Abstract
The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.
概 要
随着超声影像新技术的不断发展和超声造影剂制 备技术的不断改进, 低频超声和超声造影剂在肿 瘤治疗中的作用日趋重要。利用超声波与微泡造影剂的相互作用及所产生的生物学效应, 可实现微泡携的基因、药物等向靶目标组织的转移释放, 介导肿瘤细胞的凋亡及肿瘤微血管的栓塞阻断等, 从而起到靶向治疗的作用。随着超声波参数的优化和靶向微泡造影剂的研制, 以及各种兼具诊治功能的复合型应用探头的面世, 低频超声联合微泡造影剂介导肿瘤靶向治疗将为临床肿瘤的治疗带来新的希望。
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References
Bai WK, Zhang W, Hu B, et al., 2016. Liposome-mediated transfection of wild-type P53 DNA into human prostate cancer cells is improved by low-frequency ultrasound combined with microbubbles. Oncol Lett, 11(6):3829–3834. https://doi.org/10.3892/ol.2016.4477
Delalande A, Bastié C, Pigeon L, et al., 2017. Cationic gas-filled microbubbles for ultrasound-based nucleic acids delivery. Biosci Rep, 37(6):BSR20160619. https://doi.org/10.1042/BSR20160619
Feng R, 2004. Ultrasound cavitation and ultrasound medicine. Chin J Ultrasonogr, 13(1):63–65 (in Chinese).
Gangeh MJ, Hashim A, Giles A, et al., 2016. Computer aided prognosis for cell death categorization and prediction in vivo using quantitative ultrasound and machine learning techniques. Med Phys, 43(12):6439–6454. https://doi.org/10.1118/1.4967265
Gramiak R, Shah PM, 1968. Echocardiography of the aortic root. Invest Radiol, 3(5):356–366.
Grieser F, Choi PK, Enomoto N, et al., 2015. Sonochemistry and the Acoustic Bubble. Elsevier, Amsterdam, The Netherlands, p.41–83. https://doi.org/10.1016/C2013-0-18886-1
Hodnett M, Zeqiri B, 2008. Toward a reference ultrasonic cavitation vessel: Part 2: investigating the spatial variation and acoustic pressure threshold of inertial cavitation in a 25 kHz ultrasound field. IEEE Trans Ultrason Ferroelectr Freq Control, 55(8):1809–1822. https://doi.org/10.1109/TUFFC.2008.864
Hou R, Xu YJ, Lu QJ, et al., 2017. Effect of low-frequency low-intensity ultrasound with microbubbles on prostate cancer hypoxia. Tumour Biol, 39(10):1010428317719275. https://doi.org/10.1177/1010428317719275
Ji YL, Han Z, Shao LM, et al., 2016. Evaluation of in vivo antitumor effects of low-frequency ultrasound-mediated miRNA-133a microbubble delivery in breast cancer. Cancer Med, 5(9):2534–2543. https://doi.org/10.1002/cam4.840
Lagneaux L, de Meulenaer EC, Delforge A, et al., 2002. Ultrasonic low-energy treatment: a novel approach to induce apoptosis in human leukemic cells. Exp Hematol, 30(11): 1293–1301. https://doi.org/10.1016/S0301-472X(02)00920-7
Lavon I, Kost J, 2004. Ultrasound and transdermal drug delivery. Drug Discov Today, 9(15):670–676. https://doi.org/10.1016/S1359-6446(04)03170-8
Li QY, Li HY, He CJ, et al., 2017. The use of 5-fluorouracilloaded nanobubbles combined with low-frequency ultrasound to treat hepatocellular carcinoma in nude mice. Eur J Med Res, 22:48. https://doi.org/10.1186/s40001-017-0291-8
Lin HY, Chen JF, Chen CP, 2016. A novel technology: microfluidic devices for microbubble ultrasound contrast agent generation. Med Biol Eng Comput, 54(9):1317–1330. https://doi.org/10.1007/s11517-016-1475-z
Lin L, Baehrecke EH, 2015. Autophagy, cell death, and cancer. Mol Cell Oncol, 2(3):e985913. https://doi.org/10.4161/23723556.2014.985913
Mariglia J, Momin S, Coe IR, et al., 2018. Analysis of the cytotoxic effects of combined ultrasound, microbubble and nucleoside analog combinations on pancreatic cells in vitro. Ultrasonics, 89:110–117. https://doi.org/10.1016/j.ultras.2018.05.002
Moon H, Kang J, Sim C, et al., 2015a. Multifunctional theranostic contrast agent for photoacoustics- and ultrasound-based tumor diagnosis and ultrasound-stimulated local tumor therapy. J Control Release, 218:63–71. https://doi.org/10.1016/j.jconrel.2015.09.060
Moon H, Yoon C, Lee TW, et al., 2015b. Therapeutic ultrasound contrast agents for the enhancement of tumor diagnosis and tumor therapy. J Biomed Nanotechnol, 11(7): 1183–1192. https://doi.org/10.1166/jbn.2015.2056
Mulvana H, Browning RJ, Luan Y, et al., 2017. Characterization of contrast agent microbubbles for ultrasound imaging and therapy research. IEEE Trans Ultrason Ferroelectr Freq Control, 64(1):232–251. https://doi.org/10.1109/TUFFC.2016.2613991
Nguyen TT, Asakura Y, Koda S, et al., 2017. Dependence of cavitation, chemical effect, and mechanical effect thresholds on ultrasonic frequency. Ultrason Sonochem, 39:301–306. https://doi.org/10.1016/j.ultsonch.2017.04.037
Pétrier C, Francony A, 1997. Ultrasonic waste-water treatment: incidence of ultrasonic frequency on the rate of phenol and carbon tetrachloride degradation. Ultrason Sonochem, 4(4):295–300. https://doi.org/10.1016/S1350-4177(97)00036-9
Qian LJ, Thapa B, Hong J, et al., 2018. The present and future role of ultrasound targeted microbubble destruction in preclinical studies of cardiac gene therapy. J Thorac Dis, 10(2):1099–1111. https://doi.org/10.21037/jtd.2018.01.101
Rebecca VW, Amaravadi RK, 2016. Emerging strategies to effectively target autophagy in cancer. Oncogene, 35(1): 1–11. https://doi.org/10.1038/onc.2015.99
Ren ST, Liao YR, Kang XN, et al., 2013. The antitumor effect of a new docetaxel-loaded microbubble combined with low-frequency ultrasound in vitro: preparation and parameter analysis. Pharm Res, 30(6):1574–1585. https://doi.org/10.1007/s11095-013-0996-5
Ren ST, Shen S, He XY, et al., 2016. The effect of docetaxel-loaded micro-bubbles combined with low-frequency ultrasound in H22 hepatocellular carcinoma-bearing mice. Ultrasound Med Biol, 42(2):549–560. https://doi.org/10.1016/j.ultrasmedbio.2015.10.008
Sadeghi-Naini A, Stanisz M, Tadayyon H, et al., 2016. Low-frequency ultrasound radiosensitization and therapy response monitoring of tumors: an in vivo study. Proc 38th Annual Int Conf of the IEEE Engineering in Medicine and Biology Society, p.3227–3230. https://doi.org/10.1109/EMBC.2016.7591416
Schutt EG, Klein DH, Mattrey RM, et al., 2003. Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals. Angew Chem Int Ed Engl, 42(28):3218–3235. https://doi.org/10.1002/anie.200200550
Shen YY, Pi ZK, Yan F, et al., 2017. Enhanced delivery of paclitaxel liposomes using focused ultrasound with microbubbles for treating nude mice bearing intracranial glioblastoma xenografts. Int J Nanomed, 12:5613–5629. https://doi.org/10.2147/IJN.S136401
Shen ZY, Shen E, Zhang JZ, et al., 2013. Effects of low-frequency ultrasound and microbubbles on angiogenesis-associated proteins in subcutaneous tumors of nude mice. Oncol Rep, 30(2):842–850. https://doi.org/10.3892/or.2013.2492
Shen ZY, Shen E, Diao XH, et al., 2014. Inhibitory effects of subcutaneous tumors in nude mice mediated by low-frequency ultrasound and microbubbles. Oncol Lett, 7(5): 1385–1390. https://doi.org/10.3892/ol.2014.1934
Shen ZY, Liu C, Wu MF, et al., 2017. Spiral computed tomography evaluation of rabbit VX2 hepatic tumors treated with 20 kHz ultrasound and microbubbles. Oncol Lett, 14(3):3124–3130. https://doi.org/10.3892/ol.2017.6557
Shen ZY, Jiang YM, Zhou YF, et al., 2018. High-speed photographic observation of the sonication of a rabbit carotid artery filled with microbubbles by 20-kHz low frequency ultrasound. Ultrason Sonochem, 40:980–987. https://doi.org/10.1016/j.ultsonch.2017.09.015
Shi MM, Chen L, Wang YX, et al., 2018. Effect of low-frequency pulsed ultrasound on drug delivery, antibacterial efficacy, and bone cement degradation in vancomycin-loaded calcium phosphate cement. Med Sci Monit, 24: 797–802. https://doi.org/10.12659/MSM.908776
Shimizu S, Yoshida T, Tsujioka M, et al., 2014. Autophagic cell death and cancer. Int J Mol Sci, 15(2):3145–3153. https://doi.org/10.3390/ijms15023145
Shriki J, 2014. Ultrasound physics. Crit Care Clin, 30(1):1–24. https://doi.org/10.1016/j.ccc.2013.08.004
Tang H, Mitragotri S, Blankschtein D, et al., 2001. Theoretical description of transdermal transport of hydrophilic permeants: application to low-frequency sonophoresis. J Pharm Sci, 90(5):545–568. https://doi.org/10.1002/1520-6017(200105)90:5<545::AID-JPS1012>3.0.CO;2-H
Tezel A, Sens A, Mitragotri S, 2002. Investigations of the role of cavitation in low-frequency sonophoresis using acoustic spectroscopy. J Pharm Sci, 91(2):444–453. https://doi.org/10.1002/jps.10024
Ueda H, Mutoh M, Seki T, et al., 2009. Acoustic cavitation as an enhancing mechanism of low-frequency sonophoresis for transdermal drug delivery. Biol Pharm Bull, 32(5): 916–920. https://doi.org/10.1248/bpb.32.916
Upadhyay A, Dalvi SV, 2019. Microbubble formulations: synthesis, stability, modeling and biomedical applications. Ultrasound Med Biol, 45(2):301–343. https://doi.org/10.1016/j.ultrasmedbio.2018.09.022
Wang P, Yin TH, Li JG, et al., 2016. Ultrasound-responsive microbubbles for sonography-guided siRNA delivery. Nanomedicine, 12(4):1139–1149. https://doi.org/10.1016/j.nano.2015.12.361
Wang Y, 2015. Researches in Vitro About Mechanism of Increased Chemotherapeutic Effect of Prostate Cancer Cells by Low-frequency and Low-power Ultrasound Combined with Microbubble. PhD Dissemination, Shanghai Jiao Tong University, Shanghai, China (in Chinese).
Wu BL, Qiao Q, Han X, et al., 2016. Targeted nanobubbles in low-frequency ultrasound-mediated gene transfection and growth inhibition of hepatocellular carcinoma cells. Tumour Biol, 37(9):12113–12121. https://doi.org/10.1007/s13277-016-5082-2
Wu JR, Nyborg WL, 2008. Ultrasound, cavitation bubbles and their interaction with cells. Adv Drug Deliv Rev, 60(10): 1103–1116. https://doi.org/10.1016/j.addr.2008.03.009
Wu YQ, Liu XB, Qin ZZ, et al., 2018. Low-frequency ultrasound enhances chemotherapy sensitivity and induces autophagy in PTX-resistant PC-3 cells via the endoplasmic reticulum stress-mediated PI3K/Akt/mTOR signaling pathway. Oncol Targets Ther, 11:5621–5630. https://doi.org/10.2147/OTT.S176744
Xiao NN, Liu JH, Liao LL, et al., 2018. Ultrasound combined with microbubbles increase the delivery of doxorubicin by reducing the interstitial fluid pressure. Ultrasound Quart, in press. https://doi.org/10.1097/RUQ.0000000000000381
Yang Y, Bai WK, Chen YN, et al., 2015a. Low-frequency and low-intensity ultrasound-mediated microvessel disruption enhance the effects of radiofrequency ablation on prostate cancer xenografts in nude mice. Mol Med Rep, 12(5): 7517–7525. https://doi.org/10.3892/mmr.2015.4375
Yang Y, Bai WK, Chen YN, et al., 2015b. Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design. Oncol Lett, 10(5):2999–3007. https://doi.org/10.3892/ol.2015.3716
Yang Y, Bai WK, Chen YN, et al., 2016. Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: a novel type of chemoembolization. Oncol Lett, 12(2):1011–1018. https://doi.org/10.3892/ol.2016.4703
Zarzynska JM, 2014. The importance of autophagy regulation in breast cancer development and treatment. Biomed Res Int, 2014:710345. https://doi.org/10.1155/2014/710345
Zhang L, Yin TH, Li B, et al., 2018. Size-modulable nano-probe for high-performance ultrasound imaging and drug delivery against cancer. ACS Nano, 12(4):3449–3460. https://doi.org/10.1021/acsnano.8b00076
Zhang W, Shou WD, Xu YJ, et al., 2017. Low-frequency ultrasound-induced VEGF suppression and synergy with dendritic cell-mediated anti-tumor immunity in murine prostate cancer cells in vitro. Sci Rep, 7:5778. https://doi.org/10.1038/s41598-017-06242-8
Zhao L, Feng Y, Shi AW, et al., 2015. Apoptosis induced by microbubble-assisted acoustic cavitation in k562 cells: the predominant role of the cyclosporin A-dependent mitochondrial permeability transition pore. Ultrasound Med Biol, 41(10):2755–2764. https://doi.org/10.1016/j.ultrasmedbio.2015.05.021
Zhao RR, Liang XL, Zhao B, et al., 2018. Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer. Biomaterials, 173:58–70. https://doi.org/10.1016/j.biomaterials.2018.04.054
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Project supported by the Health and Family Planning Commission of Zhejiang Province (No. 2017KY676), China
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Wang, Ly., Zheng, Ss. Advances in low-frequency ultrasound combined with microbubbles in targeted tumor therapy. J. Zhejiang Univ. Sci. B 20, 291–299 (2019). https://doi.org/10.1631/jzus.B1800508
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DOI: https://doi.org/10.1631/jzus.B1800508