基于氧化铁的磁性纳米颗粒在肿瘤诊疗中的应用进展
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摘要
将治疗性药物和成像组件集成于一个纳米平台内,构建兼具诊断和治疗功能的纳米颗粒(nanoparticles,NPs),实现肿瘤诊疗一体化是近年来纳米肿瘤学领域的研究热点。基于氧化铁(iron oxide,IO)的磁性纳米颗粒(magnetic nanoparticles,MNPs)是一种典型的诊治一体化性NPs,具有生物安全性高、超顺磁性及表面易于修饰和功能化等优点。MNPs不仅具有良好的载药能力,还具有T2W MR成像、磁靶向和磁热疗等功能,目前已广泛应用于肿瘤诊治一体化的研究中。本文对MNPs的结构,及其在肿瘤成像(T2W MRI成像联合T1W MRI、CT、光学、PET/SPECT和超声等双/多模态成像)以及肿瘤治疗[化疗、光动力治疗(photodynamic therapy,PDT)、光热治疗和磁热疗]等方面的研究进行综述。
Cancer theranostics has attracted increasing attention in the area of nanooncology, where the therapeutic drugs and diagnostic imaging are integrated into a multifunctional nanoplatform. A theranostic nanoparticle can deliver therapeutic drugs and imaging agents simultaneously. Iron oxide based magnetic nanoparticles(MNPs) are one of the most typical theranostic nanoparticles and have many excellent properties, such as biosafety, superparamagnetism, and tunable surface modifications and functionalizations.Moreover, they have drug loading capacity along with the distinctive properties of T2 weighted magnetic resonance imaging(T2 W MRI), magnetic targeting, and magnetic hyperthermia. Presently, iron oxide based MNPs are being widely used in cancer theranostic research. This paper introduces the general structure of iron oxide based MNPs and reviews their applications in cancer dual/multiple modal imaging(T2 W MRI combining T1 W MRI, CT, optical imaging, PET/SPECT, and ultrasound) and therapy(chemotherapy, photodynamic therapy, photothermal therapy, and magnetic hyperthermia).
Cancer theranostics has attracted increasing attention in the area of nanooncology, where the therapeutic drugs and diagnostic imaging are integrated into a multifunctional nanoplatform. A theranostic nanoparticle can deliver therapeutic drugs and imaging agents simultaneously. Iron oxide based magnetic nanoparticles(MNPs) are one of the most typical theranostic nanoparticles and have many excellent properties, such as biosafety, superparamagnetism, and tunable surface modifications and functionalizations.Moreover, they have drug loading capacity along with the distinctive properties of T2 weighted magnetic resonance imaging(T2 W MRI), magnetic targeting, and magnetic hyperthermia. Presently, iron oxide based MNPs are being widely used in cancer theranostic research. This paper introduces the general structure of iron oxide based MNPs and reviews their applications in cancer dual/multiple modal imaging(T2 W MRI combining T1 W MRI, CT, optical imaging, PET/SPECT, and ultrasound) and therapy(chemotherapy, photodynamic therapy, photothermal therapy, and magnetic hyperthermia).
引文
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[27]Song W,Luo Y,Zhao Y,et al.Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer:an in vitro study[J].Nanomedicine,2017,12(9):991-1009.
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[29]Bian R,Wang T,Zhang L,et al.A combination of tri-modal cancer imaging and in vivo drug delivery by metal-organic framework based composite nanoparticles[J].Biomater Sci,2015,3(9):1270-1278.
[30]Miao Z,Guo C,Li Z,et al.Fabrication of a multimodal microbubble platform for magnetic resonance,ultrasound and fluorescence imaging application[J].J Nanosci Nanotechnol,2016,16(3):2301-2306.
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[33]Ji F,Zhang K,Li J,et al.A dual pH/magnetic responsive nanocarrier based on PEGylated Fe3O4nanoparticles for doxorubicin delivery[J].JNanosci Nanotechnol,2018,18(7):4464-4470.
[34]Li E,Yang Y,Hao G,et al.Multifunctional magnetic mesoporous silica nanoagents for in vivo enzyme-responsive drug delivery and MRimaging[J].Nanotheranostics,2018,2(3):233-242.
[35]Semkina AS,Abakumov MA,Skorikov AS,et al.Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer[J].Nanomedicine,2018,14(5):1733-1742.
[36]Mfouo TI,Abrahamse H.Nano-Mmediated photodynamic therapy for cancer:enhancement of cancer specificity and therapeutic effects[J].Nanomaterials(Basel),2018,8(11):E923.
[37]Demian VS,Vida M,Henriette DB,et al.Oncologic photodynamic therapy:basic principles,current clinical status and future directions[J].Cancers,2017,9(12):19.
[38]Zhan J,Ma Z,Wang D,et al.Magnetic and p H dual-responsive mesoporous silica nanocomposites for effective and low-toxic photodynamic therapy[J].Int J Nanomedicine,2017,(12):2733-2748.
[39]Wenyan Y,Liang Y,Jie Y,et al.High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy[J].ACS Nano,2014,8(7):6922-6933.
[40]Suriyanto,Ng EYK,Kumar SD.Physical mechanism and modeling of heat generation and transfer in magnetic fluid hyperthermia through Néelian and Brownian relaxation:a review[J].Biom Eng Online,2017,16(1):36.
[41]Klaus MH,Frank U,Dirk N,et al.Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme[J].J Neurooncol,2011,103(2):317-324.
[42]Mahmoudi K,Bouras A,Bozec D,et al.Magnetic hyperthermia therapy for the treatment of glioblastoma:a review of the therapy's history,efficacy and application in humans[J].Int J Hyperthermia,2018,34(8):1316-1328.
[43]Hurley KR,Ring H,Etheridge ML,et al.Predictable heating and positive MRI contrast from a mesoporous silica-coated iron oxide nanoparticle[J].Mol Pharm,2016,13(7):2172-2183.
[44]Arriortua OK,Insausti M,Lezama L,et al.RGD-Functionalized Fe3O4Nanoparticles for Magnetic Hyperthermia[J].Colloids Surf B Biointerfaces,2018,(165):315-324.
[2]Li C.A targeted approach to cancer imaging and therapy[J].Nat Mater,2014,13(2):110-115.
[3]Sharma R,Mody N,Agrawal U,et al.Theranostic nanomedicine;a next generation platform for cancer diagnosis and therapy[J].Mini Rev Med Chem,2017,17(18):1746-1757.
[4]Mohammadi A,Barikani M,Barmar M.Effect of surface modification of Fe3O4nanoparticles on thermal and mechanical properties of magnetic polyurethane elastomer nanocomposites[J].J Mater Sci,2013,48(21):7493-7502.
[5]Kang T,Li F,Baik S,et al.Surface design of magnetic nanoparticles for stimuli-responsive cancer imaging and therapy[J].Biomaterials,2017,(136):98-114.
[6]Zhu N,Ji H,Yu P,et al.Surface modification of magnetic iron oxide nanoparticles[J].Nanomaterials,2018,8(10):810.
[7]Cardoso VF,Francesko António,Ribeiro C,et al.Advances in magnetic nanoparticles for biomedical applications[J].Adv Healthc Mater,2018,7(5):201700845.
[8]Mosayebi J,Kiyasatfar M,Laurent S.Synthesis,functionalization,and design of magnetic nanoparticles for theranostic applications[J].Adv Healthc Mater,2017,6(23):201700306.
[9]Li X,Wei J,Aifantis KE,et al.Current investigations into magnetic nanoparticles for biomedical applications[J].J Biomed Mater Res A,2016,104(5):1285-1296.
[10]Karpuz M,Silindir-Gunay M,Ozer AY.Current and future approaches for effective cancer imaging and treatment[J].Cancer Biother and Radiopharm,2018,33(2):39-51.
[11]Li X,Kim J,Yoon J,et al.Cancer-associated,stimuli-driven,turn on theranostics for multimodality imaging and therapy[J].Adv Mater,2017,29(23):201606857.
[12]Yang H,Zhuang Y,Sun Y,et al.Targeted dual-contrast T1-and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles[J].Biomaterials,2011,32(20):4584-4593.
[13]Zeng Y,Wang L,Zhou Z,et al.Gadolinium hybrid iron oxide nanocomposites for dual T1-and T2-weighted MR imaging of cell labeling[J].Biomater Sci,2016,5(1):50-56.
[14]Xiao N,Gu W,Wang H,et al.T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles[J].J Colloid Interface Sci,2014,(417):159-165.
[15]Huang X,Yuan Y,Ruan W,et al.p H-responsive theranostic nanocomposites as synergistically enhancing positive and negative magnetic resonance imaging contrast agents[J].J Nanobiotechnology,2018,16(1):30.
[16]Li J,Hu Y,Yang J,et al.Hyaluronic acid-modified Fe3O4@Au core/shell nanostars for multimodal imaging and photothermal therapy of tumors[J].Biomaterials,2015,(38):10-21.
[17]S R,M P.Multi-functional core-shell Fe3O4@Au nanoparticles for cancer diagnosis and therapy[J].Colloids Surf B Biointerfaces,2019,(174):252-259.
[18]Tseng YJ,Chou SW,Shyue JJ,et al.A versatile theranostic delivery platform integrating magnetic resonance imaging/computed tomography,p H/cis-Diol controlled release,and targeted therapy[J].Acs Nano,2016,10(6):5809-5822.
[19]Yang G,Gong H,Liu T,et al.Two-dimensional magnetic WS2@Fe3O4nanocomposite with mesoporous silica coating for drug delivery and imaging-guided therapy of cancer[J].Biomaterials,2015,(60):62-71.
[20]Badrigilan S,Shaabani B,Gharehaghaji N,et al.Iron oxide/bismuth oxide nanocomposites coated by graphene quantum dots:"three-inone"theranostic agents for simultaneous CT/MR imaging-guided in vitro photothermal therapy[J].Photodiagnosis Photodyn Ther,2019,(25):504-514.
[21]Santra S,Kaittanis C,Grimm J,et al.Drug/dye-loaded,multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging[J].Small,2009,5(16):1862-1868.
[22]Zhou Q,Mu K,Jiang L,et al.Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging[J].Int J Nanomedicine,2015,(10):1805-1818.
[23]Ai F,Ferreira CA,Chen F,et al.Engineering of radiolabeled iron oxide nanoparticles for dual-modality imaging[J].Wiley Interdiscip Rev Nano Nanobiotechnol,2016,8(4):619-630.
[24]Chen J,Zhu S,Tong L,et al.Superparamagnetic iron oxide nanoparticles mediated131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice[J].BMC Cancer,2014,14(1):114.
[25]Doughton JA,Hofman MS,Eu P,et al.A first-in-human study of 68Gananocolloid PET/CT sentinel lymph node imaging in prostate cancer demonstrates aberrant lymphatic drainage pathways[J].J Nucl Med,2018,59(12):1837-1842.
[26]Guo H,Jiang Z,Song S,et al.Structural regulation of self-assembled iron oxide/polymer microbubbles towards performance-tunable magnetic resonance/ultrasonic dual imaging agents[J].J Colloid Interface Sci,2016,(482):95-104.
[27]Song W,Luo Y,Zhao Y,et al.Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer:an in vitro study[J].Nanomedicine,2017,12(9):991-1009.
[28]Feng LL,Yang D,He F,et al.A core-shell-satellite structured Fe3O4@gC3N4-UCNPs-PEG for T-1/T-2-weighted dual-modal MRI-guided photodynamic therapy[J].Adv Healthc Mater,2017,6(18):13.
[29]Bian R,Wang T,Zhang L,et al.A combination of tri-modal cancer imaging and in vivo drug delivery by metal-organic framework based composite nanoparticles[J].Biomater Sci,2015,3(9):1270-1278.
[30]Miao Z,Guo C,Li Z,et al.Fabrication of a multimodal microbubble platform for magnetic resonance,ultrasound and fluorescence imaging application[J].J Nanosci Nanotechnol,2016,16(3):2301-2306.
[31]El-Boubbou K.Magnetic iron oxide nanoparticles as drug carriers:preparation,conjugation and delivery[J].Nanomedicine(London),2018,13(8):929-952.
[32]Xiong F,Huang S,Gu N.Magnetic nanoparticles:recent developments in drug delivery system[J].Drug Dev Ind Pharm,2018,44(5):697-706.
[33]Ji F,Zhang K,Li J,et al.A dual pH/magnetic responsive nanocarrier based on PEGylated Fe3O4nanoparticles for doxorubicin delivery[J].JNanosci Nanotechnol,2018,18(7):4464-4470.
[34]Li E,Yang Y,Hao G,et al.Multifunctional magnetic mesoporous silica nanoagents for in vivo enzyme-responsive drug delivery and MRimaging[J].Nanotheranostics,2018,2(3):233-242.
[35]Semkina AS,Abakumov MA,Skorikov AS,et al.Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer[J].Nanomedicine,2018,14(5):1733-1742.
[36]Mfouo TI,Abrahamse H.Nano-Mmediated photodynamic therapy for cancer:enhancement of cancer specificity and therapeutic effects[J].Nanomaterials(Basel),2018,8(11):E923.
[37]Demian VS,Vida M,Henriette DB,et al.Oncologic photodynamic therapy:basic principles,current clinical status and future directions[J].Cancers,2017,9(12):19.
[38]Zhan J,Ma Z,Wang D,et al.Magnetic and p H dual-responsive mesoporous silica nanocomposites for effective and low-toxic photodynamic therapy[J].Int J Nanomedicine,2017,(12):2733-2748.
[39]Wenyan Y,Liang Y,Jie Y,et al.High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy[J].ACS Nano,2014,8(7):6922-6933.
[40]Suriyanto,Ng EYK,Kumar SD.Physical mechanism and modeling of heat generation and transfer in magnetic fluid hyperthermia through Néelian and Brownian relaxation:a review[J].Biom Eng Online,2017,16(1):36.
[41]Klaus MH,Frank U,Dirk N,et al.Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme[J].J Neurooncol,2011,103(2):317-324.
[42]Mahmoudi K,Bouras A,Bozec D,et al.Magnetic hyperthermia therapy for the treatment of glioblastoma:a review of the therapy's history,efficacy and application in humans[J].Int J Hyperthermia,2018,34(8):1316-1328.
[43]Hurley KR,Ring H,Etheridge ML,et al.Predictable heating and positive MRI contrast from a mesoporous silica-coated iron oxide nanoparticle[J].Mol Pharm,2016,13(7):2172-2183.
[44]Arriortua OK,Insausti M,Lezama L,et al.RGD-Functionalized Fe3O4Nanoparticles for Magnetic Hyperthermia[J].Colloids Surf B Biointerfaces,2018,(165):315-324.