靶向超声微泡在肝癌治疗领域的研究进展
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摘要
在临床上现有的肝癌治疗方法为手术切除、射频消融、动脉栓塞化疗、无水酒精瘤内注射及肝移植等。靶向超声微泡的出现,拓展了传统肝癌的治疗思路,它不仅具有无创伤、无痛苦、无辐射、易重复使用的优点,还为药物和基因的靶向释放提供技术支持,并可以明显增强现有治疗方法的效果,在肝癌治疗方面展示出十分诱人的前景。本文就目前靶向超声微泡在肝癌治疗领域的机制与应用,以及存在的局限性和发展做一综述。
Liver cancer,which has a high incidence,is one of the common malignant tumors in our country. The existing clinical treatments are surgical resection,radiofrequency ablation,liver transplantation,etc. The advent of ultrasound targeted microbubbles expands the traditional idea of liver cancer treatment and it has the advantages of no trauma,no pain,no radiation,and easy to repeated. This new technique provides technical support for targeted release of drugs and genes,and significantly enhances the effectiveness of existing treatments,which demonstrate attractive prospects in the treatment of liver cancer. In this paper,we present an overview of the mechanism and applications of ultrasound targeted microbubbles in the treatment of liver cancer,as well as its limitations and development.
Liver cancer,which has a high incidence,is one of the common malignant tumors in our country. The existing clinical treatments are surgical resection,radiofrequency ablation,liver transplantation,etc. The advent of ultrasound targeted microbubbles expands the traditional idea of liver cancer treatment and it has the advantages of no trauma,no pain,no radiation,and easy to repeated. This new technique provides technical support for targeted release of drugs and genes,and significantly enhances the effectiveness of existing treatments,which demonstrate attractive prospects in the treatment of liver cancer. In this paper,we present an overview of the mechanism and applications of ultrasound targeted microbubbles in the treatment of liver cancer,as well as its limitations and development.
引文
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[23]Liu XL,Yang Q,Gao QQ,et al.Experimental study of the impact of cavitation of microbubbles combined with prothrombin on blocking regional hepatic micrangium in rabbits[J].Chin J Ultrasound in Med,2015,31(04):369-372.
[24]Kang J,Wu XL,Zhang Y,et al.Effect of docetaxel-loaded lipid microbubbles combined with ultrasound targeted microbubbles destruction on microvessel of rabbit VX2 liver tumor models[J].Chin J Interventional Imaging and Therapy,2011,8(5):431-434.
[25]Qian LX,Wei HT,Hu XD.Current situation and progress of local ablation therapy forhepatocellular carcinoma[J].World Chin J Digestol,2008,16(18):1955-1961.
[26]Chen C.Effect of microbubble ultrasound contrast agents in high intensity focused ultrasound treatment of solid tumors[J].J Modern Med Health,2016,32(3):398-400.
[27]He W,Wang W,Peng S.Microbubbles enhanced HIFU ablation on rabbit hepatic VX2 tumors:detecting residual tumor with contrast-enhanced ultrasound and spiral CT[J].J Zhejiang University(Medical Sciences),2013,42(3):337-344.
[28]Yoshizawa S,Matsuura K,Takagi R,et al.Detection of tissue coagulation by decorrelation of ultrasonic echo signals in cavitation-enhanced high-intensity focused ultrasound treatment[J].J Ther Ultrasound,2016,4:15.
[29]Liu Q,Wu SZ,Gao YJ,et al.Impact of acoustic cavitation disrupting on hepatic blood perfusion in rabbtis[J].Chin J Med Imaging Technol,2012,28(8):1440-1444.
[30]Hayashida K,Ooi J,Omagari K,et al.Percutaneous ethanol injection therapy by ethanol mixed with CO2 microbubble for hepatocellular carcinoma][J].Nihon Shokakibyo Gakkai Zasshi,1997,94(11):730-738.
[31]Gao W,Qiao L,Gao Y,et al.Effect of microbubble-enhanced ultrasound on percutaneous ethanol ablation of rat walker-256tumour[J].Eur Radiol,2016,26(9):3017-3025.
[32]Zhi-Yi Chen,Yan Lin,Feng Yang,et al.Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles[J].Cardiovasc Ultrasound,2013(11):11.
[2]Yang MJ,Wang LF,Guo YL,et al.In vivo and in vitro study of nanoscale microbubbles with G250 monoclonal antibodies targeting to renal cell carcinoma[J].J Third Military Medical University,2016,38(2):112-117.
[3]Yang YN,Gao YH,Tang KB,et al.Targeting RGDS-mediated liposome ultrasound contrast agent:preparation and prelmi inary in vitro study[J].J Third Military Medical University,2006,28(06):562-564.
[4]Yao M,Yao DF,Bian YZ,et al.Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma[J].Hepatobiliary Pancreat Dis Int,2011,10(3):289-294.
[5]Jing ZH,He CJ,Pan WL,et al.Preparation of nanoscale lipid microbubbles modified with hepatoma glypican 3 antibody and targeting study in vitro[J].J Chongqing Med University,2013,38(5):449-453.
[6]Shashank Sirsi,Mark Borden.State-of-the-art materials for ultrasound-triggered drug delivery[J].Adv Drug Deliv Rev,2014,1:3-14.
[7]Kang J,Wu XL,Zhang DZ,et al.Influence of docetaxel-loaded lipid microbubbles combined with ultrasound targeted microbubbles destruction on proliferation and apoptosis of hepatocellular carcinoma cell[J].J Chongqing Med University,2014,39(12):1698-1702.
[8]Wang X,Ran HT,Wang ZG,et al.New type of drug-loaded microbubbles combine with ultrasound targeted microbblues destruction for treatment of rabbit VX2 liver cancer[J].Chin J Med Imaging Technol,2013,29(4):484-488.
[9]Zhu F,Jiang Y,Luo F,et al.Effectiveness of localized ultrasoundtargeted microbubble destruction with doxorubicin liposomes in H22mouse hepatocellular carcinoma model[J].J Drug Target,2015,23(4):323-334.
[10]Zhang XJ,Ke LM,Yang J,et al.Preparation and characterization of hepatocyte-targeting liposome containing hydroxycamptothecin Chinese[J].J Tissue Engineering Res,2012,16(34):6339-6342.
[11]Alter J,Sennoga CA,Lopes DM,et al.Microbubble st ability is a major determinant of the efficiency of ultrasound and microbubble mediated in vivo gene transfer[J].Ultrasound Med Biol,2009,35(6):976-984.
[12]Xue Y,Yang G,Wang C,et al.Effects of shRNA-mediated SOX9 inhibition on cell proliferation and apoptosis in human HCC cell line hep3b mediated by ultrasound-targeted microbubble destruction(UTMD)[J].Cell Biochem Biophys,2015,73(2):553-558.
[13]Xiang X,Tang Y,Leng Q,et al.Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo[J].Ultrasonics,2016,65:304-314.
[14]Jing H,Cheng W,Zhang JW,et al.Galactosylated poly-L-lysine targeted microbubbles for ultrasound mediated antisense cmyc gene transfection in hepatocellular carcinoma cells[J].Arch Med Sci,2015,11(2):292-300.
[15]Lawrie A,Brisken AF,Francis SE,et al.Microbubble enhanced ultrasound for vascular gene delivery[J].Gene Therapy,2000,7(23):2023-2027.
[16]Wang ZH,Zhang HY,Xia ZT,et.al.Inhibition of expression of JKNlin mouse hepatocellular carcinoma cell lines and cell migration and invasion mediated by ultrasound-targeted microbubble destruction[J].J Jilin University(Medicine Edition),2015,41(1):21-26.
[17]Chertok B,Langer R,Anderson DG.Spatial control of gene expression by nanocarriers using heparin masking and ultrasoundtargeted microbubble destruction[J].ACS Nano,2016,5:12.
[18]Li HY,Zhou SJ,Liu CA,et al.Effects of ultrasound-targeted microbubbles encapsulating HSV1-TK gene in nude mice hepatocellular carcinoma after HIFU treatment[J].J China Med University,2013,42(1):31-37.
[19]Li J,Zhou P,Li L,et al.Effects of cationic microbubble carrying CD/TK double suicide gene and alphavbeta3 integrin antibody in human hepatocellular carcinoma Hep G2 cells[J].PLo S One,2016,11(7):e158592.
[20]Li GJ,Yang L,Shi XL,et al.Relationship between morphological characteristics of tumor microvessel and biological features of primary hepatocellular carcinoma[J].World Chin J Digestol,2005,13(13):1503-1506.
[21]Sun T,Samiotaki G,Wang S,et al.Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening[J].Phys Med Biol,2015,60(23):9079-9094.
[22]Zhong Y,Liu Z.Pathological changes of tumor microcirculation obstruction bymicrobubbles mediated ultrasound cavitation[J].Chin J Med Imaging Technol,2015,31(8):1131-1134.
[23]Liu XL,Yang Q,Gao QQ,et al.Experimental study of the impact of cavitation of microbubbles combined with prothrombin on blocking regional hepatic micrangium in rabbits[J].Chin J Ultrasound in Med,2015,31(04):369-372.
[24]Kang J,Wu XL,Zhang Y,et al.Effect of docetaxel-loaded lipid microbubbles combined with ultrasound targeted microbubbles destruction on microvessel of rabbit VX2 liver tumor models[J].Chin J Interventional Imaging and Therapy,2011,8(5):431-434.
[25]Qian LX,Wei HT,Hu XD.Current situation and progress of local ablation therapy forhepatocellular carcinoma[J].World Chin J Digestol,2008,16(18):1955-1961.
[26]Chen C.Effect of microbubble ultrasound contrast agents in high intensity focused ultrasound treatment of solid tumors[J].J Modern Med Health,2016,32(3):398-400.
[27]He W,Wang W,Peng S.Microbubbles enhanced HIFU ablation on rabbit hepatic VX2 tumors:detecting residual tumor with contrast-enhanced ultrasound and spiral CT[J].J Zhejiang University(Medical Sciences),2013,42(3):337-344.
[28]Yoshizawa S,Matsuura K,Takagi R,et al.Detection of tissue coagulation by decorrelation of ultrasonic echo signals in cavitation-enhanced high-intensity focused ultrasound treatment[J].J Ther Ultrasound,2016,4:15.
[29]Liu Q,Wu SZ,Gao YJ,et al.Impact of acoustic cavitation disrupting on hepatic blood perfusion in rabbtis[J].Chin J Med Imaging Technol,2012,28(8):1440-1444.
[30]Hayashida K,Ooi J,Omagari K,et al.Percutaneous ethanol injection therapy by ethanol mixed with CO2 microbubble for hepatocellular carcinoma][J].Nihon Shokakibyo Gakkai Zasshi,1997,94(11):730-738.
[31]Gao W,Qiao L,Gao Y,et al.Effect of microbubble-enhanced ultrasound on percutaneous ethanol ablation of rat walker-256tumour[J].Eur Radiol,2016,26(9):3017-3025.
[32]Zhi-Yi Chen,Yan Lin,Feng Yang,et al.Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles[J].Cardiovasc Ultrasound,2013(11):11.