Nanobubbles: A Promising Efficient Tool for Therapeutic Delivery

References

• Qin S Caskey CF Ferrara KW . Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering. Phys. Med. Biol.54 (6), R27–R57 (2009).
   PubMed Web of Science ®Google Scholar
• Lentacker I De Smedt SC Sanders NN . Drug loaded microbubble design for ultrasound triggered delivery. Soft Matter5 (11), 2161–2170 (2009).
   Web of Science ®Google Scholar
• Fan Z Kumon RE Deng CX . Mechanisms of microbubble-facilitated sonoporation for drug and gene delivery. Ther. Deliv.5 (4), 467–486 (2014).
   PubMedGoogle Scholar
• Lentacker I De Cock I Deckers R et al. Understanding ultrasound induced sonoporation: definitions and underlying mechanisms. Adv. Drug Deliv. Rev.72, 49–64 (2014).
   PubMed Web of Science ®Google Scholar
• Yu H Lin Z Xu L et al. Theoretical study of microbubble dynamics in sonoporation. Ultrasonics61, 136–144 (2015).
   PubMed Web of Science ®Google Scholar
• Sirsi SR Borden MA . State-of-the-art materials for ultrasound-triggered drug delivery. Adv. Drug Deliv. Rev.72, 3–14 (2014).
   PubMed Web of Science ®Google Scholar
• Paefgen V Doleschel D Kiessling F . Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery. Front. Pharmacol.6, 197 (2015).
   PubMed Web of Science ®Google Scholar
• Klibanov AL . Ultrasound contrast agents: development of the field and current status. Top. Curr. Chem.222, 73–106 (2002).
   Web of Science ®Google Scholar
• Marxer EEJ Brüßler J Becker A et al. Development and characterization of new nanoscaled ultrasound active lipid dispersions as contrast agents. Eur. J. Pharm. Biopharm.77, 430–437 (2011).
   PubMed Web of Science ®Google Scholar
• O'Neill BE Rapoport N . Phase-shift, stimuli-responsive drug carriers for targeted delivery. Ther. Deliv.2 (9), 1165–87 (2011).
   PubMedGoogle Scholar
• Cavalli R Bisazza A Lembo D . Micro-and nanobubbles: a versatile non-viral platform for gene delivery. Int. J. Pharm.456 (2), 437–445 (2013).
   PubMed Web of Science ®Google Scholar
• Fang J Nakamura H Maeda H . The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv. Drug Del. Rev.63 (3), 136–151 (2011).
   PubMed Web of Science ®Google Scholar
• Fokong S Theek B Wu Z et al. Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles. J. Control. Rel.163, 75–81 (2012).
   PubMed Web of Science ®Google Scholar
• Zhang C Cao H Li Q et al. Enhancement effect of ultrasound-induced microbubble cavitation on branched polyethylenimine-mediated VEGF165 transfection with varied N/P ratio. Ultrasound Med. Biol.39, 161–171 (2013).
   PubMed Web of Science ®Google Scholar
• Pitt WG Husseini GA . Ultrasound in drug and gene delivery. Adv. Drug Deliv. Rev.60, 1095–1096 (2008).
   PubMed Web of Science ®Google Scholar
• Kim C Qin R Xu JS et al. Multifunctional microbubbles and nanobubbles for photoacoustic and ultrasound imaging. J. Biom. Optics15 (1), 010510–010510 (2010).
   PubMed Web of Science ®Google Scholar
• Rapoport N . Phase‐shift, stimuli‐responsive perfluorocarbon nanodroplets for drug delivery to cancer. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.4 (5), 492–510 (2012).
   PubMed Web of Science ®Google Scholar
• Rapoport NY Efros AL Christensen DA et al. Microbubble generation in phase-shift nanoemulsions used as anticancer drug carriers. Bubble Sci. Eng. Technol.1 (1–2), 31–39 (2009).
   PubMedGoogle Scholar
• Van Liew HD Raychaudhuri S . Stabilized bubbles in the body: pressure-radius relationships and the limits to stabilization. J. Appl. Physiol.82 (6), 2045–2053 (1997).
   PubMed Web of Science ®Google Scholar
• Kooiman K Vos HJ Versluis M et al. Acoustic behavior of microbubbles and implications for drug delivery. Adv. Drug Deliv. Rev.72, 28–48 (2014).
   PubMed Web of Science ®Google Scholar
• Kwan JJ Borden MA . Lipid monolayer collapse and microbubble stability. Adv. Colloids Interface Sci.183, 82–99 (2012).
   PubMed Web of Science ®Google Scholar
• Zhang Lu Luo Lan Zhao Sui et al. The synergistic effect of mixed surfactants in reducing interfacial tension between binary aqueous surfactant solutions and normal alkanes of different carbon number. Oilfield Chemistry3, 022 (2000).
   Google Scholar
• Tsukahara S Mukai K Watanabe S et al. In situ fluorescence microscopic measurements of the phase transition behavior of dipalmitoyl phosphatidylcholine monolayers prepared at hydrocarbon/water interfaces. Solvent Extr. Res. Dev.18 (0), 149–158 (2011).
   Google Scholar
• Dressaire E Bee R Bell DC et al. Interfacial polygonal nanopatterning of stable microbubbles. Science320 (5880), 1198–1201 (2008).
   PubMed Web of Science ®Google Scholar
• Krupka TM Solorio L Wilson RE et al. Formulation and characterization of echogenic lipid−pluronic nanobubbles. Mol. Pharm.7 (1), 49–59 (2009).
   Google Scholar
• Cruz A Vázquez L Vélez M et al. Influence of a fluorescent probe on the nanostructure of phospholipid membranes: dipalmitoylphosphatidylcholine interfacial monolayers. Langmuir21 (12), 5349–5355 (2005).
   PubMed Web of Science ®Google Scholar
• Moghaddam B Ali MH Wilkhu J et al. The application of monolayer studies in the understanding of liposomal formulations. Int. J. Pharm.417 (1), 235–244 (2011).
   PubMedGoogle Scholar
• Eeman M Berquand A Dufrene YF et al. Penetration of surfactin into phospholipid monolayers: nanoscale interfacial organization. Langmuir22 (26), 11337–11345 (2006).
   PubMed Web of Science ®Google Scholar
• Krafft MP Fainerman VB Miller R . Modeling of the effect of fluorocarbon gases on the properties of phospholipid monolayers and the adsorption dynamics of their aqueous solutions or dispersions. Colloid. Polym. Sci.293 (11), 3091–3097 (2015).
   Web of Science ®Google Scholar
• Wu H Rognin NG Krupka TM et al. Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents. Ultrasound. Med. Biol.39 (11), 2137–2146 (2013).
   PubMed Web of Science ®Google Scholar
• Krafft MP . Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research. Adv. Drug Del. Rev.47 (2), 209–228 (2001).
   PubMed Web of Science ®Google Scholar
• Sheeran PS Dayton PA . Phase-change contrast agents for imaging and therapy. Curr. Pharm. Des.18 (15), 2152–2165 (2012).
   PubMed Web of Science ®Google Scholar
• Kandadai MA Mohan P Lin G et al. Comparison of surfactants used to prepare aqueous perfluoropentane emulsions for pharmaceutical applications. Langmuir26 (7), 4655–4660 (2010).
   PubMed Web of Science ®Google Scholar
• Kripfgans OD Fowlkes JB Miller DL et al. Acoustic droplet vaporization for therapeutic and diagnostic applications. Ultrasound Med. Biol.26 (7), 1177–1189 (2000).
   PubMed Web of Science ®Google Scholar
• Wong ZZ Kripfgans OD Qamar A et al. Bubble evolution in acoustic droplet vaporization at physiological temperature via ultra-high speed imaging. Soft Matter7 (8), 4009–4016 (2011).
   Web of Science ®Google Scholar
• Lin CY Pitt WG . Acoustic droplet vaporization in biology and medicine. BioMed Res. Int.2013, 1–13 (2013).
   Web of Science ®Google Scholar
• Rapoport N Nam KH Gupta R et al. Ultrasound-mediated tumor imaging and nanotherapy using drug loaded block copolymer stabilized perfluorocarbon nanoemulsions. J. Control. Rel.153, 4–15 (2011).
   PubMed Web of Science ®Google Scholar
• Kawabata K Sugita N Yoshikawa H et al. Nanoparticles with multiple perfluorocarbons for controllable ultrasonically induced phase shifting. Jpn. J. Appl. Phys.44, 5 (2005).
   Web of Science ®Google Scholar
• Phillips LC Puett C Sheeran PS et al. Phase-shift perfluorocarbon agents enhance high intensity focused ultrasound thermal delivery with reduced near-field heating. J. Acoust. Soc. Am.134, 1473–1482 (2013).
   PubMed Web of Science ®Google Scholar
• Mountford PA Sirsi SR Borden MA . Condensation phase diagrams for lipid-coated perfluorobutane microbubbles. Langmuir30 (21), 6209–6218 (2014).
   PubMed Web of Science ®Google Scholar
• Mountford PA Thomas AN Borden MA . Thermal activation of superheated lipid-coated perfluorocarbon drops. Langmuir31 (16), 4627–4634 (2015).
   PubMed Web of Science ®Google Scholar
• Kooiman K Böhmer MR Emmer M et al. Oil-filled polymer microcapsules for ultrasound-mediated delivery of lipophilic drugs. J. Control. Rel.133 (2), 109–118 (2009).
   PubMed Web of Science ®Google Scholar
• Marmottant P Bouakaz A de Jong N et al. Buckling resistance of solid shell bubbles under ultrasound. J. Acoust. Soc. Am.129 (3), 1231–1239 (2011).
   PubMed Web of Science ®Google Scholar
• Glynos E Koutsos V McDicken WN et al. Nanomechanics of biocompatible hollow thin-shell polymer microspheres. Langmuir25 (13), 7514–7522 (2009).
   PubMed Web of Science ®Google Scholar
• Sarkar K Shi WT Chatterjee D et al. Characterization of ultrasound contrast microbubbles using in vitro experiments and viscous and viscoelastic interface models for encapsulation. J. Acoust. Soc. Am.118, 539–550 (2005).
   PubMed Web of Science ®Google Scholar
• Church CC . The effects of an elastic solid surface layer on the radial pulsations of gas bubbles. J. Acoust. Soc. Am.97, 1510–1521 (1995).
   Web of Science ®Google Scholar
• Marmottant P van der Meer S Emmer M et al. A model for large amplitude oscillations of coated bubbles accounting for buckling and rupture. J. Acoust. Soc. Am.118, 3499–3505 (2005).
   Web of Science ®Google Scholar
• Pu G Borden MA Longo ML . Collapse and shedding transitions in binary lipid monolayers coating microbubbles. Langmuir22, 2993–2999 (2006).
   PubMed Web of Science ®Google Scholar
• Rovers TA Sala G Van der Linden E Meinders MB . Temperature is key to yield and stability of BSA stabilized microbubbles. Food Hydrocolloids52, 106–115 (2016).
   Web of Science ®Google Scholar
• Talu E Lozano MM Powell RL et al. Long-term stability by lipid coating monodisperse microbubbles formed by a flow-focusing device. Langmuir22 (23), 9487–9490 (2006).
   PubMed Web of Science ®Google Scholar
• Riess JG . Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artif. Cells Blood Substit. Biotechnol.33 (1), 47–63 (2005).
   PubMed Web of Science ®Google Scholar
• Du Toit LC Govender T Pillay V et al. Investigating the effect of polymeric approaches on circulation time and physical properties of nanobubbles. Pharm. Res.28, 494–504 (2011).
   PubMed Web of Science ®Google Scholar
• Xie X Lin W Liu H et al. Ultrasound-responsive nanobubbles contained with peptide–camptothecin conjugates for targeted drug delivery. Drug Deliv.1–9 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Watanabe Y Horie S Funaki Y et al. Delivery of Na/I symporter gene into skeletal muscle using nanobubbles and ultrasound: visualization of gene expression by PET. J. Nuclear Med.51 (6), 951–958 (2010).
   PubMed Web of Science ®Google Scholar
• Bisazza A Civra A Donalisio M Lembo D Cavalli R . The in vitro characterization of dextran-based nanobubbles as possible DNA transfection agents. Soft Matter7 (22), 10590–10593 (2011).
   Web of Science ®Google Scholar
• Bisazza A Giustetto P Rolfo A et al. Microbubble-mediated oxygen delivery to hypoxic tissues as a new therapeutic device. Conf. Proc. IEEE Eng. Med. Biol. Soc.2008, 2067–2070 (2008).
   Google Scholar
• Cavalli R Bisazza A Giustetto P et al. Preparation and characterization of dextran nanobubbles for oxygen delivery. Int. J. Pharm.381 (2), 160–165 (2009).
   PubMedGoogle Scholar
• Matsuki N Ishikawa T Ichiba S Shiba N Ujike Y Yamaguchi T . Oxygen supersaturated fluid using fine micro/nanobubbles. Int. J. Nanomedicine9, 4495–4505 (2014).
   PubMed Web of Science ®Google Scholar
• Magnetto C Prato M Khadjavi A et al. Ultrasound-activated decafluoropentane-cored and chitosan-shelled nanodroplets for oxygen delivery to hypoxic cutaneous tissues. RSC Adv.4 (72), 38433–38441 (2014).
   Web of Science ®Google Scholar
• Prato M Magnetto C Jose J et al. 2H, 3H-decafluoropentane-based nanodroplets: new perspectives for oxygen delivery to hypoxic cutaneous tissues. PLoS ONE10 (3), e0119769 (2015).
   PubMed Web of Science ®Google Scholar
• Basilico N Magnetto C D'Alessandro S et al. Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium. Toxicol. Appl. Pharmacol.288 (3), 330–338 (2015).
   PubMed Web of Science ®Google Scholar
• Hwang TL Lin YK Chi CH Huang TH Fang JY . Development and evaluation of perfluorocarbon nanobubbles for apomorphine delivery. J. Pharm. Sci.98 (10), 3735–3747 (2009).
   PubMed Web of Science ®Google Scholar
• Banche G Prato M Magnetto C et al. Antimicrobial chitosan nanodroplets: new insights for ultrasound-mediated adjuvant treatment of skin infection. Future Microbiol.10 (6), 929–939 (2015).
   PubMed Web of Science ®Google Scholar
• Feshitan JA Vlachos F Sirsi SR Konofagou EE Borden MA . Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery. Biomaterials33 (1), 247–255 (2012).
   PubMed Web of Science ®Google Scholar
• Rapoport N Gao Z Kennedy A . Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy. J. Natl Cancer Inst.99, 1095–1106 (2007).
   PubMed Web of Science ®Google Scholar
• Rapoport NY Kennedy AM Shea JE Scaife CL Nam KH . Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/microbubbles. J. Control. Release138 (3), 268–276 (2009).
   PubMed Web of Science ®Google Scholar
• Eggen S Fagerland SM M⊘rch Ý et al. Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles. J. Control. Release187, 39–49 (2014).
   PubMed Web of Science ®Google Scholar
• Gao Z Kennedy AM Christensen DA Rapoport NY . Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy. Ultrasonic.48, 260–270 (2008).
   PubMed Web of Science ®Google Scholar
• Zhang X Zheng Y Wang Z et al. Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and Synergistic Targeted therapy of residual tumor during HIFU ablation. Biomaterials35 (19), 5148–5161 (2014).
   PubMed Web of Science ®Google Scholar
• Du L Jin Y Zhou W Zhao J . Ultrasound-triggered drug release and enhanced anticancer effect of doxorubicin-loaded poly(D,L-lactide-co-glycolide)-methoxy-poly(ethylene-glycol) nanodroplets. Ultrasound Med. Biol.37 (8), 1252–1258 (2011).
   PubMed Web of Science ®Google Scholar
• Deng L Li L Yang H et al. Development and optimization of doxorubicin loaded poly(lactic-co-glycolic acid) nanobubbles for drug delivery into HeLa cells. J. Nanosci. Nanotechnol.14 (4), 2947–2954 (2014).
   PubMed Web of Science ®Google Scholar
• Grishenkov D Kari L Brodin LA Brismar TB Paradossi G . In vitro contrast-enhanced ultrasound measurements of capillary microcirculation: comparison between polymer and phospholipid-shelled microbubbles. Ultrasonics51, 40–48 (2011).
   PubMed Web of Science ®Google Scholar
• Lentacker I De Geest BG Vandenbroucke RE et al. Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA. Langmuir22, 7273–7278 (2006).
   PubMed Web of Science ®Google Scholar
• Lee JY Carugo D Crake C et al. Nanoparticle-loaded protein-polymer nanodroplets for improved stability and conversion efficiency in ultrasound imaging and drug delivery. Adv. Mater.27 (37), 5484–5492 (2015).
   PubMed Web of Science ®Google Scholar
• Cavalieri F Ashokkumar M Grieser F et al. Ultrasonic synthesis of stable, functional lysozyme microbubbles. Langmuir24 (18), 10078–10083 (2008).
   PubMed Web of Science ®Google Scholar
• Korpanty G Grayburn P Shohet RV et al. Targeting vascular endothelium with avidin microbubbles. Ultrasound Med. Biol.31 (9), 1279–1283 (2005).
   PubMed Web of Science ®Google Scholar
• Kothapalli SV Oddo L Paradossi G Brodi LÅ Grishenkov D . Assessment of the viscoelastic and oscillation properties of a nano-engineered multimodality contrast agent. Ultrasound Med. Biol.40 (10), 2476–2487 (2014).
   PubMed Web of Science ®Google Scholar
• Tartis SM McCallan J Lum A et al. Therapeutic effects of paclitaxel-containing ultrasound contrast agents. Ultrasound Med. Biol.32, 1771–1780 (2006).
   PubMed Web of Science ®Google Scholar
• Xing Z Wang J Ke H et al. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging. Nanotechnology21 (14), 145607 (2010).
   PubMed Web of Science ®Google Scholar
• Hettiarachchi K Talu E Longo ML et al. On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging. Lab Chip7 (4), 463–468 (2007).
   PubMed Web of Science ®Google Scholar
• Delalande A Postema M Mignet N et al. Ultrasound and microbubble-assisted gene delivery: recent advances and ongoing challenges. Ther. Deliv.3 (10), 1199–1215 (2012).
   PubMedGoogle Scholar
• Borden MA Longo ML . Oxygen permeability of fully condensed lipid monolayers. J. Phys. Chem. B108, 6009–6016 (2004).
   Web of Science ®Google Scholar
• van Rooij T Luan Y Renaud G et al. Non-linear response and viscoelastic properties of lipid-coated microbubbles: DSPC versus DPPC. Ultrasound Med. Biol.41 (5), 1432–1445 (2015).
   PubMed Web of Science ®Google Scholar
• Xiong X Zhao F Shi M Yang H Liu Y . Polymeric microbubbles for ultrasonic molecular imaging and targeted therapeutics. J. Biomater. Sci, Polym. Ed.22 (4–6), 417–428 (2011).
   PubMed Web of Science ®Google Scholar
• Capece S Chessi E Cavalli R Giustetto P Grishenkov D Paradossi G . A general strategy for the obtainment of biodegradable polymer shelled microbubbles as theranostic device. Chem. Commun.49, 5763–5765 (2013).
   PubMed Web of Science ®Google Scholar
• Cavalli R Soster M Argenziano M Baroni S Giustetto P Terreno E . New crosslinked polymeric nanobubbles as in vitro and in vivo theranostic agent. Presented at : European Molecular Meeting 2014. Antwerp, Belgium, 4–6 June 2014.
   Google Scholar
• Stride E Edirisinghe M . Novel microbubble preparation technologies. Soft Matter4, 2350–2359 (2008).
   Web of Science ®Google Scholar
• Dhanaliwala AH Dixon AJ Lin D et al. In vivo imaging of microfluidic-produced microbubbles. Biomed. Microdevices17 (1), 23 (2015).
   PubMed Web of Science ®Google Scholar
• Wang S Dhanaliwala AH Chen JL et al. Production rate and diameter analysis of spherical monodisperse microbubbles from two-dimensional, expanding-nozzle flow-focusing microfluidic devices. Biomicrofluidics7 (1), 14103 (2013).
   PubMed Web of Science ®Google Scholar
• Sheeran PS Luois S Dayton PA Matsunaga TO . Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound. Langmuir ACS J. Surf. Colloids27, 10412–10420 (2011).
   PubMed Web of Science ®Google Scholar
• Cavalli R . Nanoscale bubbles: an alternative tool for anticancer drug delivery. Presented at : Leeds Microbubble Symposium. Leeds, England, 29–30 June 2015.
   Google Scholar
• Anderson KE Rogers JA Li D . An interfacial tension model of the interaction of water‐soluble polymers with phospholipid composite monolayers. J. Pharm. Pharmacol.49 (6), 587–591 (1997).
   PubMed Web of Science ®Google Scholar
• Santos HA García-Morales V Roozeman RJ Manzanares JA Kontturi K . Interfacial interaction between dextran sulfate and lipid monolayers: an electrochemical study. Langmuir21 (12), 5475–5484 (2005).
   PubMed Web of Science ®Google Scholar
• Van Eeten KMP Houben HHH Van der Shaaf J Schouten JC . An experimental and theoretical study of the size of bubbles formed between a rotating disc and a stationary wall. Chem. Eng. Sci.109, 251–263 (2014).
   Web of Science ®Google Scholar
• Vankova N Tcholakova S Denkov ND Ivanov IB Vulchev VD Danner T . Emulsification in turbulent flow. 1. Mean and maximum drop diameters in inertila and viscous regimes. J. Colloids Interface Science312, 363–380 (2007).
   PubMed Web of Science ®Google Scholar
• Geers B Dewitte H De Smedt SC Lentacker I . Crucial factors and emerging concepts in ultrasound-triggered drug delivery. J. Control. Release164 (3), 248–255 (2012).
   PubMed Web of Science ®Google Scholar
• Nomikou N Tiwari P Trehan T Gulati K McHale A . Studies on neutral, cationic and biotinylated cationic microbubbles in enhancing ultrasound-mediated gene delivery in-vitro and in-vivo. Acta Biomater.8, 1273–1280 (2012).
   PubMed Web of Science ®Google Scholar
• Cavalli R Bisazza A Giustetto P et al. Dextran multilayer microbubbles as ultrasound–triggered doxorubicin carriers. Presented at : iConference on Innovation Drug Delivery Aix-en-Provence. France, 3–6 October 2010.
   Google Scholar
• Nguyen AT Wrenn SP . Acoustically active liposome-nanobubble complexes for enhanced ultrasonic imaging and ultrasound-triggered drug delivery. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.6, 316–325 (2014).
   PubMed Web of Science ®Google Scholar
• Tinkov S Bekeredjian R Winter G Coester C . Microbubbles as ultrasound triggered drug carriers. J. Pharm. Sci.98 (6), 1935–1961 (2009).
   PubMed Web of Science ®Google Scholar
• Wang CH Huang YF Yeh CK . Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging. Langmuir27 (11), 6971–6976 (2011).
   PubMed Web of Science ®Google Scholar
• Ruttala HB Ko YT . Liposomal co-delivery of curcumin and albumin/paclitaxel nanoparticle for enhanced synergistic antitumor efficacy. Colloids Surf. B. Biointerfaces128, 419–426 (2015).
   PubMed Web of Science ®Google Scholar
• Jiang Q Hao S Xiao X et al. Production and characterization of a novel long-acting Herceptin-targeted nanobubble contrast agent specific for Her-2-positive breast cancers. Breast Cancer (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Yang H Cai W Xu L et al. NanobubbleAffibody: novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor. Biomaterials37, 279–288 (2015).
   PubMed Web of Science ®Google Scholar
• Fan X Wang L Guo Y et al. Ultrasonic nanobubbles carrying anti-PSMA nanobody: construction and application in prostate cancer-targeted imaging. PloS ONE10 (6), e0127419 (2015).
   PubMed Web of Science ®Google Scholar
• Suzuki M Koshiyama K Shinohara F et al. Nanobubbles enhanced drug susceptibility of cancer cells using ultrasound. International Congress Series1284, 338–339 (2005).
   Google Scholar
• Ji G Yang J Chen J . Preparation of novel curcumin-loaded multifunctional nanodroplets for combining ultrasonic development and targeted chemotherapy. Int. J. Pharm.466 (1), 314–320 (2014).
   PubMedGoogle Scholar
• Lin W Xie X Deng J et al. Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery. J. Drug Target1–13 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Rychak JJ Klibanov AL . Nucleic acid delivery with microbubbles and ultrasound. Adv. Drug Deliv. Rev.72, 82–93 (2014).
   PubMed Web of Science ®Google Scholar
• Suzuki R Oda Y Utoguchi N Maruyama K . Progress in the development of ultrasound-mediated gene delivery systems utilizing nano- and microbubbles. J. Control. Release149, 36–41 (2011).
   PubMed Web of Science ®Google Scholar
• Tlaxca J Anderson C Klibanov A et al. Analysis of in-vitro transfection by sonoporation using cationic and neutral microbubbles. Ultrasound Med. Biol.36, 1907–1918 (2010).
   PubMed Web of Science ®Google Scholar
• Suzuki R Takizawa T Negishi Y et al. Tumor specific ultrasound enhanced gene transfer in vivo with novel liposomal bubbles. J. Control. Release125, 137–144 (2008).
   PubMed Web of Science ®Google Scholar
• Endo-Takahashi Y Negishi Y Nakamura A et al. pDNA-loaded Bubble liposomes as potential ultrasound imaging and gene delivery agents. Biomaterials34 (11), 2807–2813 (2013).
   PubMed Web of Science ®Google Scholar
• Horie S Watanabe Y Ono M Mori S Kodama T . Evaluation of antitumor effects following tumor necrosis factor-α gene delivery using nanobubbles and ultrasound. Cancer Sci.102, 2082–2089 (2011).
   PubMed Web of Science ®Google Scholar
• Cavalli R Bisazza A Trotta F et al. New chitosan nanobubbles for ultrasound-mediated gene delivery: preparation and in vitro characterization. Int. J. Nanomed.7, 3309–3318 (2012).
   PubMed Web of Science ®Google Scholar
• Yin T Wang P Li J et al. Ultrasound-sensitive siRNA-loaded nanobubbles formed by hetero-assembly of polymeric micelles and liposomes and their therapeutic effect in gliomas. Biomaterials34 (18), 4532–4543 (2013).
   PubMed Web of Science ®Google Scholar
• Yin T Wang P Li J et al. Tumor-penetrating codelivery of siRNA and paclitaxel with ultrasound-responsive nanobubbles hetero-assembled from polymeric micelles and liposomes. Biomaterials35 (22), 5932–5943 (2014).
   PubMed Web of Science ®Google Scholar
• Wang L Zhang M Tan K et al. Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. PloS ONE9 (5), e96586 (2014).
   PubMed Web of Science ®Google Scholar
• Xie X Yang Y Lin W et al. Cell-penetrating peptide-siRNA conjugate loaded YSA-modified nanobubbles for ultrasound triggered siRNA delivery. Colloids Surf. B.136, 641–650 (2015).
   PubMed Web of Science ®Google Scholar
• Zhou ZY Zhang P Ren JL et al. Synergistic effects of ultrasound-targeted microbubble destruction and TAT peptide on gene transfection: an experimental study in vitro and in vivo. J. Control. Release170, 437–444 (2013).
   PubMed Web of Science ®Google Scholar
• Zhu F Jiang Y Luo F et al. Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model. J. Drug Target23 (4), 323–334 (2015).
   PubMed Web of Science ®Google Scholar
• Stride E . Physical principles of microbubbles for ultrasound imaging and therapy. Front. Neurol. Neurosci.36, 11–22 (2015).
   PubMedGoogle Scholar
• Mahalingam S Raimi-Abraham BT Craig DQ et al. Formation of protein and protein–gold nanoparticle stabilized microbubbles by pressurized gyration. Langmuir31, 659–666 (2015).
   PubMed Web of Science ®Google Scholar
• Parhizkar M Stride E Edirisinghe M . Preparation of monodisperse microbubbles using an integrated embedded capillary T-junction with electrohydrodynamic focusing. Lab Chip14, 2437–2446 (2014).
   PubMed Web of Science ®Google Scholar
• Fix SM Borden MA Dayton PA . Therapeutic gas delivery via microbubbles and liposomes. J. Control. Release209, 139–149 (2015).
   PubMed Web of Science ®Google Scholar
• Kheir JN Polizzotti BD Thomson LM et al. Bulk manufacture of concentrated oxygen gas‐filled microparticles for intravenous oxygen delivery. Adv. Healthcare Mater.2 (8), 1131–1141 (2013).
   Web of Science ®Google Scholar
• Thomson LM Polizzotti BD McGowan FX Kheir JN . Manufacture of concentrated, lipid-based oxygen microbubble emulsions by high shear homogenization and serial concentration. J. Vis. Exp.87, doi: 10.3791/51467 (2014).
   Google Scholar
• McEwan C Owen J Stride E et al. Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours. J. Control. Release203, 51–56 (2015).
   PubMed Web of Science ®Google Scholar
• Cavalli R Akhter AK Bisazza A Giustetto P Trotta F Vavia P . Nanosponge formulations as oxygen delivery systems. Int. J. Pharm.402 (1), 254–257 (2010).
   PubMedGoogle Scholar
• Klegerman ME Wassler M Huang SL et al. Liposomal modular complexes for simultaneous targeted delivery of bioactive gases and therapeutics. J. Control. Release142, 326–33 (2010).
   PubMed Web of Science ®Google Scholar
• Cavalli R Bisazza A Rolfo A et al. Ultrasound-mediated oxygen delivery from chitosan nanobubbles. Int. J. Pharm.378 (1–2), 215–217 (2009).
   PubMed Web of Science ®Google Scholar
• Khadjavi A Magnetto C Panariti A et al. Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: new insights for chronic wound healing. Toxicol. Appl. Pharmacol.286 (3), 198–206 (2015).
   PubMed Web of Science ®Google Scholar
• Aryal M Arvanitis CD Alexander PM et al. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. Adv. Drug Deliv. Rev.72, 94–109 (2014).
   PubMed Web of Science ®Google Scholar
• Cavalli R Argenziano M Banche G et al. Nanotechnology and infection: vancomycin–loaded dextran-shelled/perfluoropentane-containing nanobubbles as topical skin-friendly antibacterial vector. Presented at : Second Conference on Nanotechnology for Biological and Biomedical Applications. Trieste, Italy, 14–18 October 2013.
   Google Scholar
• Azagury A Khoury L Enden G et al. Ultrasound mediated transdermal drug delivery. Adv. Drug Deliv. Rev.72, 127–143 (2014).
   PubMed Web of Science ®Google Scholar
• Lammers T Aime S Hennink WE Storm G Kiessling F . Theranostic nanomedicina. Acc. Chem. Res.44 (10), 1029–1038 (2011).
   PubMed Web of Science ®Google Scholar
• Terreno E Uggeri F Aime S . Image guided therapy: the advent of theranostic agents. J. Control. Release161 (2), 328–337 (2012).
   PubMed Web of Science ®Google Scholar
• Kelkar SS Reineke TM . Theranostics: combining imaging and therapy. Bioconjugate Chem.22 (10), 1879–1903 (2011).
   PubMed Web of Science ®Google Scholar
• Shi D . Integrated multifunctional nanosystems for medical diagnosis and treatment. Adv Funct. Mater.19 (21), 3356–3373 (2009).
   Web of Science ®Google Scholar
• Janib SM Moses AS MacKay JA . Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Deliv. Rev.62 (11), 1052–1063 (2010).
   PubMed Web of Science ®Google Scholar
• Muthu MS Feng S . Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success. Expert Opin. Drug Deliv.10 (2), 151–155 (2013).
   PubMed Web of Science ®Google Scholar
• Yin T Wang P Zheng R . Nanobubbles for enhanced ultrasound imaging of tumors. Int. J. Nanomed.7, 895–904 (2012).
   PubMed Web of Science ®Google Scholar
• Ao M Wang Z Ran H et al. Gd-DTPA-loaded PLGA microbubbles as both ultrasound contrast agent and MRI contrast agent‐‐a feasibility research. J. Biomed. Mater. Res. Part B Appl. Biomater.93B (2), 551–556 (2010).
   Web of Science ®Google Scholar
• Cavalli R Argenziano M Vigna E et al. Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents. Colloids Surf. B Biointerfaces129, 39–46 (2015).
   PubMed Web of Science ®Google Scholar
• Unga J Hashida M . Ultrasound induced cancer immunotherapy. Adv. Drug Deliv. Rev.72, 144–153 (2014).
   PubMed Web of Science ®Google Scholar
• Dewitte H Van Lint S Heirman C et al. The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy. J. Control. Release194, 28–36 (2014).
   PubMed Web of Science ®Google Scholar
• Oda Y Suzuki R Otake S et al. Prophylactic immunization with Bubble liposomes and ultrasound-treated dendritic cells provided a four-fold decrease in the frequency of melanoma lung metastasis. J. Control. Release160 (2), 362–366 (2012).
   PubMed Web of Science ®Google Scholar