强磁场生命科学与健康医疗的机遇和挑战
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摘要
基于第620次香山科学会议的研讨主题和内容,从强磁设备平台、强磁场生命科学研究、铁代谢与铁磁纳米药物、强磁场健康调控等方面论述了强磁场生命科学与健康医学领域的新问题、新机遇以及面临的挑战.
High magnetic fields are unique artificial physical environments. Since 1913, more than 10 Nobel prizes were given to novel findings related to high magnetic fields in the areas of high-temperature superconductivity, new materials, and life sciences. In recent years, progress in superconducting technologies has dramatically enhanced the application of high magnetic fields in scientific research, industry, and healthcare. Many countries have established national-level high magnetic research centers to strengthen scientific research in magnetic fields. The National High Magnetic Field Laboratory at Florida State University in the United States, the Grenoble High Magnetic Field Laboratory in France, the High Field Magnet Laboratory in Nijmegen in Netherlands, the Tsukuba Magnet Laboratory in Japan, and the High Magnetic Field Laboratory of the Chinese Academy of Sciences in China are the most recognized magnetic field research centers worldwide. Of these institutions, the High Magnetic Field Laboratory in China has a unique research team focused on magnetic field life science research. Current progress at Chinese institutions in high-level talent teams, scientific research, and industry applications is significant and has achieved considerable international influence. In April 2018, the 620 th session of the Xiangshan Science Conference, "High Magnetic Field and Life Health: New Conditions, New Questions, New Opportunities", was held in Beijing. This conference attracted more than 40 participants from approximately 30 domestic and international institutions. The following central issues were discussed at the conference:(1) the theory and techniques of high magnetic equipment based on novel superconductive materials;(2) fundamental life science research under high magnetic fields;(3) magnetic nanoparticle medication and iron metabolism; and(4) applications of dynamic magnetic fields in human health care and medicine. The present paper offers a comprehensive summary of the opinions, views, and visions collected during this conference. In addition, this paper reviews recent progress in the interdisciplinary field of high magnetic fields and life science and healthcare. For each central issue discussed in the 620 th session of the Xiangshan Science Conference, this review gives a brief summary of the current advancements and challenging problems in research. The key scientific questions and application techniques in this field and the strategic thinking and landscape planning of the scientific research are promoted. Several unknown questions and future directions of innovative and featured research are identified in this paper. First, the scientific questions in the field need to be refined. Moreover, it is necessary to consider how to achieve scientific breakthroughs and high-level scientific research results with the scientific and technical advantages that currently exist in China. Second, the translation-oriented interdisciplinary scientific research in this field needs to be one of the primary research directions to produce innovative principles, methods, and technologies for healthcare and medical treatments. Third, the cooperation of the research groups in China needs to be enhanced to advance the fundamental and application research of life sciences, health, and medical care with respect to high magnetic fields.
High magnetic fields are unique artificial physical environments. Since 1913, more than 10 Nobel prizes were given to novel findings related to high magnetic fields in the areas of high-temperature superconductivity, new materials, and life sciences. In recent years, progress in superconducting technologies has dramatically enhanced the application of high magnetic fields in scientific research, industry, and healthcare. Many countries have established national-level high magnetic research centers to strengthen scientific research in magnetic fields. The National High Magnetic Field Laboratory at Florida State University in the United States, the Grenoble High Magnetic Field Laboratory in France, the High Field Magnet Laboratory in Nijmegen in Netherlands, the Tsukuba Magnet Laboratory in Japan, and the High Magnetic Field Laboratory of the Chinese Academy of Sciences in China are the most recognized magnetic field research centers worldwide. Of these institutions, the High Magnetic Field Laboratory in China has a unique research team focused on magnetic field life science research. Current progress at Chinese institutions in high-level talent teams, scientific research, and industry applications is significant and has achieved considerable international influence. In April 2018, the 620 th session of the Xiangshan Science Conference, "High Magnetic Field and Life Health: New Conditions, New Questions, New Opportunities", was held in Beijing. This conference attracted more than 40 participants from approximately 30 domestic and international institutions. The following central issues were discussed at the conference:(1) the theory and techniques of high magnetic equipment based on novel superconductive materials;(2) fundamental life science research under high magnetic fields;(3) magnetic nanoparticle medication and iron metabolism; and(4) applications of dynamic magnetic fields in human health care and medicine. The present paper offers a comprehensive summary of the opinions, views, and visions collected during this conference. In addition, this paper reviews recent progress in the interdisciplinary field of high magnetic fields and life science and healthcare. For each central issue discussed in the 620 th session of the Xiangshan Science Conference, this review gives a brief summary of the current advancements and challenging problems in research. The key scientific questions and application techniques in this field and the strategic thinking and landscape planning of the scientific research are promoted. Several unknown questions and future directions of innovative and featured research are identified in this paper. First, the scientific questions in the field need to be refined. Moreover, it is necessary to consider how to achieve scientific breakthroughs and high-level scientific research results with the scientific and technical advantages that currently exist in China. Second, the translation-oriented interdisciplinary scientific research in this field needs to be one of the primary research directions to produce innovative principles, methods, and technologies for healthcare and medical treatments. Third, the cooperation of the research groups in China needs to be enhanced to advance the fundamental and application research of life sciences, health, and medical care with respect to high magnetic fields.
引文
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2 Guo X,Li W,Luo L,et al.External Magnetic field-enhanced chemo-photothermal combination tumor therapy via iron oxide nanoparticles.ACS Appl Mater Interfaces,2017,9:16581-16593
3 Liao J,Wei X,Ran B,et al.Polymer hybrid magnetic nanocapsules encapsulating IR820 and PTX for external magnetic field-guided tumor targeting and multifunctional theranostics.Nanoscale,2017,9:2479-2491
4 Crielaard B J,Lammers T,Rivella S.Targeting iron metabolism in drug discovery and delivery.Nat Rev Drug Discov,2017,16:400-423
5 Qian A,Yin D,Yang P,et al.Development of a ground-based simulated experimental platform for gravitational biology.IEEE Trans Appl Supercon,2009,19:42-46
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9 Nowogrodzki A.The world’s strongest MRI machines are pushing human imaging to new limits.Nature,2018,563:24-26
10 Zhang L,Wang J,Wang H,et al.Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation.Oncotarget,2016,7:41527-41539
11 Zhang L,Hou Y,Li Z,et al.27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells.Elife,2017,6:e2291113
12 Tian X,Wang Z,Zhang L,et al.The effects of 3.7-24.5 T high magnetic fields on tumor bearing mice.Chin Phys B,2018,27:118703
13 Luo Y,Ji X,Liu J,et al.Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and Taxol.Bioelectrochemistry,2016,109:31-40
14 Zhang L,Yang X,Liu J,et al.1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of mTOR inhibitors in CNE-2Z cells.Sci Bull,2015,60:2120-2128
15 Wang J,Zhang L,Hu C,et al.Sub-molecular features of single proteins in solution resolved with scanning tunneling microscopy.Nano Res,2016,9:2551-2560
16 Sabo J,Mirossay L,Horovcak L,et al.Effects of static magnetic field on human leukemic cell line HL-60.Bioelectrochemistry,2002,56:227-231
17 Ghodbane S,Lahbib A,Sakly M,et al.Bioeffects of static magnetic fields:Oxidative stress,genotoxic effects,and cancer studies.BioMed Res Int,2013,7:307-315
18 Spyridopoulou K,Makridis A,Maniotis N,et al.Effect of low frequency magnetic fields on the growth of MNP-treated HT29 colon cancer cells.Nanotechnology,2018,29:175101
19 Yin D C.Protein crystallization in a magnetic field.Prog Cryst Growth Ch,2015,611:1-26
20 Lu H M,Lu X L,Zhai J H,et al.Effects of large gradient high magnetic field(LG-HMF)on the long-term culture of aquatic organisms:Planarians example.Bioelectromagnetics,2018,39:428-440
21 Lu H M,Yin D C,Li H S,et al.A containerless levitation setup for liquid processing in a superconducting magnet.Rev Sci Instrum,2008,79:729
22 Dixon S J,Lemberg K M,Lamprecht M R,et al.Ferroptosis:An iron-dependent form of nonapoptotic cell death.Cell,2012,1495:1060-1072
23 Viswanathan V S,Ryan M J,Dhruv H D,et al.Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway.Nature,2017,547:453-457
24 Yang J,Zhang J,Ding C,et al.Regulation of osteoblast differentiation and iron content in MC3T3-E1 cells by static magnetic field with different intensities.Biol Trace Elem Res,2018,184:214-225
25 Du S,Li J,Du C,et al.Overendocytosis of superparamagnetic iron oxide particles increases apoptosis and triggers autophagic cell death in human osteosarcoma cell under a spinning magnetic field.Oncotarget,2017,8:9410-9424
26 Zhang H,Li J,Hu Y,et al.Folic acid-targeted iron oxide nanoparticles as contrast agents for magnetic resonance imaging of human ovarian cancer.J Ovarian Res,2016,9:19
27 Foy S P,Manthe R L,Foy S T,et al.Optical imaging and magnetic field targeting of magnetic nanoparticles in tumors.ACS Nano,2011,4:5217-5224
28 Lu M,Cohen M H,Rieves D,et al.FDA report:Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease.Am J Hematol,2010,85:315-319
29 Chen B,Gu N.Current status and development of pharmaceutical iron based nanomaterials(in Chinese).Mater Chin,2017,3:46-50[陈博,顾宁.药用铁基纳米材料及其发展前景.中国材料进展,2017,3:46-50]
30 Lv H H,Dong D D,Yang J C,et al.Research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy(in Chinese).Int J Biomed Eng,2017,40:65-70[吕欢欢,董丹丹,杨建成,等.静磁场靶向药物递送系统在肿瘤诊疗中的研究进展.国际生物医学工程杂志,2017,40:65-70]
31 Han J,Go G,Zhen J,et al.Feasibility study of dual-targeting paclitaxel-loaded magnetic liposomes using electromagnetic actuation and macrophages.Sensor Actuat B Chem,2017,240:1226-1236
32 Boris P,Gary F.Magnetic targeting for site-specific drug delivery:Applications and clinical potential.Expert Opin Drug Deliv,2009,6:53-70
33 Muthana M,Kennerley A J,Hughes R,et al.Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting.Nat Commun,2015,6:8009
34 Oka C,Ushimaru K,Horiishi N,et al.Core-shell composite particles composed of biodegradable polymer particles and magnetic iron oxide nanoparticles for targeted drug delivery.J Magn Magn Mater,2015,381:278-284
35 Riccardo D C,Bigall N C,Andrea R,et al.Multifunctional nanobeads based on quantum dots and magnetic nanoparticles:synthesis and cancer cell targeting and sorting.ACS Nano,2011,5:1109-1121
36 Elumalai R,Patil S,Maliyakkal N,et al.Protamine-carboxymethyl cellulose magnetic nanocapsules for enhanced delivery of anticancer drugs against drug resistant cancers.Nanomed-Nanotechnol,2015,11:969-981
37 Morris C E,Skalak T C.Acute exposure to a moderate strength static magnetic field reduces edema formation in rats.Am J Physiol Heart Circ Physiol,2008,294:H50
38 Markov M S.Magnetic field therapy:A review.Electromag Biol Med,2007,26:1-23
39 Mar C,Bohórquez A C,Madeline T L,et al.EGFR-targeted magnetic nanoparticle heaters kill cancer cells without a perceptible temperature rise.ACS Nano,2011,5:7124-7129
40 Guo D L,Yang J,Luo Y C,et al.A feasibility study of low frequency rotating magnetic field in the treatment of high altitude polycythemia(in Chinese).Chin J Biomed Eng,2016,35:124-127[郭大龙,杨军,罗永昌,等.采用低频旋转磁场治疗高原红细胞增多症的可行性研究.中国生物医学工程学报,2016,35:124-127]
2 Guo X,Li W,Luo L,et al.External Magnetic field-enhanced chemo-photothermal combination tumor therapy via iron oxide nanoparticles.ACS Appl Mater Interfaces,2017,9:16581-16593
3 Liao J,Wei X,Ran B,et al.Polymer hybrid magnetic nanocapsules encapsulating IR820 and PTX for external magnetic field-guided tumor targeting and multifunctional theranostics.Nanoscale,2017,9:2479-2491
4 Crielaard B J,Lammers T,Rivella S.Targeting iron metabolism in drug discovery and delivery.Nat Rev Drug Discov,2017,16:400-423
5 Qian A,Yin D,Yang P,et al.Development of a ground-based simulated experimental platform for gravitational biology.IEEE Trans Appl Supercon,2009,19:42-46
6 Zhang X,Yarema K,Xu A.Zhang L,Liu J J,Trans.Biological Effects of Static Magnetic Fields(in Chinese).Beijing:Science Press,2018[张欣,Kevin Yarema,许安.张磊,刘娟娟,译.稳态磁场的生物学效应.北京:科学出版社,2018]
7 Zhang X,Wang J.Interdisciplinary Research of Magnetic Fields and Life Sciences(in Chinese).Beijing:Science Press,2018[张欣,王俊峰.磁场与生命科学的跨学科研究.北京:科学出版社,2018]
8 Wang Q,Dai Y,Zhao B,et al.Development of high magnetic field superconducting magnet technology and applications in China.Cryogenics,2007,47:364-379
9 Nowogrodzki A.The world’s strongest MRI machines are pushing human imaging to new limits.Nature,2018,563:24-26
10 Zhang L,Wang J,Wang H,et al.Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation.Oncotarget,2016,7:41527-41539
11 Zhang L,Hou Y,Li Z,et al.27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells.Elife,2017,6:e2291113
12 Tian X,Wang Z,Zhang L,et al.The effects of 3.7-24.5 T high magnetic fields on tumor bearing mice.Chin Phys B,2018,27:118703
13 Luo Y,Ji X,Liu J,et al.Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and Taxol.Bioelectrochemistry,2016,109:31-40
14 Zhang L,Yang X,Liu J,et al.1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of mTOR inhibitors in CNE-2Z cells.Sci Bull,2015,60:2120-2128
15 Wang J,Zhang L,Hu C,et al.Sub-molecular features of single proteins in solution resolved with scanning tunneling microscopy.Nano Res,2016,9:2551-2560
16 Sabo J,Mirossay L,Horovcak L,et al.Effects of static magnetic field on human leukemic cell line HL-60.Bioelectrochemistry,2002,56:227-231
17 Ghodbane S,Lahbib A,Sakly M,et al.Bioeffects of static magnetic fields:Oxidative stress,genotoxic effects,and cancer studies.BioMed Res Int,2013,7:307-315
18 Spyridopoulou K,Makridis A,Maniotis N,et al.Effect of low frequency magnetic fields on the growth of MNP-treated HT29 colon cancer cells.Nanotechnology,2018,29:175101
19 Yin D C.Protein crystallization in a magnetic field.Prog Cryst Growth Ch,2015,611:1-26
20 Lu H M,Lu X L,Zhai J H,et al.Effects of large gradient high magnetic field(LG-HMF)on the long-term culture of aquatic organisms:Planarians example.Bioelectromagnetics,2018,39:428-440
21 Lu H M,Yin D C,Li H S,et al.A containerless levitation setup for liquid processing in a superconducting magnet.Rev Sci Instrum,2008,79:729
22 Dixon S J,Lemberg K M,Lamprecht M R,et al.Ferroptosis:An iron-dependent form of nonapoptotic cell death.Cell,2012,1495:1060-1072
23 Viswanathan V S,Ryan M J,Dhruv H D,et al.Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway.Nature,2017,547:453-457
24 Yang J,Zhang J,Ding C,et al.Regulation of osteoblast differentiation and iron content in MC3T3-E1 cells by static magnetic field with different intensities.Biol Trace Elem Res,2018,184:214-225
25 Du S,Li J,Du C,et al.Overendocytosis of superparamagnetic iron oxide particles increases apoptosis and triggers autophagic cell death in human osteosarcoma cell under a spinning magnetic field.Oncotarget,2017,8:9410-9424
26 Zhang H,Li J,Hu Y,et al.Folic acid-targeted iron oxide nanoparticles as contrast agents for magnetic resonance imaging of human ovarian cancer.J Ovarian Res,2016,9:19
27 Foy S P,Manthe R L,Foy S T,et al.Optical imaging and magnetic field targeting of magnetic nanoparticles in tumors.ACS Nano,2011,4:5217-5224
28 Lu M,Cohen M H,Rieves D,et al.FDA report:Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease.Am J Hematol,2010,85:315-319
29 Chen B,Gu N.Current status and development of pharmaceutical iron based nanomaterials(in Chinese).Mater Chin,2017,3:46-50[陈博,顾宁.药用铁基纳米材料及其发展前景.中国材料进展,2017,3:46-50]
30 Lv H H,Dong D D,Yang J C,et al.Research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy(in Chinese).Int J Biomed Eng,2017,40:65-70[吕欢欢,董丹丹,杨建成,等.静磁场靶向药物递送系统在肿瘤诊疗中的研究进展.国际生物医学工程杂志,2017,40:65-70]
31 Han J,Go G,Zhen J,et al.Feasibility study of dual-targeting paclitaxel-loaded magnetic liposomes using electromagnetic actuation and macrophages.Sensor Actuat B Chem,2017,240:1226-1236
32 Boris P,Gary F.Magnetic targeting for site-specific drug delivery:Applications and clinical potential.Expert Opin Drug Deliv,2009,6:53-70
33 Muthana M,Kennerley A J,Hughes R,et al.Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting.Nat Commun,2015,6:8009
34 Oka C,Ushimaru K,Horiishi N,et al.Core-shell composite particles composed of biodegradable polymer particles and magnetic iron oxide nanoparticles for targeted drug delivery.J Magn Magn Mater,2015,381:278-284
35 Riccardo D C,Bigall N C,Andrea R,et al.Multifunctional nanobeads based on quantum dots and magnetic nanoparticles:synthesis and cancer cell targeting and sorting.ACS Nano,2011,5:1109-1121
36 Elumalai R,Patil S,Maliyakkal N,et al.Protamine-carboxymethyl cellulose magnetic nanocapsules for enhanced delivery of anticancer drugs against drug resistant cancers.Nanomed-Nanotechnol,2015,11:969-981
37 Morris C E,Skalak T C.Acute exposure to a moderate strength static magnetic field reduces edema formation in rats.Am J Physiol Heart Circ Physiol,2008,294:H50
38 Markov M S.Magnetic field therapy:A review.Electromag Biol Med,2007,26:1-23
39 Mar C,Bohórquez A C,Madeline T L,et al.EGFR-targeted magnetic nanoparticle heaters kill cancer cells without a perceptible temperature rise.ACS Nano,2011,5:7124-7129
40 Guo D L,Yang J,Luo Y C,et al.A feasibility study of low frequency rotating magnetic field in the treatment of high altitude polycythemia(in Chinese).Chin J Biomed Eng,2016,35:124-127[郭大龙,杨军,罗永昌,等.采用低频旋转磁场治疗高原红细胞增多症的可行性研究.中国生物医学工程学报,2016,35:124-127]