磁性纳米粒子介导的细胞生物学效应
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摘要
磁性纳米粒子(magnetic nanoparticles, MNPs)由于其独特磁响应性,可将外加磁场的能量转化为机械能和热能。磁性纳米粒子介导的物理信号依赖于MNPs本身的磁学性能及磁场的参数,可定量输出作用于不同类型的细胞,调控细胞命运。MNPs本身Fe~(2+)引发芬顿反应可上调化学信号(reactive oxygen species, ROS),用于肿瘤治疗;在超低频磁场(<1 Hz)下产生的机械力可诱导干细胞分化和巨噬细胞极化等过程,用于再生医学领域;在低频磁场(1～100 Hz)下产生的机械力可通过直接物理破坏或间接触发生物信号通路,引起肿瘤细胞死亡;在高频磁场(100 kHz～1 MHz)下产生的热可破坏肿瘤细胞,在神经元信号转导领域也取得一定的突破。研究MNPs介导的化学、物理、生物信号引起的细胞生物学效应对MNPs的设计和磁场的选择具有重要的指导意义。本文就MNPs在不同类型磁场下介导的细胞生物学效应做一概述。
Magnetic nanoparticles(MNPs) can convert magnetic field energy into mechanical or thermal energy due to their unique magnetic responses. MNPs-mediated physical signals depend on its magnetic properties and magnetic field parameters, which can be quantitatively exported to different types of cells and manipulate the fate of cells. Intrinsic Fe~(2+) of MNPs triggered Fenton reaction, can upregulate the chemical signal ROS(reactive oxygen species), which is used for tumor treatment. Under ultra-low frequency magnetic field(<1 Hz), the mechanical force generated can induce stem cell differentiation, macrophage polarization and other processes, which are used in the field of regenerative medicine. Under low-frequency magnetic field(1-100 Hz), the mechanical force can directly destroy cells or indirectly trigger the biological signaling pathway, resulting in tumor cells death. Under high-frequency magnetic fields(100 kHz-1 MHz), heat can destruct tumor cells, and some breakthroughs have been made in the field of neuron signal transduction. It is important to investigate the cellular biological effects triggered by chemical, physical and biological signals, owing to prior guidance for design of MNPs and selection of magnetic field. This paper gives an overview of the cell biological effects mediated by MNPs under different types of magnetic fields.
Magnetic nanoparticles(MNPs) can convert magnetic field energy into mechanical or thermal energy due to their unique magnetic responses. MNPs-mediated physical signals depend on its magnetic properties and magnetic field parameters, which can be quantitatively exported to different types of cells and manipulate the fate of cells. Intrinsic Fe~(2+) of MNPs triggered Fenton reaction, can upregulate the chemical signal ROS(reactive oxygen species), which is used for tumor treatment. Under ultra-low frequency magnetic field(<1 Hz), the mechanical force generated can induce stem cell differentiation, macrophage polarization and other processes, which are used in the field of regenerative medicine. Under low-frequency magnetic field(1-100 Hz), the mechanical force can directly destroy cells or indirectly trigger the biological signaling pathway, resulting in tumor cells death. Under high-frequency magnetic fields(100 kHz-1 MHz), heat can destruct tumor cells, and some breakthroughs have been made in the field of neuron signal transduction. It is important to investigate the cellular biological effects triggered by chemical, physical and biological signals, owing to prior guidance for design of MNPs and selection of magnetic field. This paper gives an overview of the cell biological effects mediated by MNPs under different types of magnetic fields.
引文
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[19]Wang Q,Chen B,Cao M,et al.Response of MAPKpathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of h BMSCs.Biomaterials,2016,86:11-20
[20]Chen H,Sun J,Wang Z,et al.Magnetic cell-scaffold interface constructed by superparamagnetic IONPs enhanced osteogenesis of adipose-derived stem cells.ACSAppl Mater Interfaces,2018,10(51):44279-44289
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[22]Monzel C,Vicario C,Piehler J,et al.Magnetic control of cellular processes using biofunctional nanoparticles.Chem Sci,2017,8(11):7330-7338
[23]Shin TH,Cheon J.Synergism of nanomaterials with physical stimuli for biology and medicine.Acc Chem Res,2017,50(3):567-572
[24]Kim DH,Rozhkova EA,Ulasov IV,et al.Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction.Nat Mater,2010,9(2):165-171
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[27]Hu SH,Gao X.Nanocomposites with spatially separated functionalities for combined imaging and magetolytic therapy.J Am Chem Soc,2010,132:7234-7237
[28]Zhang L,Zhao Y,Wang X.Nanoparticle-mediated mechanical destruction of cell membranes:A coarse-grained molecular dynamics study.ACS Appl Mater Interfaces,2017,9(32):26665-26673
[29]Zhang E,Kircher MF,Koch M,et al.Dynamic magnetic fields remote-control apoptosis via nanoparticle rotation.ACS Nano,2014,8(4):3192-3201
[30]Shen Y,Wu C,Uyeda TQP,et al.Elongated nanoparticle aggregates in cancer cells for mechanical destruction with low frequency rotating magnetic field.Theranostics,2017,7(6):1735-1748
[31]Master AM,Williams PN,Pothayee N,et al.Remote actuation of magnetic nanoparticles for cancer cell selective treatment through cytoskeletal disruption.Sci Rep,2016,6:33560
[32]Meyer CJ,Alenghat FJ,Rim P,et al.Mechniacal control of cyclic AMP signalling and gene transcription through integrins.Nat Cell Biol,2000,2:666-668
[33]Seo D,Southard KM,Kim JW,et al.A mechanogenetic toolkit for interrogating cell signaling in space and time.Cell,2016,165(6):1507-1518
[34]Kim JW,Seo D,Lee JU,et al.Single-cell mechanogenetics using monovalent magnetoplasmonic nanoparticles.Nat Protoc,2017,12(9):1871-1889
[35]Kwak M,Gu W,Jeong H,et al.Small,clickable,and monovalent magnetofluorescent nanoparticles enable mechanogenetic regulation of receptors in a crowded live-cell microenvironment.Nano Lett,2019,19(6):3761-3769
[36]Cho MH,Lee EJ,Son M,et al.A magnetic switch for the control of cell death signalling in in vitro and in vivo systems.Nat Mater,2012,11(12):1038-1043
[37]Cho MH,Kim S,Lee JH,et al.Magnetic tandem apoptosis for overcoming multidrug-resistant cancer.Nano Lett,2016,16(12):7455-7460
[38]Lee JH,Kim ES,Cho MH,et al.Artificial control of cell signaling and growth by magnetic nanoparticles.Angew Chem Int Ed Engl,2010,49(33):5698-5702
[39]Mannix RJ,Kumar S,Cassiola F,et al.Nanomagnetic actuation of receptor-mediated signal transduction.Nat Nanotechnol,2008,3(1):36-40
[40]Kang H,Wong DSH,Yan X,et al.Remote control of multimodal nanoscale ligand oscillations regulates stem cell adhesion and differentiation.ACS Nano,2017,11(10):9636-9649
[41]Wong DS,Li J,Yan X,et al.Magnetically tuning tether mobility of integrin ligand regulates adhesion,spreading,and differentiation of stem cells.Nano Lett,2017,17(3):1685-1695
[42]Kang H,Jung HJ,Wong DSH,et al.Remote control of heterodimeric magnetic nanoswitch regulates the adhesion and differentiation of stem cells.J Am Chem Soc,2018,140(18):5909-5913
[43]Hu B,El Haj AJ,Dobson J.Receptor-targeted,magneto-mechanical stimulation of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.Int J Mol Sci,2013,14(9):19276-19293
[44]Kanczler JM,Sura HS,Magnay J,et al.Controlled differentiation of human bone marrow stromal cells using magnetic nanoparticle technology.Tissue Eng Part A,2010,16(10):3241-3250
[45]Kang H,Kim S,Wong DSH,et al.Remote manipulation of ligand nano-oscillations regulates adhesion and polarization of macrophages in vivo.Nano Lett,2017,17(10):6415-6427
[46]Kang H,Jung HJ,Kim SK,et al.Magnetic manipulation of reversible nanocaging controls in vivo adhesion and polarization of macrophages.ACS Nano,2018,12(6):5978-5994
[47]Dobson J.Remote control of cellular behaviour with magnetic nanoparticles.Nat Nanotechnol,2008,3:139-143
[48]Lee JH,Kim J,Levy M,et al.Magnetic nanoparticles for ultrafast mechanical control of inner ear hair cells.ACSNano,2014,8(7):6590-6598
[49]Kirkham GR,Elliot KJ,Keramane A,et al.Hyperpolarization of human mesenchymal stem cells in response to magnetic force.IEEE Trans Nanobiosci,2010,9(1):71-74
[50]Hughes S,Mc Bain S,Dobson J,et al.Selective activation of mechnosensitive ion channels using magnetic particles.J R Soc Interface,2008,5:855-863
[51]Gilchrist RK,D M,Medal R,et al.Selective inductive heating of lymph nodes.Ann Surg,1957,146(4):596-606
[52]Clerc P,Jeanjean P,Hallali N,et al.Targeted magnetic intra-lysosomal hyperthermia produces lysosomal reactive oxygen species and causes caspase-1 dependent cell death.J Control Release,2018,270:120-134
[53]Sanchez C,Diab DEH,Cannord V,et al.Targeting a G-protein-coupled recceptor overexpressed in endocrine tumors by magnetic nanoparticles to induce cell death.ACS Nano,2014,8(2):1350-1363
[54]Alvarez-Berrios MP,Castillo A,Merida F,et al.Enhanced proteotoxic stress:one of the contributors for hyperthermic potentiation of the proteasome inhibitor bortezomib using magnetic nanoparticles.Biomater Sci,2015,3(2):391-400
[55]Prasad NK,Rathinasamy K,Panda D,et al.Mechanism of cell death induced by magnetic hyperthermia with nanoparticles ofγ-Mnx Fe2-x O3 synthesized by a single step process.J Mater Chem,2007,17(48):5042-5051
[56]Lin FC,Hsu CH,Lin YY.Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins:insights from mathematical modeling.Int JNanomed,2018,13:3529-3539
[57]Huang H,Delikanli S,Zeng H,et al.Remote control of ion channels and neurons through magnetic-field heating of nanoparticles.Nat Nanotechnol,2010,5(8):602-606
[58]Chen R,Romero G,Christiansen MG,et al.Wireless magnetothermal deep brain stimulation.Science,2015,347(6229):1477-1480
[59]Stanley SA,Gagner JE,Damanpour S,et al.Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice.Science,2012,336(6081):604-608
[60]Stanley SA,Sauer J,Kane RS,et al.Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles.Nat Med,2015,21(1):92-98
[61]Stanley SA,Kelly L,Latcha KN,et al.Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism.Nature,2016,531(7596):647-650
[62]Cao Z,Wang D,Li Y,et al.Effect of nanoheat stimulation mediated by magnetic nanocomposite hydrogel on the osteogenic differentiation of mesenchymal stem cells.Sci China Life Sci,2018,61(4):448-456
[63]Moise S,Byrne JM,El Haj AJ,et al.The potential of magnetic hyperthermia for triggering the differentiation of cancer cells.Nanoscale,2018,10(44):20519-20525
[2]Tang Q,Zhang Y,He Y,et al.Progress in biomedical applications of magnetic nanomaterials.Prog Biochem Biophys,2019,46(4):353-368
[3]Jun Y,Huh YM,Choi J,et al.Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging.J Am Chem Soc,2005,127:5732-5733
[4]Jang JT,Nah H,Lee JH,et al.Criticalenhancements of MRI contrast and hyperthermic effects by dopant-controlled magnetic nanoparticles.Angew Chem Int Edit,2009,48(7):1234-1238
[5]Noh SH,Na W,Jang JT,et al.Nanoscale magnetism control via surface and exchange anisotropy for optimized ferrimagnetic hysteresis.Nano Lett,2012,12(7):3716-3721
[6]Liu X,Peng M,Li G,et al.Ultrasonication-triggered ubiquitous assembly of magnetic janus amphiphilic nanoparticles in cancer theranostic applications.Nano Lett,2019,19:4118-4125
[7]Park JI,Jun YW,Choi JS,et al.Highly crystalline anisotropic superstructures via magnetic field induced nanoparticle assembly.Chem Commun(Camb),2007,(47):5001-5003
[8]Fantechi E,Campo G,Carta D,et al.Exploring the effect of Co doping in fine maghemite nanoparticles.J Phys Chem C,2012,116(14):8261-8270
[9]Lee JH,Jang JT,Choi JS,et al.Exchange-coupled magnetic nanoparticles for efficient heat induction.Nat Nanotechnol,2011,6(7):418-422
[10]Pankhurst QA,Connolly J,Jones SK,et al.Applications of magnetic nanoparticles in biomedicine.J Phys D Appl Phys,2003,36:R167-R181
[11]Wu C,Shen Y,Chen M,et al.Recent advances in magnetic-nanomaterial-based mechanotransduction for cell fate regulation.Adv Mater,2018,30(17):e1705673
[12]Noh SH,Moon SH,Shin TH,et al.Recent advances of magneto-thermal capabilities of nanoparticles:From design principles to biomedical applications.Nano Today,2017,13:61-76
[13]Tian X,Zhang X.Biological effects on cells in strong static magnetic field.Acta Phys Sin,2018,67(14):148701
[14]冯爽,纪新苗,张欣.中等强度极低频旋转磁场的生物学效应.中国细胞生物学学报,2018,40(3):309-317
[15]王慧珍,廖钟财,王冬梅,等.静磁场与活性氧.生命的化学,2019,39(2):217-228
[16]Shen Z,Song J,Yung BC,et al.Emerging strategies of cancer therapy based on ferroptosis.Adv Mater,2018,30(12):e1704007
[17]Stockwell BR,Friedmann Angeli JP,Bayir H,et al.Ferroptosis:A regulated cell death nexus linking metabolism,redox biology,and disease.Cell,2017,171(2):273-285
[18]Fenton HJH.Oxidation of tartaric acid in prescence of iron.J Am Chem Soc,1894,65:899-910
[19]Wang Q,Chen B,Cao M,et al.Response of MAPKpathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of h BMSCs.Biomaterials,2016,86:11-20
[20]Chen H,Sun J,Wang Z,et al.Magnetic cell-scaffold interface constructed by superparamagnetic IONPs enhanced osteogenesis of adipose-derived stem cells.ACSAppl Mater Interfaces,2018,10(51):44279-44289
[21]Zanganeh S,Hutter G,Spitler R,et al.Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues.Nat Nanotechnol,2016,11(11):986-994
[22]Monzel C,Vicario C,Piehler J,et al.Magnetic control of cellular processes using biofunctional nanoparticles.Chem Sci,2017,8(11):7330-7338
[23]Shin TH,Cheon J.Synergism of nanomaterials with physical stimuli for biology and medicine.Acc Chem Res,2017,50(3):567-572
[24]Kim DH,Rozhkova EA,Ulasov IV,et al.Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction.Nat Mater,2010,9(2):165-171
[25]Dobson J.Cancer therapy:A twist on tumour targeting.Nat Mater,2010,9(2):95-96
[26]Tomasini MD,Rinaldi C,Tomassone MS.Molecular dynamics simulations of rupture in lipid bilayers.Exp Biol Med(Maywood),2010,235(2):181-188
[27]Hu SH,Gao X.Nanocomposites with spatially separated functionalities for combined imaging and magetolytic therapy.J Am Chem Soc,2010,132:7234-7237
[28]Zhang L,Zhao Y,Wang X.Nanoparticle-mediated mechanical destruction of cell membranes:A coarse-grained molecular dynamics study.ACS Appl Mater Interfaces,2017,9(32):26665-26673
[29]Zhang E,Kircher MF,Koch M,et al.Dynamic magnetic fields remote-control apoptosis via nanoparticle rotation.ACS Nano,2014,8(4):3192-3201
[30]Shen Y,Wu C,Uyeda TQP,et al.Elongated nanoparticle aggregates in cancer cells for mechanical destruction with low frequency rotating magnetic field.Theranostics,2017,7(6):1735-1748
[31]Master AM,Williams PN,Pothayee N,et al.Remote actuation of magnetic nanoparticles for cancer cell selective treatment through cytoskeletal disruption.Sci Rep,2016,6:33560
[32]Meyer CJ,Alenghat FJ,Rim P,et al.Mechniacal control of cyclic AMP signalling and gene transcription through integrins.Nat Cell Biol,2000,2:666-668
[33]Seo D,Southard KM,Kim JW,et al.A mechanogenetic toolkit for interrogating cell signaling in space and time.Cell,2016,165(6):1507-1518
[34]Kim JW,Seo D,Lee JU,et al.Single-cell mechanogenetics using monovalent magnetoplasmonic nanoparticles.Nat Protoc,2017,12(9):1871-1889
[35]Kwak M,Gu W,Jeong H,et al.Small,clickable,and monovalent magnetofluorescent nanoparticles enable mechanogenetic regulation of receptors in a crowded live-cell microenvironment.Nano Lett,2019,19(6):3761-3769
[36]Cho MH,Lee EJ,Son M,et al.A magnetic switch for the control of cell death signalling in in vitro and in vivo systems.Nat Mater,2012,11(12):1038-1043
[37]Cho MH,Kim S,Lee JH,et al.Magnetic tandem apoptosis for overcoming multidrug-resistant cancer.Nano Lett,2016,16(12):7455-7460
[38]Lee JH,Kim ES,Cho MH,et al.Artificial control of cell signaling and growth by magnetic nanoparticles.Angew Chem Int Ed Engl,2010,49(33):5698-5702
[39]Mannix RJ,Kumar S,Cassiola F,et al.Nanomagnetic actuation of receptor-mediated signal transduction.Nat Nanotechnol,2008,3(1):36-40
[40]Kang H,Wong DSH,Yan X,et al.Remote control of multimodal nanoscale ligand oscillations regulates stem cell adhesion and differentiation.ACS Nano,2017,11(10):9636-9649
[41]Wong DS,Li J,Yan X,et al.Magnetically tuning tether mobility of integrin ligand regulates adhesion,spreading,and differentiation of stem cells.Nano Lett,2017,17(3):1685-1695
[42]Kang H,Jung HJ,Wong DSH,et al.Remote control of heterodimeric magnetic nanoswitch regulates the adhesion and differentiation of stem cells.J Am Chem Soc,2018,140(18):5909-5913
[43]Hu B,El Haj AJ,Dobson J.Receptor-targeted,magneto-mechanical stimulation of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.Int J Mol Sci,2013,14(9):19276-19293
[44]Kanczler JM,Sura HS,Magnay J,et al.Controlled differentiation of human bone marrow stromal cells using magnetic nanoparticle technology.Tissue Eng Part A,2010,16(10):3241-3250
[45]Kang H,Kim S,Wong DSH,et al.Remote manipulation of ligand nano-oscillations regulates adhesion and polarization of macrophages in vivo.Nano Lett,2017,17(10):6415-6427
[46]Kang H,Jung HJ,Kim SK,et al.Magnetic manipulation of reversible nanocaging controls in vivo adhesion and polarization of macrophages.ACS Nano,2018,12(6):5978-5994
[47]Dobson J.Remote control of cellular behaviour with magnetic nanoparticles.Nat Nanotechnol,2008,3:139-143
[48]Lee JH,Kim J,Levy M,et al.Magnetic nanoparticles for ultrafast mechanical control of inner ear hair cells.ACSNano,2014,8(7):6590-6598
[49]Kirkham GR,Elliot KJ,Keramane A,et al.Hyperpolarization of human mesenchymal stem cells in response to magnetic force.IEEE Trans Nanobiosci,2010,9(1):71-74
[50]Hughes S,Mc Bain S,Dobson J,et al.Selective activation of mechnosensitive ion channels using magnetic particles.J R Soc Interface,2008,5:855-863
[51]Gilchrist RK,D M,Medal R,et al.Selective inductive heating of lymph nodes.Ann Surg,1957,146(4):596-606
[52]Clerc P,Jeanjean P,Hallali N,et al.Targeted magnetic intra-lysosomal hyperthermia produces lysosomal reactive oxygen species and causes caspase-1 dependent cell death.J Control Release,2018,270:120-134
[53]Sanchez C,Diab DEH,Cannord V,et al.Targeting a G-protein-coupled recceptor overexpressed in endocrine tumors by magnetic nanoparticles to induce cell death.ACS Nano,2014,8(2):1350-1363
[54]Alvarez-Berrios MP,Castillo A,Merida F,et al.Enhanced proteotoxic stress:one of the contributors for hyperthermic potentiation of the proteasome inhibitor bortezomib using magnetic nanoparticles.Biomater Sci,2015,3(2):391-400
[55]Prasad NK,Rathinasamy K,Panda D,et al.Mechanism of cell death induced by magnetic hyperthermia with nanoparticles ofγ-Mnx Fe2-x O3 synthesized by a single step process.J Mater Chem,2007,17(48):5042-5051
[56]Lin FC,Hsu CH,Lin YY.Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins:insights from mathematical modeling.Int JNanomed,2018,13:3529-3539
[57]Huang H,Delikanli S,Zeng H,et al.Remote control of ion channels and neurons through magnetic-field heating of nanoparticles.Nat Nanotechnol,2010,5(8):602-606
[58]Chen R,Romero G,Christiansen MG,et al.Wireless magnetothermal deep brain stimulation.Science,2015,347(6229):1477-1480
[59]Stanley SA,Gagner JE,Damanpour S,et al.Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice.Science,2012,336(6081):604-608
[60]Stanley SA,Sauer J,Kane RS,et al.Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles.Nat Med,2015,21(1):92-98
[61]Stanley SA,Kelly L,Latcha KN,et al.Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism.Nature,2016,531(7596):647-650
[62]Cao Z,Wang D,Li Y,et al.Effect of nanoheat stimulation mediated by magnetic nanocomposite hydrogel on the osteogenic differentiation of mesenchymal stem cells.Sci China Life Sci,2018,61(4):448-456
[63]Moise S,Byrne JM,El Haj AJ,et al.The potential of magnetic hyperthermia for triggering the differentiation of cancer cells.Nanoscale,2018,10(44):20519-20525
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