Abstract
Chemically functionalized gas-filled bubbles with a versatile micro/nano-sized scale have witnessed a long history of developments and emerging applications in disease diagnosis and treatments. In combination with ultrasound and image-guidance, micro/nanobubbles have been endowed with the capabilities of biomedical imaging, drug delivery, gene transfection and disease-oriented therapy. As an external stimulus, ultrasound (US)-mediated targeting treatments have been achieving unprecedented efficiency. Nowadays, US is playing a crucial role in visualizing biological/pathological changes in lives as a reliable imaging technique and a powerful therapeutic tool. This review retrospects the history of ultrasound, the chemistry of functionalized agents and summarizes recent advancements of functional micro/nanobubbles as US contrast agents in preclinical and transclinical research. Latest ultrasound-based treatment modalities in association with functional micro/nanobubbles have been highlighted as their great potentials for disease precision therapy. It is believed that these state-of-the-art micro/nanobubbles will become a booster for ultrasound medicine and visualizable guidance to serve future human healthcare in a more comprehensive and practical manner.
Article PDF
Similar content being viewed by others
References
(a) American National Standard Institute. American national standard: accoustical terminology. New York: Acoustical Society of America.; (b)1994.
Oda F, Corso JF. J Acoust Soc Am, 1962, 34: 746
Liu HL, Fan CH, Ting CY, Yeh CK. Theranostics, 2014, 4: 432–444
Unger E, Porter T, Lindner J, Grayburn P. Adv Drug Deliver Rev, 2014, 72: 110–126
Sun RR, Noble ML, Sun SS, Song S, Miao CH. J Control Release, 2014, 182: 111–120
Wang X, Niu D, Li P, Wu Q, Bo X, Liu B, Bao S, Su T, Xu H, Wang Q. ACS Nano, 2015, 9: 5646–5656
Leon A, Perera R, Nittayacharn P, Cooley M, Jung O, Exner AA. Adv Cancer Res, 2018, 139: 57–84
Gramiak R, Shah PM. Invest Rad, 1968, 3: 356–366
Kremkau FW, Gramiak R, Carstensen EL, Shah PM, Kramer DH. Am J Roentgenology, 1970, 110: 177–183
Feinstein SB, Cheirif J, Ten Cate FJ, Silverman PR, Heidenreich PA, Dick C, Desir RM, Armstrong WF, Quinones MA, Shah PM. J Am College Cardiology, 1990, 16: 316–324
Appis AW, Tracy MJ, Feinstein SB. Echo Res Practice, 2015, 2: R55–R62
Keller MW, Glasheen W, Kaul S. J Am Soc Echocard, 1989, 2: 48–52
Podell S, Burrascano C, Gaal M, Golec B, Maniquis J, Mehlhaff P. Biotechnol Appl Biochem, 1999, 30: 213–223
Goertz DE, de Jong N, van der Steen AFW. Ultrasound Med Biol, 2007, 33: 1376–1388
Schneider M. Eur Radiol, 1999, 9: S347–S348
Sontum PC. Ultrasound Med Biol, 2008, 34: 824–833
Bhutani MS, Hoffman BJ, van Velse A, Hawes RH. Endoscopy, 1997, 29: 635–639
Christiansen C, Kryvi H, Sontum PC, Skotland T. Biotechnol Appl Biochem, 1994, 19: 307–320
Keller MW, Feinstein SB, Watson DD. Am Heart J, 1987, 114: 570–575
Cohen JL, Cheirif J, Segar DS, Gillam LD, Gottdiener JS, Hausnerova E, Bruns DE. J Am College Cardiology, 1998, 32: 746–752
Cavalieri F, Ashokkumar M, Grieser F, Caruso F. Langmuir, 2008, 24: 10078–10083
Wang S, Hossack JA, Klibanov AL. J Drug Targeting, 2018, 26: 420–434
Wheatley M. Biomaterials, 1990, 11: 713–717
Narayan P, Wheatley MA. Polym Eng Sci, 1999, 39: 2242–2255
Liu W, Wen S, Jiang L, An X, Zhang M, Wang H, Zhang Z, Zhang G, Shi X. CNANO, 2014, 10: 543–552
Lukianova-Hleb EY, Ren X, Zasadzinski JA, Wu X, Lapotko DO. Adv Mater, 2012, 24: 3831–3837
Shen Y, Lv W, Yang H, Cai W, Zhao P, Zhang L, Zhang J, Yuan L, Duan Y. Cancer Lett, 2019, 455: 14–25
Bauer A, Blomley M, Leen E, Cosgrove D, Schlief R. Eur Radiol, 1999, 9: S349–S352
Forsberg F, Goldberg BB, Liu JB, Merton DA, Rawool NM, Shi WT. Radiology, 1999, 210: 125–132
Fokong S, Siepmann M, Liu Z, Schmitz G, Kiessling F, Gätjens J. Ultrasound Med Biol, 2011, 37: 1622–1634
Koczera P, Wu Z, Fokong S, Theek B, Appold L, Jorge S, Möckel D, Liu Z, Curaj A, Storm G, van Zandvoort M, Kiessling F, Lammers T. Drug Deliv Transl Res, 2012, 2: 56–64
Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F, Gätjens J. Biomaterials, 2011, 32: 6155–6163
Cavalieri F, El Hamassi A, Chiessi E, Paradossi G. Langmuir, 2005, 21: 8758–8764
Brismar TB, Grishenkov D, Gustafsson B, Härmark J, Barrefelt Å, Kothapalli SVVN, Margheritelli S, Oddo L, Caidahl K, Hebert H, Paradossi G. Biomacromolecules, 2012, 13: 1390–1399
Böhmer MR, Schroeders R, Steenbakkers JAM, de Winter SHPM, Duineveld PA, Lub J, Nijssen WPM, Pikkemaat JA, Stapert HR. Colloids Surfs A-Physicochem Eng Aspects, 2006, 289: 96–104
Unger EC, Porter T, Culp W, Labell R, Matsunaga T, Zutshi R. Adv Drug Deliver Rev, 2004, 56: 1291–1314
Sanchez K, Barr RG. Ultrasound Q, 2009, 25: 171–173
Jiang N, Xie B, Zhang X, He M, Li K, Bai J, Wang Z, He J, Zhang L. Cardiovasc Intervent Radiol, 2014, 37: 1321–1328
Singhal S, Moser CC, Wheatley MA. Langmuir, 1993, 9: 2426–2429
Sirlin CB, Girard MS, Steinbach GC, Baker KG, Broderdorf SK, Hall LA, Mattrey RF. Int J Imag Syst Technol, 2015, 8: 82–88
Pelura TJ. Academic Rad, 1998, 5: S69–S71
Ota T, Ono S. BJR, 2004, 77: 148–149
Wu Y, Peng H, Zhao X. Ultrasound Med Biol, 2015, 41: 967–974
Oeffinger BE, Wheatley MA. Ultrasonics, 2004, 42: 343–347
Xu JS, Huang J, Qin R, Hinkle GH, Povoski SP, Martin EW, Xu RX. Biomaterials, 2010, 31: 1716–1722
Son S, Min HS, You DG, Kim BS, Kwon IC. Nano Today, 2014, 9: 525–540
Xing Z, Wang J, Ke H, Zhao B, Yue X, Dai Z, Liu J. Nanotechnology, 2010, 21: 145607
Zheng R, Yin T, Wang P, Zheng R, Zheng B, Cheng D, Zhang X, Shuai XT. IJN, 2012, 895
Liberman A, Martinez HP, Ta CN, Barback CV, Mattrey RF, Kono Y, Blair SL, Trogler WC, Kummel AC, Wu Z. Biomaterials, 2012, 33: 5124–5129
Hundley WG, Kizilbash AM, Afridi I, Franco F, Peshock RM, Grayburn PA. J Am College Cardiology, 1998, 32: 1426–1432
Rainbird AJ, Mulvagh SL, Oh JK, McCully RB, Klarich KW, Shub C, Mahoney DW, Pellikka PA. J Am Soc Echocard, 2001, 14: 378–385
Darge K, Zieger B, Rohrschneider W, Ghods S, Wunsch R, Troeger J. Am J Roentgenology, 2012, 177: 1411–1415
Ferrante EA, Pickard JE, Rychak J, Klibanov A, Ley K. J Control Release, 2009, 140: 100–107
Quillard T, Libby P. Circ Res, 2012, 111: 231–244
Schreglmann SR, Bauer R, Hägele-Link S, Bhatia KP, Natchev P, Wegener N, Lebeda A, Werner B, Martin E, Kägi G. Neurology, 2017, 88: 1329–1333
Jolesz FA. Annu Rev Med, 2009, 60: 417–430
Lammers T, Koczera P, Fokong S, Gremse F, Ehling J, Vogt M, Pich A, Storm G, van Zandvoort M, Kiessling F. Adv Funct Mater, 2015, 25: 36–43
Xiao YD, Paudel R, Liu J, Ma C, Zhang ZS, Zhou SK. Int J Mol Med, 2016, 38: 1319–1326
Feshitan JA, Vlachos F, Sirsi SR, Konofagou EE, Borden MA. Biomaterials, 2012, 33: 247–255
Feshitan JA, Boss MA, Borden MA. Langmuir, 2012, 28: 15336–15343
Liu Z, Koczera P, Doleschel D, Kiessling F, Gätjens J. Chem Commun, 2012, 48: 5142–5144
Liu Z, Shi C, Li Y, Song Y, Xu Q. RSC Adv, 2016, 6: 32710–32714
Chen M, Liang X, Gao C, Zhao R, Zhang N, Wang S, Chen W, Zhao B, Wang J, Dai Z. ACS Nano, 2018, 12: 7312–7326
Pellow C, O’Reilly MA, Hynynen K, Zheng G, Goertz DE. Nano Lett, 2020, 20: 4512–4519
Zackrisson S, van de Ven SMWY, Gambhir SS. Cancer Res, 2014, 74: 979–1004
Ishihara. J Anal Oncol, 2013, 2: 81
Meng Z, Zhou X, She J, Zhang Y, Feng L, Liu Z. Nano Lett, 2019, 19: 8109–8117
Ferrara KW, Borden MA, Zhang H. Acc Chem Res, 2009, 42: 881–892
Tartis MS, Kruse DE, Zheng H, Zhang H, Kheirolomoom A, Marik J, Ferrara KW. J Control Release, 2008, 131: 160–166
Ahmed M, Gustafsson B, Aldi S, Dusart P, Egri G, Butler LM, Bone D, Dähne L, Hedin U, Caidahl K. Cel Mol Bioeng, 2019, 12: 15–32
Subramaniam R, Omar S, Madenan N, Abdullah B. Ultrasound Obst Gyn, 2013, 10: 11–17
Ringold S. J Am Med Ass, 2004, 292: 2826
Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany C, Hynnen K, Macdanold N, Inbar Y, Itzchak Y, Rabinovici J, Kim K, Geschwind JF, Hesley G, Gostout B, Ehrenstein T, Hengst S, Sklair-Levy M, Shushan A, Jolesz F. Am J Roentgenology, 2012, 183: 1713–1719
Arif WM, Elsinga PH, Gasca-Salas C, Versluis M, Martínez-Fernández R, Dierckx RAJO, Borra RJH, Luurtsema G. J Control Release, 2020, 324: 303–316
Santos MA, Wu SK, Li Z, Goertz DE, Hynynen K. Int J Hyperthermia, 2018, 35: 599–611
Zhao R, Liang X, Zhao B, Chen M, Liu R, Sun S, Yue X, Wang S. Biomaterials, 2018, 173: 58–70
Li WP, Su CH, Chang YC, Lin YJ, Yeh CS. ACS Nano, 2016, 10: 2017–2027
Meng L, Liu X, Wang Y, Zhang W, Zhou W, Cai F, Li F, Wu J, Xu L, Niu L, Zheng H. Adv Sci, 2019, 6: 1900557
Lentacker I, De Cock I, Deckers R, De Smedt SC, Moonen CTW. Adv Drug Deliver Rev, 2014, 72: 49–64
van den Bijgaart RJE, Eikelenboom DC, Hoogenboom M, Fütterer JJ, den Brok MH, Adema GJ. Cancer Immunol Immunother, 2017, 66: 247–258
Uchida T, Nakano M, Hongo S, Shoji S, Nagata Y, Satoh T, Baba S, Usui Y, Terachi T. Int J Urology, 2012, 19: 187–201
Lee HM, Hong JH, Choi HY. Prostate Cancer Prostatic Dis, 2006, 9: 439–443
Feng G, Hao L, Xu C, Ran H, Zheng Y, Li P, Cao Y, Wang Q, Xia J, Wang Z. IJN, 2017, Volume 12: 4647–4659
Cullion K, Petishnok LC, Sun T, Santamaria CM, Pemberton GL, McDannold NJ, Kohane DS. Drug Deliv Transl Res, 2020, 10: 1507–1516
Cheng C, Xiao Z, Huang G, Zhang L, Bai J. BJOG-Int J Obstet Gy, 2017, 124: 78–86
Liu Z, Kiessling F, Gätjens J. J Nanomaterials, 2010, 2010: 894303
Hijnen N, Langereis S, Grüll H. Adv Drug Deliver Rev, 2014, 72: 65–81
Anthony GJ, Bader KB, Wang J, Zamora M, Ostdiek A, Antic T, Krueger S, Weiss S, Trogler WC, Blair SL, Kummel AC, Sammet S. Med Phys, 2019, 46: 774–788
Niu D, Wang X, Li Y, Zheng Y, Li F, Chen H, Gu J, Zhao W, Shi J. Adv Mater, 2013, 25: 2686–2692
Chung DJ, Cho SH, Lee JM, Hahn ST. Eur J Rad, 2012, 81: e519–e523
Tachibana K, Tachibana S. Circulation, 1995, 92: 1148–1150
Xie F, Tsutsui JM, Lof J, Unger EC, Johanning J, Culp WC, Matsunaga T, Porter TR. Ultrasound Med Biol, 2005, 31: 979–985
Molina CA, Ribo M, Rubiera M, Montaner J, Santamarina E, Delgado-Mederos R, Arenillas JF, Huertas R, Purroy F, Delgado P, Alvarez-Sabin J. Stroke, 2006, 37: 425–429
Molina CA, Barreto AD, Tsivgoulis G, Sierzenski P, Malkoff MD, Rubiera M, Gonzales N, Mikulik R, Pate G, Ostrem J, Singleton W, Manvelian G, Unger EC, Grotta JC, Schellinger PD, Alexandrov AV. Ann Neurol, 2009, 66: 28–38
Petit B, Yan F, Bussat P, Bohren Y, Gaud E, Fontana P, Tranquart F, Allémann E. J Drug Deliver Sci Tech, 2015, 25: 29–35
Wood AKW, Sehgal CM. Ultrasound Med Biol, 2015, 41: 905–928
Gao Z, Zheng J, Yang B, Wang Z, Fan H, Lv Y, Li H, Jia L, Cao W. Cancer Lett, 2013, 335: 93–99
Saha S, Bhanja P, Partanen A, Zhang W, Liu L, Tomé WA, Guha C. Oncoscience, 2014, 1: 434–445
Liu Y, Miyoshi H, Nakamura M. J Control Release, 2006, 114: 89–99
Sontum P, Kvåle S, Healey AJ, Skurtveit R, Watanabe R, Matsumura M, Østensen J. Int J Pharm, 2015, 495: 1019–1027
Park K. J Control Release, 2016, 236: 117
van Wamel A, Sontum PC, Healey A, Kvåle S, Bush N, Bamber J, de Lange Davies C. J Control Release, 2016, 236: 15–21
Fan Z, Kumon RE, Deng CX. Therapeutic Deliver, 2014, 5: 467–486
Fan Z, Chen D, Deng CX. J Control Release, 2013, 170: 401–413
Unger EC, Matsunaga TO, McCreery T, Schumann P, Sweitzer R, Quigley R. Eur J Rad, 2001, 42: 160–168
Ibsen S, Schutt S, Esener S. DDDT, 2013, 7: 375–388
Leong-Poi H, Kuliszewski MA, Lekas M, Sibbald M, Teichert-Kuliszewska K, Klibanov AL, Stewart DJ, Lindner JR. Circ Res, 2007, 101: 295–303
Dewitte H, Van Lint S, Heirman C, Thielemans K, De Smedt SC, Breckpot K, Lentacker I. J Control Release, 2014, 194: 28–36
Li T, Zhou J, Zhang C, Zhi X, Niu J, Fu H, Song J, Cui D. NPG Asia Mater, 2018, 10: 1046–1060
Lindsey BD, Kim J, Dayton PA, Jiang X. IEEE Trans Ultrason Ferroelect Freq Contr, 2017, 64: 1078–1086
Rajendram R, Hussain A, Mahmood N, Kharal M. Ultrasound J, 2020, 12: 49
Jung EM, Stroszczynski C, Jung F. CH, 2020, 75: 19–26
Tsutsui JM, Xie F, Cano M, Chomas J, Phillips P, Radio SJ, Lof J, Porter TR. J Am College Cardiology, 2004, 44: 1036–1046
Porter TR, Mulvagh SL, Abdelmoneim SS, Becher H, Belcik JT, Bierig M, Choy J, Gaibazzi N, Gillam LD, Janardhanan R, Kutty S, Leong-Poi H, Lindner JR, Main ML, Mathias Jr. W, Park MM, Senior R, Villanueva F. J Am Soc Echocard, 2018, 31: 241–274
Acknowledgements
This research was financially supported by the National Natural Science Foundation of China (21575106, 82072057).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Zhang, C., Li, Y., Ma, X. et al. Functional micro/nanobubbles for ultrasound medicine and visualizable guidance. Sci. China Chem. 64, 899–914 (2021). https://doi.org/10.1007/s11426-020-9945-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-020-9945-4