超声微泡介导靶向治疗研究进展
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摘要
载药超声微泡的靶向治疗是当前医药领域中的研究热点。超声微泡破坏技术介导的靶向药物和基因治疗是一种最新的靶向治疗方法。超声微泡不仅可以作为一种超声造影剂增强成像对比度,更可以通过各种物理、化学修饰携带各种药物或基因在超声场强破坏作用下进行靶向治疗。超声微泡造影剂靶向治疗包括超声介导载药微泡的治疗及超声介导靶向载药微泡的治疗。本文就超声微泡特性、超声靶向微泡破坏(UTMD)技术机制、超声微泡介导靶向治疗三方面进行综述。
Drug loaded microbubble mediated target therapy is one of the research hotspot in medicine.Ultrasound-targeted drug and gene loaded microbubbles destruction(UTMD)is a newest strategy for target therapy.Ultrasound microbubbles not only can be used as ultrasound contrast agent to enhance imaging contrast,but also can be used to carry different drugs or genes for target therapy when destroyed by ultrasound irradiation through a variety of physical and chemical modifications.Ultrasound microbubble contrast agent targeted therapy includes ultrasound mediated microbubble therapy and ultrasound mediated targeted microbubble therapy.The properties of ultrasound microbubbles,the mechanism of UTMD technology,the application of targeted therapy mediate by ultrasound microbubbles contrast enhancement were reviewed in this paper.
Drug loaded microbubble mediated target therapy is one of the research hotspot in medicine.Ultrasound-targeted drug and gene loaded microbubbles destruction(UTMD)is a newest strategy for target therapy.Ultrasound microbubbles not only can be used as ultrasound contrast agent to enhance imaging contrast,but also can be used to carry different drugs or genes for target therapy when destroyed by ultrasound irradiation through a variety of physical and chemical modifications.Ultrasound microbubble contrast agent targeted therapy includes ultrasound mediated microbubble therapy and ultrasound mediated targeted microbubble therapy.The properties of ultrasound microbubbles,the mechanism of UTMD technology,the application of targeted therapy mediate by ultrasound microbubbles contrast enhancement were reviewed in this paper.
引文
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[21]SUGANO M,NEGISHI Y,ENDO-TAKAHASHI Y,et al.Gene delivery system involving Bubble liposomes and ultrasound for the efficient in vivo delivery of genes into mouse tongue tissue[J].Int J Pharm,2012,422(1/2):332-337.
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[23]INOUE H,ARAI Y,KISHIDA T,et al.Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis using 3MHz pulsed ultrasound[J].Ultrasonics,2014,54(3):874-881.
[24]HAO Y,GUO L,ABUDULA A,et al.Proliferation inhibition and apoptosis enhancement of human cervical cancer cells by ultrasound-targeted microbubble destruction delivered double suicide genes[J].Int J Clin Exp Med,2014,7(12):5330-5335.
[25]ABDAIKADER R,KAWAKAMI S,UNGA J,et al.Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model[J].Acta Biomater,2015,19:112-118.
[26]MENG X M,NIKOLIC-PATERSON D J,LAN H Y.TGF-βthe master regulator of fibrosis[J].Nat Rev Nephrol,2016,12(6):325-338.
[27]KA S M,YEH Y C,HUANG X R,et al.Kidney-targeting Smad7gene transfer inhibits renal TGF-β/MAD homologue(SMAD)and nuclear factorκB(NF-κB)signalling pathways,and improves diabetic nephropathy in mice[J].Diabetologia,2012,55(2):509-519.
[28]LIU GX,LI YQ,HUANG X R,et al.Smad7inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension[J].Clin Sci(Lond),2014,127(3):195-208.
[29]李佩倞.超声联合微泡促HGF修饰BMSCs靶向归巢抗肾纤维化的实验研究[D].重庆:第三军医大学,2013.
[30]田新桥,茹翱,赵应征,等.超声微泡靶向递送aFGF对糖尿病心肌病的治疗作用及其机制研究[J].中国病理生理杂志,2013,29(8):1387-1392.
[31]MOZAFARI M,SHIMODA M,URBANSKA A M,et al.Ultrasoundtargeted microbubble destruction:toward a new strategy for diabetes treatment[J].Drug Discov Today,2016,21(4):540-543.
[2]WALLACE N,WRENN S P.Ultrasound triggered drug delivery with liposomal nested microbubbles[J].Ultrasonics,2015,63:31-38.
[3]MOON H,YOON C,LEE TW,et al.Therapeutic Ultrasound Contrast Agents for the Enhancement of Tumor Diagnosis and Tumor Therapy[J].J Biomed Nanotechnol.2015,11(7):1183-1192.
[4]胡劼.新型多聚体微泡携带药物舒尼替尼靶向治疗肾细胞癌的离体和在体实验研究[D].西安:第四军医大学,2013.
[5]YANG P S,TUNG F I,CHEN H P,et al.A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality[J].Acta Biomater,2014,10(8):3762-3774.
[6]LAMMERTINK B,DECKERS R,STORM G,et al.Duration of ultrasound-mediated enhanced plasma membrane permeability[J].Int J Pharm,2015,482(1/2):92-98.
[7]周永昌,郭万学.超声医学[M].北京:人民军医出版社,2015:1622.
[8]BAZAN-PEREGRINO M,RIFAI B,CARLISLE R C,et al.Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound[J].J Control Release,2013,169(1/2):40-47.
[9]WOOD A K,SEHGAL C M.A review of low-intensity ultrasound for cancer therapy[J].Ultrasound Med Biol,2015,41(4):905-928.
[10]SKACHKOV I,LUAN Y,VAN DER STEEN A F,et al.Targeted microbubble mediated sonoporation of endothelial cells in vivo[J].IEEE Trans Ultrason Ferroelectr Freq Control,2014,61(10):1661-1667.
[11]YOON Y I,YOON T J,LEE H J,et al.Optimization of ultrasound parameters for microbubble-nanoliposome complex-mediated delivery[J].Ultrasonography,2015,34(4):297-303.
[12]DELALANDE A,BUREAU MF,MIDOUX P,et al.Ultrasound-assisted microbubbles gene transfer in tendons for gene therapy[J].Ultrasonics,2010,50(2):269-272.
[13]SHI F,YANG F,HE X,et al.Inhibitory effect of epirubicin-loaded lipid microbubbles with conjugated anti-ABCG2antibody combined with therapeutic ultrasound on multiple myeloma cancer stem cells[J].J Drug Target,2015,23:1-13.
[14]KWEKKEBOOM R F,SLUIJTER J P,VAN MIDDELAAR B,et al.Increased local delivery of antagomir therapeutics to the rodent myocardium using ultrasound and microbubbles[J].J Control Release,2015,11:20.
[15]ZHANG L,SUN Z,REN P,et al.Ultrasound-targeted microbubble destruction(UTMD)assisted delivery of shRNA against PHD2into H9C2Cells[J].PLoS One,2015,10(8):e0134629.
[16]KULIZEWSKI M A,KOBULNIK J,LINDNER J R,et al.Vascular gene transfer of SDF-1promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle[J].Mol Ther,2011,19(5):895-902.
[17]XU Y,XIE Z,ZHOU Y,et al.Experimental endostatin-GFP gene transfection into human retinal vascular endothelial cells using ultrasound-targeted cationic microbubble destruction[J].Mol Vis,2015,21:930-938.
[18]NEDERHOED J H,SLIKKERVEER J,MEYER K W,et al.Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock[J].Lab Anim(NY),2014,43(3):91-94.
[19]EBBEN H P,NEDERHOED J H,SLIKKERVEER J,et al.Therapeutic application of contrast-enhanced ultrasound and low-dose urokinase for thrombolysis in a porcine model of acute peripheral arterial occlusion[J].J Vasc Surg,2015,62(2):477-485.
[20]SUTTON J T,IVANCEVICH N M,PERRIN S R Jr,et al.Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an exvivo porcine thrombosis model[J].Ultrasound Med Biol,2013,39(5):813-824.
[21]SUGANO M,NEGISHI Y,ENDO-TAKAHASHI Y,et al.Gene delivery system involving Bubble liposomes and ultrasound for the efficient in vivo delivery of genes into mouse tongue tissue[J].Int J Pharm,2012,422(1/2):332-337.
[22]FLORINAS S,KIM J,NAM K,et al.Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment[J].J Control Release,2014,183:1-8.
[23]INOUE H,ARAI Y,KISHIDA T,et al.Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis using 3MHz pulsed ultrasound[J].Ultrasonics,2014,54(3):874-881.
[24]HAO Y,GUO L,ABUDULA A,et al.Proliferation inhibition and apoptosis enhancement of human cervical cancer cells by ultrasound-targeted microbubble destruction delivered double suicide genes[J].Int J Clin Exp Med,2014,7(12):5330-5335.
[25]ABDAIKADER R,KAWAKAMI S,UNGA J,et al.Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model[J].Acta Biomater,2015,19:112-118.
[26]MENG X M,NIKOLIC-PATERSON D J,LAN H Y.TGF-βthe master regulator of fibrosis[J].Nat Rev Nephrol,2016,12(6):325-338.
[27]KA S M,YEH Y C,HUANG X R,et al.Kidney-targeting Smad7gene transfer inhibits renal TGF-β/MAD homologue(SMAD)and nuclear factorκB(NF-κB)signalling pathways,and improves diabetic nephropathy in mice[J].Diabetologia,2012,55(2):509-519.
[28]LIU GX,LI YQ,HUANG X R,et al.Smad7inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension[J].Clin Sci(Lond),2014,127(3):195-208.
[29]李佩倞.超声联合微泡促HGF修饰BMSCs靶向归巢抗肾纤维化的实验研究[D].重庆:第三军医大学,2013.
[30]田新桥,茹翱,赵应征,等.超声微泡靶向递送aFGF对糖尿病心肌病的治疗作用及其机制研究[J].中国病理生理杂志,2013,29(8):1387-1392.
[31]MOZAFARI M,SHIMODA M,URBANSKA A M,et al.Ultrasoundtargeted microbubble destruction:toward a new strategy for diabetes treatment[J].Drug Discov Today,2016,21(4):540-543.