磁小体介导的生物传感器研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2018-0223

摘要/Abstract

摘要： 磁小体（Bacterial magnetosomes,BMs）是由趋磁细菌（Magnetotactic bacteria,MTB）合成的用于在其水生栖息地中进行地磁导航的专用细胞器,由外部的脂质双层膜和内部的磁性纳米晶体组成。其具有粒径分布窄、形态均匀、单磁畴、顺磁性、比表面积大及生物相容性高等特点被广泛应用于医疗领域,可作为抗癌药物的递送载体、核磁共振成像对比剂和成像探针等。目前,基于BMs制备生物传感器并应用于生物检测技术领域的研究相对较少,且主要偏向于在BMs膜的表面共价或非共价修饰上抗体,利用抗原抗体之间的特异性免疫反应来实现靶物质的检测。综述了BMs的结构和组成、基本特性、提取和纯化、形态结构表征及其在靶物质富集方面的应用,并着重介绍了几类以BMs为基础的生物传感器如电化学生物传感器、荧光生物传感器、磁生物传感器等,讨论了磁小体介导的生物传感器在应用研究中的实际意义及其存在的问题。展望了磁小体介导的生物传感器的发展前景,面临的机遇及挑战,以期为促进磁小体介导的生物传感器的实际应用提供参考。

关键词: 磁小体, 纳米材料, 生物传感器, 富集

Abstract: Bacterial magnetosomes（BMs）are special organelles synthesized by magnetotactic bacteria（MTB）and used for geomagnetic navigation in their aquatic habitat. It consists of an external lipid bilayer membrane and internal magnetic nanocrystals. Because of its narrow particle size distribution,uniform morphology,single magnetic domain,paramagnetism,large specific surface area,and high biocompatibility,it is widely used in the medical field as an anticancer drug delivery vehicle,nuclear magnetic resonance imaging contrast agent and imaging probe,etc. At present,there are relatively few researches on the preparation of biosensors based on BMs and applied in the biological detection technology field,and they are mainly biased toward the covalent or non-covalent modification of antibodies on the surface of BMs membranes,and the use of antigen-antibody-specific immunoreactions to achieve the detection of target substances. This article reviews the structure and composition,basic characteristics,extraction and purification,morphological structure characterization and application of BMs in the enrichment of target substances,and highlights several types of BMs-based biosensors such as electrochemical biosensors,fluorescent biosensors,magnetic biosensors,etc. Finally,the practical significance and existing problems of magnetosome-mediated biosensors in application research are discussed. The prospects for the development of magnetosome-mediated biosensors and the opportunities and challenges that may be faced are anticipated in order to provide reference for promoting the application of magnetosome-mediated biosensors in practice.

Key words: magnetosomes, nanomaterials, biosensors, enrichment

李舒婷, 周子琦, 田杰生, 许文涛. 磁小体介导的生物传感器研究进展[J]. 生物技术通报, 2018, 34(9): 70-78.

LI Shu-ting, ZHOU Zi-qi, TIAN Jie-sheng, XU Wen-tao. Research Progress on Magnetosome-mediated Biosensors[J]. Biotechnology Bulletin, 2018, 34(9): 70-78.

参考文献

[1] Faivre D, Schuler D.Magnetotactic bacteria and magnetosomes[J]. Chem Rev, 2008, 108(11):4875-4898.
[2] Jacob JJ, Suthindhiran K.Magnetotactic bacteria and magnetosomes-Scope and challenges[J]. Materials Science and Engineering:C, 2016, 68:919-928.
[3] Erdal E, Demirbilek M, Yeh Y, et al.A Comparative study of receptor-targeted magnetosome and HSA-coated iron oxide nanoparticles as MRI contrast-enhancing agent in animal cancer model[J]. Appl Biochem Biotechnol, 2018, 185(1):91-113.
[4] Sun J, Li Y, Liang XJ, et al.Bacterial magnetosome:a novel biogenetic magnetic targeted drug carrier with potential multifunctions[J]. J Nanomater, 2011(2011):469031-469043.
[5] Alphandéry E.Applications of magnetosomes synthesized by magnetotactic bacteria in medicine[J]. Frontiers in Bioengineering and Biotechnology, 2014, 2:5.
[6] Ceyhan B, Alhorn P, Lang C, et al.Semisynthetic biogenic magnetosome nanoparticles for the detection of proteins and nucleic acids[J]. Small, 2006, 2(11):1251-1255.
[7] Chen JF, Li Y, Wang ZF, et al.High-sensitivity detection of fruit tree viruses using bacterial magnetic particles[J]. Journal of Integrative Plant Biology, 2009, 51(4):409-413.
[8] Xiang Z, Yang X, Xu J, et al.Tumor detection using magnetosome nanoparticles functionalized with a newly screened EGFR/HER2 targeting peptide[J]. Biomaterials, 2017, 115:53-64.
[9] Boucher M, Geffroy F, Prévéral S, et al.Genetically tailored magnetosomes used as MRI probe for molecular imaging of brain tumor[J]. Biomaterials, 2017, 121:167-178.
[10] Alphandéry E, Guyot F, Chebbi I.Preparation of chains of magnetosomes, isolated from Magnetospirillum magneticum strain AMB-1 magnetotactic bacteria, yielding efficient treatment of tumors using magnetic hyperthermia[J]. International Journal of Pharmaceutics, 2012, 434(1-2):444-452.
[11] Lins U, Freitas F, Keim CN, et al.Electron spectroscopic imaging of magnetotactic bacteria:magnetosome morphology and diversity[J]. Microscopy and Microanalysis, 2000, 6(5):463-470.
[12] Grünberg K, Müller EC, Otto A, et al.Biochemical and proteomic analysis of the magnetosome membrane in Magnetospirillum gryphiswaldense[J]. Applied and Environmental Microbiology, 2004, 70(2):1040-1050.
[13] Nakamura N, Burgess JG, Yagiuda K, et al.Detection and removal of Escherichia coli using fluorescein isothiocyanate conjugated monoclonal antibody immobilized on bacterial magnetic particles[J]. Anal Chem, 1993, 65(15):2036-2039.
[14] Xu J, Hu J, Liu L, et al.Surface expression of protein A on magnetosomes and capture of pathogenic bacteria by magnetosome/antibody complexes[J]. Frontiers in Microbiology, 2014, 5:136.
[15] 刘珺, 周培国. 趋磁细菌应用于重金属废水处理的研究进展[J]. 环境科技, 2008, 21(6):60-63.
[16] Li K, Chen C, Chen C, et al.Magnetosomes extracted from Magnetospirillum magneticum strain AMB-1 showed enhanced peroxidase-like activity under visible-light irradiation[J]. Enzyme and Microbial Technology, 2015, 72:72-78.
[17] Xiang L, Wei J, Jianbo S, et al.Purified and sterilized magnetosomes from Magnetospirillum gryphiswaldense MSR-1 were not toxic to mouse fibroblasts in vitro[J]. Letters in Applied Microbiology, 2007, 45(1):75-81.
[18] Sun J, Tang T, Duan J, et al.Biocompatibility of bacterial magnet-osomes:acute toxicity, immunotoxicity and cytotoxicity[J]. Nanotoxicology, 2010, 4(3):271-283.
[19] Revathy T, Jayasri MA, Suthindhiran K.Toxicity assessment of magnetosomes in different models[J]. 3 Biotech, 2017, 7(2):126.
[20] Guo F, Liu Y, Chen Y, et al.A novel rapid and continuous procedure for large-scale purification of magnetosomes from Magnetospirillum gryphiswaldense[J]. Applied Microbiology and Biotechnology, 2011, 90(4):1277-1283.
[21] Pi F, Sun J, Liu W, et al.Elimination of aflatoxin B1 in vegetable oil based on immuno-magnetosomes probes from a novel magnetotactic bacterium[J]. Food Control, 2017, 80:319-326.
[22] Wu L, Gao B, Zhang F, et al.A novel electrochemical immunosen-sor based on magnetosomes for detection of staphylococcal enterotoxin B in milk[J]. Talanta, 2013, 106:360-366.
[23] Mann S, Moench TT, Williams RJP.A high resolution electron microscopic investigation of bacterial magnetite. implications for crystal growth[J]. Proceedings of the Royal Society of London, 1984, 221(1225):385-393.
[24] Feng S, Wang L, Palo P, et al.Integrated self-assembly of the Mms6 magnetosome protein to form an iron-responsive structure[J]. International Journal of Molecular Sciences, 2013, 14(7):14594-606.
[25] Yamamoto D, Taoka A, Uchihashi T, et al.Visualization and structural analysis of the bacterial magnetic organelle magnetosome using atomic force microscopy[J]. Proc Natl Acad Sci, 2010, 107(20):9382-9387.
[26] Li A, Zhang H, Zhang X, et al.Rapid separation and immunoassay for low levels of Salmonella in foods using magnetosome-antibody complex and real-time fluorescence quantitative PCR[J]. Journal of Separation Science, 2010, 33(21):3437-3443.
[27] Huang J, Guo L, Zheng L M.Rapid enrichment and determination of phosphopeptides using bacterial magnetic particles via both strong and weak interactions[J]. Analyst, 2010, 135(3):559-563.
[28] Xiong K, Wei W, Jin Y, et al.Biomimetic immuno-magnetosomes for high-performance enrichment of circulating tumor cells[J]. Adv Mater, 2016, 28(36):7929-7935.
[29] Ota H, Takeyama H, Nakayama H, et al.SNP detection in transforming growth factor-β1 gene using bacterial magnetic particles[J]. Biosens Bioelectron, 2003, 18(5-6):683-687.
[30] Amemiya Y, Tanaka T, Yoza B, et al.Novel detection system for biomolecules using nano-sized bacterial magnetic particles and magnetic force microscopy[J]. J Biotechnol, 2005, 120(3):308-314.
[31] Sun X, Wu L, Ji J, et al.Longitudinal surface plasmon resonance assay enhanced by magnetosomes for simultaneous detection of Pefloxacin and Microcystin-LR in seafoods[J]. Biosens Bioelectron, 2013, 47:318-323.
[32] Wacker R, Ceyhan B, Alhorn P, et al.Magneto immuno-PCR:a novel immunoassay based on biogenic magnetosome nanoparticles[J]. Biochemical and Biophysical Research Communications, 2007, 357(2):391-396.