙硅比较小的玻璃,热处理温度-时间相图中钙铁辉石相区范围较大;钙硅比较大的,钙铁辉石相区范围较小.另外,钙硅比不同,玻璃的成核机理、开始析出磁铁矿的温度也不同.     

钙硅比对钙铁硅铁磁体微晶玻璃核化与晶化的影响

为了研制用作温热治疗癌症的铁磁体微晶玻璃热种子材料,制备了一组化学组成为40Fe2O3xCaO(60-x)SiO23B2O33P2O5玻璃(x=20、25、30、35质量分数),用XRD、DTA、VSM对其核化与晶化过程进行了研究.研究发现,钙铁硅微晶玻璃在还原气氛下热处理后,除了磁铁矿和硅灰石及少量赤铁矿晶相外,还会出现钙铁辉石、方石英晶相.钙硅比较小的玻璃,热处理温度-时间相图中钙铁辉石相区范围较大;钙硅比较大的,钙铁辉石相区范围较小.另外,钙硅比不同,玻璃的成核机理、开始析出磁铁矿的温度也不同.     

同时作为热种子和药物载体的生物陶瓷的研制

通过烧结法制作了LiFe5O8-CaO-SiO2-P2O5系统多孔磁性生物陶瓷,并对该陶瓷进行模拟体液浸泡、药物负载和缓释实验、XRD分析、孔径分析和磁性能的检测。实验结果表明,通过涂层的方法可以改善陶瓷样品的生物性能。有生物涂层样品的比饱和磁化强度和矫顽力分别能够达到28.1 A.m2.kg-1,2.39×103A.m-1,可以作为癌症温热疗法中使用的热种子,该多孔陶瓷同时表现出良好的药物载体功能。     

纳米尖晶石铁氧体在MgO-Al2O3-SiO2玻璃中的析晶研究

以正硅酸乙酯、醋酸镁、异丙醇铝、醋酸镍和硝酸铁为原料，通过溶胶一凝胶工艺合成了氧化镁一氧化铝一二氧化硅玻璃和微晶玻璃。采用DTA和XRD对凝胶玻璃的吸晶行为进行表征。DTA和XRD结果显示：凝胶体在500℃热处理后可以转变为透明玻璃体，在900℃热处理后，得到含有堇青石晶相的微晶玻璃；当5％(摩尔分数)氧化镍引入体系后，在800℃处理2h后，纳米尖晶石和堇青石同时从体系中析出；当氧化镍和三氧化二铁同时取代体系中的氧化镁和氧化铝时，纯纳米铁氧体尖晶石从玻璃体中析出。     

微晶玻璃建筑装饰材料现状与前景

介绍了作为建筑装饰材料的微晶玻璃的研究、产业化现状、存在问题及发展前景。     

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Compared to conventional hyperthermia that is limited by low selectivity and severe side effects,nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment.Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia,which introduces a new avenue,allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery,i.e.,long-lasting and/or systemic anti-tumor immunity.This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia.This includes the discussion about underlying mechanism such as immunogenic cell death,which initiates a profound immunological chain reaction.In order to propagate the immune activation as a viable therapeutic principle,we further discussed the tumor type-specific complexity in the immunological tumor microenvironment,including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.     

Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells

Ethanol has been shown to exhibit therapeutic properties as an ablative agent alone and in combination with thermal ablation. Ethanol may also increase sensitivity of cancer cells to certain physical and chemical antitumoral agents. The aim of our study was to assess the potential influence of nontoxic concentrations of ethanol on hyperthermia therapy, an antitumoral modality that is continuously growing and that can be combined with classical chemotherapy and radiotherapy to improve their efficiency. Human leukemia cells were included as a model in the study. The results indicated that ethanol augments the cytotoxicity of hyperthermia against U937 and HL60 cells. The therapeutic benefit of the hyperthermia/ethanol combination was associated with an increase in the percentage of apoptotic cells and activation of caspases-3, -8 and -9. Apoptosis triggered either by hyperthermia or hyperthermia/ethanol was almost completely abolished by a caspase-8 specific inhibitor, indicating that this caspase plays a main role in both conditions. The role of caspase-9 in hyperthermia treated cells acquired significance whether ethanol was present during hyperthermia since the alcohol enhanced Bid cleavage, translocation of Bax from cytosol to mitochondria, release of mitochondrial apoptogenic factors, and decreased of the levels of the anti-apoptotic factor myeloid cell leukemia-1 (Mcl-1). The enhancement effect of ethanol on hyperthermia-activated cell death was associated with a reduction in the expression of HSP70, a protein known to interfere in the activation of apoptosis at different stages. Collectively, our findings suggest that ethanol could be useful as an adjuvant in hyperthermia therapy for cancer.     

A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.     

Cisplatin-loaded carbon-encapsulated iron nanoparticles and their in vitro effects in magnetic fluid hyperthermia

Iron nanoparticles encapsulated by carbon are protected from reactions with their environment avoiding oxidation in ambient conditions and thus, preserving their magnetic properties. Such particles are good candidates for magnetic fluid hyperthermia. When graphite shells are present, acidic treatments allow the formation of carboxylic groups on the nanoparticle surface. Those carboxylic groups can be used for further complexation with the drug cisplatin. We show the possibility of loading cisplatin on such nanoparticles and that the loading is dependent on the degree of surface functionalization. The drug release is dependent on time and temperature, making it ideal for applications involving hyperthermia. We show the possibility of applying hyperthermia in vitro using these nanoparticles. When loaded with cisplatin a stronger cytotoxic effect is observed. Such particles could be potentially used as multimodal anti-cancer agents for therapies based on the synergistic effect of chemotherapy and hyperthermia.     

Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells

Osteosarcoma (OS) is a relatively rare form of cancer, but OS is the most commonly diagnosed bone cancer in children and adolescents. Chemotherapy has side effects and induces drug resistance in OS. Since an effective adjuvant therapy was insufficient for treating OS, researching novel and adequate remedies is critical. Hyperthermia can induce cell death in various cancer cells, and thus, in this study, we investigated the anticancer method of hyperthermia in human OS (U-2 OS) cells. Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells. Furthermore, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells. Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax. Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity. In addition, cells treated with calcium chelator (BAPTA-AM) blocked hyperthermia-induced cell apoptosis in U-2 OS cells. In conclusion, hyperthermia induced cell apoptosis substantially via the ROS, ER stress, mitochondria, and caspase pathways. Thus, hyperthermia may be a novel anticancer method for treating OS.     

Fabrication of a Novel Biocompatible Magnetic Biomaterial with Hyperthermia Potential

Preparation and characterization of a novel biocompatible magnetic biomaterial having hyperthermia potential is reported in this study. Fe³⁺ and Ni²⁺ (2:1) cosubstituted hydroxyapatite nanoparticles were synthesized by simple wet precipitation method followed by freeze‐drying which on heat treatment at 1150°C yielded the above mentioned biocompatible magnetic biomaterial composed of hydroxyapatite and β‐tricalcium phosphate along with nickel ferrite. The product was characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscope along with composition analysis. The magnetic behavior was analyzed by vibrating sample magnetometer and biocompatibility was assessed by testing the toxicity on Hela cells using MTT assay. The hyperthermia potential of the material was studied using induction heating. The prepared material has the potential to generate sufficient heat that could be easily controlled by magnetic field parameters and amount of sample. Hence, it can be a potential candidate for making implantable thermoseed for hyperthermia treatment.     

Study on Maximum Specific Loss Power in Fe3O4 Nanoparticles Decorated with Biocompatible Gamma-Cyclodextrins for Cancer Therapy with Superparamagnetic Hyperthermia

Different chemical agents are used for the biocompatibility and/or functionality of the nanoparticles used in magnetic hyperthermia to reduce or even eliminate cellular toxicity and to limit the interaction between them (van der Waals and magnetic dipolar interactions), with highly beneficial effects on the efficiency of magnetic hyperthermia in cancer therapy. In this paper we propose an innovative strategy for the biocompatibility of these nanoparticles using gamma-cyclodextrins (γ-CDs) to decorate the surface of magnetite (Fe₃O₄) nanoparticles. The influence of the biocompatible organic layer of cyclodextrins, from the surface of Fe₃O₄ ferrimagnetic nanoparticles, on the maximum specific loss power in superparamagnetic hyperthermia, is presented and analyzed in detail in this paper. Furthermore, our study shows the optimum conditions in which the magnetic nanoparticles covered with gamma-cyclodextrin (Fe₃O₄–γ-CDs) can be utilized in superparamagnetic hyperthermia for an alternative cancer therapy with higher efficiency in destroying tumoral cells and eliminating cellular toxicity.     

Ischemia-Reperfusion under Hyperthermia Increases Heme Oxygenase-1 in Pyramidal Neurons and Astrocytes with Accelerating Neuronal Loss in Gerbil Hippocampus

It has been studied that the damage or death of neurons in the hippocampus is different according to hippocampal subregions, cornu ammonis 1–3 (CA1–3), after transient ischemia in the forebrain, showing that pyramidal neurons located in the subfield CA1 (CA1) are most vulnerable to this ischemia. Hyperthermia is a proven risk factor for brain ischemia and can develop more severe and extensive brain damage related with mortality rate. It is well known that heme oxygenase-1 (HO-1) activity and expression is increased by various stimuli in the brain, including hyperthermia. HO-1 can be either protective or deleterious in the central nervous system, and its roles depend on the expression levels of enzymes. In this study, we investigated the effects of hyperthermia during ischemia on HO-1 expression and neuronal damage/death in the hippocampus to examine the relationship between HO-1 and neuronal damage/death following 5-min transient ischemia in the forebrain using gerbils. Gerbils were assigned to four groups: (1) sham-operated gerbils with normothermia (Normo + sham group); (2) ischemia-operated gerbils with normothermia (Normo + ischemia group); (3) sham-operated gerbils with hyperthermia (39.5 ± 0.2 °C) during ischemia (Hyper + sham group); and (4) ischemia-operated gerbils with hyperthermia during ischemia (Hyper + ischemia group). HO-1 expression levels in CA1–3 of the Hyper + ischemia group were significantly higher than those in the Normo + ischemia group. HO-1 immunoreactivity in the Hyper + ischemia group was significantly increased in pyramidal neurons and astrocytes with time after ischemia, and the immunoreactivity was significantly higher than that in the Normo + ischemia group. In the Normo + Ischemia group, neuronal death was shown in pyramidal neurons located only in CA1 at 5 days after ischemia. However, in the Hyper + ischemia group, pyramidal neuronal death occurred in CA1–3 at 2 days after ischemia. Taken together, our findings showed that brain ischemic insult during hyperthermic condition brings up earlier and severer neuronal damage/death in the hippocampus, showing that HO-1 expression in neurons and astrocytes is different according to brain subregions and temperature condition. Based on these findings, we suggest that hyperthermia in patients with ischemic stroke must be taken into the consideration in the therapy.     

Acid‐sensitive magnetic nanoparticles as potential drug depots

Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH‐sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Because of the released drug, the particles were found to be cytotoxic to human breast cancer cells in vitro. Such magnetic nanoparticles, with the potential to retain drug under physiological conditions and release the drug in conditions where the pH is lower or temperature is higher, may be useful in magnetic drug targeting by reducing the side effects of the drug caused to healthy tissues. In addition, they may serve as hyperthermia agents where the high temperatures used in hyperthermia can trigger further drug release. © 2010 American Institute of Chemical Engineers AIChE J, 2011