趋磁细菌及磁小体在肿瘤治疗中的应用

提高抗肿瘤药物的靶向性是肿瘤治疗、降低药物副作用的重要手段。在肿瘤组织内部由于癌细胞的快速增殖致使其形成低氧区,低氧区会对多种肿瘤治疗方案产生耐受。趋磁细菌 (Magnetotactic bacteria, MTB) 是一类能在细胞内产生外包生物膜、纳米尺寸、单磁畴磁铁矿 (Fe3O4) 或硫铁矿 (Fe3S4) 晶体颗粒-磁小体的微生物的统称。在磁场的作用下,趋磁细菌可凭借鞭毛运动至厌氧区。趋磁细菌在动物体内毒性较低且生物相容性良好,其磁小体与人工合成的磁性纳米材料相比优势显著。文中在介绍趋磁细菌及其磁小体生物学特点、理化性能的基础上,综述了趋磁细菌作为载体偶联药物进入肿瘤内部,并通过感受低氧信号定位于肿瘤低氧区,以及趋磁细菌竞争肿瘤细胞铁源的研究进展,总结了磁小体运载化疗药物、抗体、DNA疫苗靶向结合肿瘤的研究进展,分析了趋磁细菌及磁小体肿瘤治疗中面临的问题,并对趋磁细菌和磁小体在肿瘤治疗中的应用进行了展望。     

Magnetoreception in microorganisms and fungi

The ability to respond to magnetic fields is ubiquitous among the five kingdoms of organisms. Apart from the mechanisms that are at work in bacterial magnetotaxis, none of the innumerable magnetobiological effects are as yet completely understood in terms of their underlying physical principles. Physical theories on magnetoreception, which draw on classical electrodynamics as well as on quantum electrodynamics, have greatly advanced during the past twenty years, and provide a basis for biological experimentation. This review places major emphasis on theories, and magnetobiological effects that occur in response to weak and moderate magnetic fields, and that are not related to magnetotaxis and magnetosomes. While knowledge relating to bacterial magnetotaxis has advanced considerably during the past 27 years, the biology of other magnetic effects has remained largely on a phenomenological level, a fact that is partly due to a lack of model organisms and model responses; and in great part also to the circumstance that the biological community at large takes little notice of the field, and in particular of the available physical theories. We review the known magnetobiological effects for bacteria, protists and fungi, and try to show how the variegated empirical material could be approached in the framework of the available physical models.     

磁杆菌HMB—1的磁小体特性及其合成条件的研究

从西安段家坡黄土剖面６１个土样中,分离纯化出一株磁杆菌ＨＭＢ１,并对其磁性特点及磁小体的合成条件进行了研究;同时用Ｘ射线能谱分析测定了磁小体的组成成分,主要为铁和钴。综合实验结果得出ＨＭＢ１生长及磁小体形成的最适培养基     

Preparation and anti-tumor efficiency evaluation of doxorubicin-loaded bacterial magnetosomes: magnetic nanoparticles as drug carriers isolated from Magnetospirillum gryphiswaldense

Bacterial magnetosomes (BMs) are commonly used as vehicles for certain enzymes, nucleic acids and antibodies, although they have never been considered drug carriers. To evaluate the clinical potential of BMs extracted from Magnetospirillum gryphiswaldense in cancer therapy, doxorubicin (DOX) was loaded onto the purified BMs at a ratio of 0.87 +/- 0.08 mg/mg using glutaraldehyde. The DOX-coupled BMs (DBMs) and BMs exhibited uniform sizes and morphology evaluated by TEM. The diameters of DBMs and BMs obtained by AFM were 71.02 +/- 6.73 and 34.93 +/- 8.24 nm, respectively. The DBMs released DOX slowly into serum and maintained at least 80% stability following 48 h of incubation. In vitro cytotoxic tests showed that the DBMs were cytotoxic to HL60 and EMT-6 cells, manifested as inhibition of cell proliferation and suppression in c-myc expression, consistent with DOX. These observations depicted in vitro antitumor property of DBMs similar to DOX. The approach of coupling DOX to magnetosomes may have clinical potential in anti-tumor drug delivery.     

Magnetotactic bacteria: nanodrivers of the future

Magnetotactic bacteria (MTB) represent a heterogeneous group of Gram-negative aquatic prokaryotes with a broad range of morphological types, including vibrioid, coccoid, rod and spirillum. MTBs possess the virtuosity to passively align and actively swim along the magnetic field. Magnetosomes are the trademark nano-ranged intracellular structures of MTB, which comprise magnetic iron-bearing inorganic crystals enveloped by an organic membrane, and are dedicated organelles for their magnetotactic lifestyle. Magnetosomes endue high and even dispersion in aqueous solutions compared with artificial magnetites, claiming them as paragon nanomaterials. MTB and magnetosomes offer high technological potential in modern science, technology and medicines. This review focuses on the applicability of MTB and magnetosomes in various areas of modern benefits.     

多细胞趋磁原核生物研究进展

多细胞趋磁原核生物指一类由含有磁小体的革兰氏阴性原核细胞聚集而成的球形或者卵球形细胞聚集体,一般由745个细胞组成,直径在223μm之间,它们可在地磁场或外加磁场中沿磁力线定位并做定向运动。通过对巴西潟湖、美国盐湖、德国和法国海岸带花瓣型MMPs以及最近对中国青岛海域潮间带菠萝型MMPs研究结果的总结,分别从MMPs的生物学特征、细胞内容物以及生态学分布及分类地位等方面的研究进行综述,并对未来研究方向进行一定的展望。     

趋磁细菌AMB-1生物矿化相关蛋白Mms6参与磁小体的合成

【目的】研究趋磁细菌AMB-1生物矿化相关蛋白Mms6与磁小体合成的关系。【方法】在液体静置培养条件和好氧条件下对AMB-1进行培养,分析基因mms6在不同培养条件下转录水平的变化;对基因mms6进行基因敲除,分析突变株的生长和产磁变化。【结果】基因mms6的转录水平随着磁小体的合成逐渐升高;mms6的突变导致菌株在液体静置培养条件下趋磁性降低约50%,但不会影响菌株的生长水平。【结论】基因mms6参与了趋磁细菌AMB-1胞内磁小体的合成。     

Magnetic Inclusions in Prokaryotic Cells

Prokaryotic cells may contain one of two types of magnetic intracellular structures, either crystalline magnetosomes or noncrystalline magnetic inclusions. In a magnetic field, the locomotor behavior of cells containing magnetosomes is categorized as magnetotaxis, whereas noncrystalline magnetic inclusions cause a passive attraction of cells containing such inclusions to a magnet. This review considers the distribution, structure, and function of both types of magnetic particles in prokaryotic cells.     

Effects of pulsed magnetic field on the formation of magnetosomes in the Magnetospirillum sp. strain AMB‐1

Magnetotactic bacteria are a diverse group of microorganisms which possess one or more chains of magnetosomes and are endowed with the ability to use geomagnetic fields for direction sensing, thus providing a simple and excellent model for the study of magnetite‐based magnetoreception. In this study, a 50 Hz, 2 mT pulsed magnetic field (PMF) was applied to study the effects on the formation of magnetosomes in Magnetospirillum sp. strain AMB‐1. The results showed that the cellular magnetism (R_mag) of AMB‐1 culture significantly increased while the growth of cells remained unaffected after exposure. The number of magnetic particles per cell was enhanced by about 15% and slightly increased ratios of magnetic particles of superparamagnetic property (size <20 nm) and mature magnetosomes (size >50 nm) were observed after exposure to PMF. In addition, the intracellular iron accumulation slightly increased after PMF exposure. Therefore, it was concluded that 50 Hz, 2 mT PMF enhances the formation of magnetosomes in Magnetospirillum sp. strain AMB‐1. Our results suggested that lower strength of PMF has no significant effects on the bacterial cell morphologies but could affect crystallization process of magnetosomes to some extent. Bioelectromagnetics 31:246–251, 2010. © 2009 Wiley‐Liss, Inc.