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WIREs Nanomed Nanobiotechnol

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Multimodal micro, nano, and size conversion ultrasound agents for imaging and therapy

Advanced Review

Elizabeth Huynh, Maneesha A. Rajora, Gang Zheng

Published Online: Mar 23 2016

DOI: 10.1002/wnan.1398

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Ultrasound (US) is one of the most commonly used clinical imaging techniques. However, the use of US and US‐based intravenous agents extends far beyond imaging. In particular, there has been a surge in the fabrication of multimodality US contrast agents and theranostic US agents for cancer imaging and therapy. The unique interaction of US waves with microscale and nanoscale agents has attracted much attention in the development of contrast agents and drug‐delivery vehicles. The dimensions of the agent not only dictate how it behaves in vivo, but also how it interacts with US for imaging and drug delivery. Furthermore, these agents are also unique due to their ability to convert from the nanoscale to the microscale and vice versa, having imaging and therapeutic utility in both dimensions. Here, we review multimodality and multifunctional US‐based agents, according to their size, and also highlight recent developments in size conversion US agents. WIREs Nanomed Nanobiotechnol 2016, 8:796–813. doi: 10.1002/wnan.1398 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Schematic representations of nano‐ and microscale agents. (a) Nanoscale agents are able to extravasate out of the blood vessels into the tumor tissue due to the enhanced permeability and retention (EPR) effect. (b) Microscale agents are confined within the boundaries of blood vessels due to their large size. (c) Different strategies for developing multifunctional US‐based agents, where small molecules or nanoparticles of an additional functionality that can be tethered, adsorbed, encapsulated, or embedded into the US‐based agent.

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Size conversion of porphyrin microbubbles to nanoparticles. (a) Schematic of porphyrin microbubbles that convert to nanoparticles upon sonication with low frequency US. (b) Light microscopy image of porphyrin microbubbles and a transmission electron micrograph of porphyrin nanoparticles after sonication. (c) Multimodal imaging of the porphyrin microbubbles and the resulting nanoparticles in a gel phantom imaged with US, photoacoustic, and fluorescence imaging. Samples: (1) phosphate‐buffered saline, (2) porphyrin microbubbles without applying ultrasound pulses (zero pulses), and after applying (3) 1 pulse, (4) 2 pulses and (5) 10 pulses. (d) Delivery of porphyrin nanoparticles into a KB tumor xenograft in a mouse via the conversion of porphyrin microbubbles to nanoparticles. (Reprinted with permission from Ref . Copyright 2015 Macmillan Publishers Limited)

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Size conversion of porphyrin nanodroplets to microbubbles. (a) Schematic of a porphyrin nanodroplet and its conversion to a microbubble via the absorption of US energy or laser irradiation. (B) Cryo transmission electron micrograph of a porphyrin nanodroplet. (c) Size distribution of nanodroplets fabricated without the porphyrin and porphyrin nanodroplets with the addition of laser irradiation. (Reprinted with permission from Ref . Copyright 2015 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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Size conversion of Indocyanine green (ICG) nanodroplets to microbubbles using an optical trigger. Nanodroplets in solution before (laser off) and after (laser on) laser irradiation. Three samples were compared of nanodroplets in water, ICG‐loaded nanodroplets in water, and pure nanodroplets in an aqueous solution of ICG (a–c). Only the samples with ICG loaded into the core of the nanodroplets underwent conversion to microbubbles upon laser irradiation. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society)

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Size conversion of India ink nanodroplets to microbubbles using an optical trigger. (a) Schematic of the fabrication process of India ink nanodroplets. (b) Schematic of the resulting nanodroplet encapsulating India ink. (c) Scanning electron microscopy image of India ink nanodroplets. (d) Bright‐field optical microscopy image of nanodroplets prior to laser irradiation and the formation of microbubbles after laser irradiation. (e) Ultrasound image of a mouse tumor xenograft injected intratumorally with India ink nanodroplets, pre‐ and postlaser irradiation. Mice were injected with nanodroplets without India ink, free India ink, or India ink‐loaded nanoplets. The conversion of nanodroplets to microbubbles was only observed in animals injected with India ink nanodroplets and laser irradiation. (Reprinted with permission from Ref . Copyright 2014 Ivyspring International Publisher)

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Size conversion of doxorubicin‐loaded nanodroplets. Optical images of doxorubicin‐loaded nanodroplets in a plastic capillary. (a–d) Demonstrated the first heating and cooling cycle of the nanodroplets, where the nanodroplets in (a) grow to nanobubbles and coalesce to form microbubbles after heating. Upon cooling in (d), the microbubbles shrink to microdroplets, but the original size of the droplet is not restored due to coalescence in the initial heating cycle. (e–f) Demonstrated the second heating cycle of the droplets and their response to heating, resulting in their expansion into microbubbles. (Reprinted with permission from Ref . Copyright 2008 Elsevier)

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Doxorubicin‐loaded nanodroplets. (a) Schematic of doxorubicin‐loaded nanodroplets and their extravasation from the vasculature into the tumor tissue. Accumulation of nanodroplets in the tumor tissue results in coalescence to form microbubbles. (b) In vivo demonstration of nanodroplets in a human breast cancer xenograft in a mouse before (left) and 4 h after (right) intratumor injection of nanodroplets. (Reprinted with permission from Ref . Copyright 2008 Elsevier)

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Porphyrin microbubbles for ultrasound (US), photoacoustic and fluorescence imaging. (a) Schematic of trimodality porphyrin microbubbles. (b) In vivo US and photoacoustic images of porphyrin microbubbles before and after intravenous injection in a KB tumor xenograft bearing mouse. (c) Ex vivo fluorescence images of the tumor after injection of porphyrin microbubbles compared to unimodal microbubbles without porphyrin. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society)

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Trimodal ^99mTc‐superparamagnetic iron oxide nanoparticle (SPION)‐polyvinyl alcohol (PVA) microbubbles used to evaluate microbubble biodistribution in rats. (a) Negative enhancement of the healthy rat liver is visible in the T₂*‐weighted magnetic resonance imaging (MRI) scans relative to the preinjection scan (a) at 2 h (c) and 24 h (e) post intravenous microbubble injection. SPECT/CT images at 2 h (b) and 24 h (d) demonstrate a redistribution of the microbubble components from the lungs to the liver. (Reprinted with permission from Ref . Copyright 2013 Springer)

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References

Moghimi, SM, Porter, CJ, Muir, IS, Illum, L, Davis, SS. Non‐phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem Biophys Res Commun 1991, 177:861–866.
Roerdink, F, Regts, J, Van Leeuwen, B, Scherphof, G. Intrahepatic uptake and processing of intravenously injected small unilamellar phospholipid vesicles in rats. Biochim Biophys Acta 1984, 770:195–202.
Matsumura, Y, Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 1986, 46:6387–6392.
Wei, K, Jayaweera, AR, Firoozan, S, Linka, A, Skyba, DM, Kaul, S. Quantification of myocardial blood flow with ultrasound‐induced destruction of microbubbles administered as a constant venous infusion. Circulation 1998, 97:473–483.
Burns, PN, Wilson, SR, Simpson, DH. Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast. Invest Radiol 2000, 35:58–71.
Jayaweera, AR, Edwards, N, Glasheen, WP, Villanueva, FS, Abbott, RD, Kaul, S. In vivo myocardial kinetics of air‐filled albumin microbubbles during myocardial contrast echocardiography. Comparison with radiolabeled red blood cells. Circ Res 1994, 74:1157–1165.
Wilson, SR, Burns, PN. Microbubble‐enhanced US in body imaging: what role? Radiology 2010, 257:24–39.
Dindyal, S, Kyriakides, C. Ultrasound microbubble contrast and current clinical applications. Recent Pat Cardiovasc Drug Discov 2011, 6:27–41.
Moriyasu, F, Itoh, K. Efficacy of perflubutane microbubble‐enhanced ultrasound in the characterization and detection of focal liver lesions: phase 3 multicenter clinical trial. AJR Am J Roentgenol 2009, 193:86–95.
Weskott, HP. Emerging roles for contrast‐enhanced ultrasound. Clin Hemorheol Microcirc 2008, 40:51–71.
Huynh, E, Zheng, G. Engineering multifunctional nanoparticles: all‐in‐one versus one‐for‐all. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2013, 5:250–265.
Jin, Y, Jia, C, Huang, SW, O`Donnell, M, Gao, X. Multifunctional nanoparticles as coupled contrast agents. Nat Commun 2010, 1:41.
Kabalnov, A, Bradley, J, Flaim, S, Klein, D, Pelura, T, Peters, B, Otto, S, Reynolds, J, Schutt, E, Weers, J. Dissolution of multicomponent microbubbles in the bloodstream: 2. Experiment. Ultrasound Med Biol 1998, 24:751–760.
Kabalnov, A, Klein, D, Pelura, T, Schutt, E, Weers, J. Dissolution of multicomponent microbubbles in the bloodstream: 1. Theory. Ultrasound Med Biol 1998, 24:739–749.
Chomas, JE, Dayton, P, May, D, Ferrara, K. Threshold of fragmentation for ultrasonic contrast agents. J Biomed Opt 2001, 6:141–150.
Burns, PN, Hope Simpson, D, Averkiou, MA. Nonlinear imaging. Ultrasound Med Biol 2000, 26(Suppl 1):S19–22.
Lentacker, I, De Cock, I, Deckers, R, De Smedt, SC, Moonen, CT. Understanding ultrasound induced sonoporation: definitions and underlying mechanisms. Adv Drug Deliv Rev 2014, 72:49–64.
van Wamel, A, Bouakaz, A, Versluis, M, de Jong, N. Micromanipulation of endothelial cells: ultrasound‐microbubble‐cell interaction. Ultrasound Med Biol 2004, 30:1255–1258.
van Wamel, A, Kooiman, K, Harteveld, M, Emmer, M, ten Cate, FJ, Versluis, M, de Jong, N. Vibrating microbubbles poking individual cells: drug transfer into cells via sonoporation. J Control Release 2006, 112:149–155.
Juffermans, LJ, van Dijk, A, Jongenelen, CA, Drukarch, B, Reijerkerk, A, de Vries, HE, Kamp, O, Musters, RJ. Ultrasound and microbubble‐induced intra‐ and intercellular bioeffects in primary endothelial cells. Ultrasound Med Biol 2009, 35:1917–1927.
Kumon, RE, Aehle, M, Sabens, D, Parikh, P, Kourennyi, D, Deng, CX. Ultrasound‐induced calcium oscillations and waves in Chinese hamster ovary cells in the presence of microbubbles. Biophys J 2007, 93:L29–31.
Kumon, RE, Aehle, M, Sabens, D, Parikh, P, Han, YW, Kourennyi, D, Deng, CX. Spatiotemporal effects of sonoporation measured by real‐time calcium imaging. Ultrasound Med Biol 2009, 35:494–506.
Apodaca, G. Modulation of membrane traffic by mechanical stimuli. Am J Physiol Renal Physiol 2002, 282:F179–190.
Lionetti, V, Fittipaldi, A, Agostini, S, Giacca, M, Recchia, FA, Picano, E. Enhanced caveolae‐mediated endocytosis by diagnostic ultrasound in vitro. Ultrasound Med Biol 2009, 35:136–143.
Tachibana, K, Uchida, T, Ogawa, K, Yamashita, N, Tamura, K. Induction of cell‐membrane porosity by ultrasound. Lancet 1999, 353:1409.
Postema, M, van Wamel, A, Lancee, CT, de Jong, N. Ultrasound‐induced encapsulated microbubble phenomena. Ultrasound Med Biol 2004, 30:827–840.
Postema, M, van Wamel, A, ten Cate, FJ, de Jong, N. High‐speed photography during ultrasound illustrates potential therapeutic applications of microbubbles. Med Phys 2005, 32:3707–3711.
Tran, TA, Roger, S, Le Guennec, JY, Tranquart, F, Bouakaz, A. Effect of ultrasound‐activated microbubbles on the cell electrophysiological properties. Ultrasound Med Biol 2007, 33:158–163.
Frenkel, V. Ultrasound mediated delivery of drugs and genes to solid tumors. Adv Drug Deliv Rev 2008, 60:1193–1208.
Geis, NA, Katus, HA, Bekeredjian, R. Microbubbles as a vehicle for gene and drug delivery: current clinical implications and future perspectives. Curr Pharm Des 2012, 18:2166–2183.
Mayer, CR, Geis, NA, Katus, HA, Bekeredjian, R. Ultrasound targeted microbubble destruction for drug and gene delivery. Expert Opin Drug Deliv 2008, 5:1121–1138.
Ferrara, K, Pollard, R, Borden, M. Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. Annu Rev Biomed Eng 2007, 9:415–447.
Klibanov, AL. Microbubble contrast agents: targeted ultrasound imaging and ultrasound‐assisted drug‐delivery applications. Invest Radiol 2006, 41:354–362.
Lum, AF, Borden, MA, Dayton, PA, Kruse, DE, Simon, SI, Ferrara, KW. Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles. J Control Release 2006, 111:128–134.
Bekeredjian, R, Chen, S, Frenkel, PA, Grayburn, PA, Shohet, RV. Ultrasound‐targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation 2003, 108:1022–1026.
Korpanty, G, Chen, S, Shohet, RV, Ding, J, Yang, B, Frenkel, PA, Grayburn, PA. Targeting of VEGF‐mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles. Gene Ther 2005, 12:1305–1312.
Bekeredjian, R, Chen, S, Pan, W, Grayburn, PA, Shohet, RV. Effects of ultrasound‐targeted microbubble destruction on cardiac gene expression. Ultrasound Med Biol 2004, 30:539–543.
Koike, H, Tomita, N, Azuma, H, Taniyama, Y, Yamasaki, K, Kunugiza, Y, Tachibana, K, Ogihara, T, Morishita, R. An efficient gene transfer method mediated by ultrasound and microbubbles into the kidney. J Gene Med 2005, 7:108–116.
Shimamura, M, Sato, N, Taniyama, Y, Kurinami, H, Tanaka, H, Takami, T, Ogihara, T, Tohyama, M, Kaneda, Y, Morishita, R. Gene transfer into adult rat spinal cord using naked plasmid DNA and ultrasound microbubbles. J Gene Med 2005, 7:1468–1474.
Tartis, MS, Kruse, DE, Zheng, H, Zhang, H, Kheirolomoom, A, Marik, J, Ferrara, KW. Dynamic microPET imaging of ultrasound contrast agents and lipid delivery. J Control Release 2008, 131:160–166.
Barrefelt AAB, TB, Egri, G, Aspelin, P, Olsson, A, Oddo, L, Margheritelli, S, Caidahl, K, Paradossi, G, Dahne, L, Axelsson, R, et al. Multimodality imaging using SPECT/CT and MRI and ligand functionalized 99mTc‐labeled magnetic microbubbles. EJNMMI Res 2013, 3:1–14.
Barrefelt, A, Zhao, Y, Larsson, MK, Egri, G, Kuiper, RV, Hamm, J, Saghafian, M, Caidahl, K, Brismar, TB, Aspelin, P, et al. Fluorescence labeled microbubbles for multimodal imaging. Biochem Biophys Res Commun 2015, 464:737–742.
Yang, F, Li, Y, Chen, Z, Zhang, Y, Wu, J, Gu, N. Superparamagnetic iron oxide nanoparticle‐embedded encapsulated microbubbles as dual contrast agents of magnetic resonance and ultrasound imaging. Biomaterials 2009, 30:3882–3890.
Moghissi, K, Dixon, K. Photodynamic therapy (PDT) in esophageal cancer: a surgical view of its indications based on 14 years experience. Technol Cancer Res Treat 2003, 2:319–326.
Xu, B, Lu, R, Dou, H, Tao, K, Sun, K, Qiu, Y, Ding, J, Zhang, D, Li, J, Shi, W, et al. Exploring the structure–property relationships of ultrasonic/MRI dual imaging magnetite/PLA microbubbles: magnetite@Cavity versus magnetite@Shell systems. Colloid Polym Sci 2012, 290:1617–1626.
Teraphongphom, N, Chhour, P, Eisenbrey, JR, Naha, PC, Witschey, WR, Opasanont, B, Jablonowski, L, Cormode, DP, Wheatley, MA. Nanoparticle loaded polymeric microbubbles as contrast agents for multimodal imaging. Langmuir 2015, 31:11858–11867.
Ao, M, Wang, Z, Ran, H, Guo, D, Yu, J, Li, A, Chen, W, Wu, W, Zheng, Y. Gd‐DTPA‐loaded PLGA microbubbles as both ultrasound contrast agent and MRI contrast agent—a feasibility research. J Biomed Mater Res B Appl Biomater 2010, 93:551–556.
Mlkvy, P, Makovnik, P, Majek, J, Slezak, P, Kollar, T. Laser and photodynamic therapy for esophageal cancer. Bratisl Lek Listy 2003, 104:90–91.
Liu, Z, Lammers, T, Ehling, J, Fokong, S, Bornemann, J, Kiessling, F, Gatjens, J. Iron oxide nanoparticle‐containing microbubble composites as contrast agents for MR and ultrasound dual‐modality imaging. Biomaterials 2011, 32:6155–6163.
Liu, TY, Wu, MY, Lin, MH, Yang, FY. A novel ultrasound‐triggered drug vehicle with multimodal imaging functionality. Acta Biomater 2013, 9:5453–5463.
Feshitan, JA, Vlachos, F, Sirsi, SR, Konofagou, EE, Borden, MA. Theranostic Gd(III)‐lipid microbubbles for MRI‐guided focused ultrasound surgery. Biomaterials 2012, 33:247–255.
Xu, RX, Huang, J, Xu, JS, Sun, D, Hinkle, GH, Martin, EW, Povoski, SP. Fabrication of indocyanine green encapsulated biodegradable microbubbles for structural and functional imaging of cancer. J Biomed Opt 2009, 14:034020.
Ke, H, Xing, Z, Zhao, B, Wang, J, Liu, J, Guo, C, Yue, X, Liu, S, Tang, Z, Dai, Z. Quantum‐dot‐modified microbubbles with bi‐mode imaging capabilities. Nanotechnology 2009, 20:425105.
Jin, B, Lin, M, Zong, Y, Wan, M, Xu, F, Duan, Z, Lu, T. Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging. Nanotechnology 2015, 26:345601.
Koczera, P, Wu, Z, Fokong, S, Theek, B, Appold, L, Jorge, S, Mockel, D, Liu, Z, Curaj, A, Storm, G, et al. Fluorescently labeled microbubbles for facilitating translational molecular ultrasound studies. Drug Deliv Transl Res 2012, 2:56–64.
Liu, Z, Koczera, P, Doleschel, D, Kiessling, F, Gatjens, J. Versatile synthetic strategies for PBCA‐based hybrid fluorescent microbubbles and their potential theranostic applications to cell labelling and imaging. Chem Commun (Camb) 2012, 48:5142–5144.
Kim, C, Qin, R, Xu, JS, Wang, LV, Xu, R. Multifunctional microbubbles and nanobubbles for photoacoustic and ultrasound imaging. J Biomed Opt 2010, 15:010510.
Jeon, M, Song, W, Huynh, E, Kim, J, Kim, J, Helfield, BL, Leung, BY, Goertz, DE, Zheng, G, Oh, J, et al. Methylene blue microbubbles as a model dual‐modality contrast agent for ultrasound and activatable photoacoustic imaging. J Biomed Opt 2014, 19:16005.
Dove, JD, Murray, TW, Borden, MA. Enhanced photoacoustic response with plasmonic nanoparticle‐templated microbubbles. Soft Matter 2013, 9:7743.
Huynh, E, Lovell, JF, Helfield, BL, Jeon, M, Kim, C, Goertz, DE, Wilson, BC, Zheng, G. Porphyrin shell microbubbles with intrinsic ultrasound and photoacoustic properties. J Am Chem Soc 2012, 134:16464–16467.
Huynh, E, Jin, CS, Wilson, BC, Zheng, G. Aggregate enhanced trimodal porphyrin shell microbubbles for ultrasound, photoacoustic, and fluorescence imaging. Bioconjug Chem 2014, 25:796–801.
Sun, Y, Zheng, Y, Ran, H, Zhou, Y, Shen, H, Chen, Y, Chen, H, Krupka, TM, Li, A, Li, P, et al. Superparamagnetic PLGA‐iron oxide microcapsules for dual‐modality US/MR imaging and high intensity focused US breast cancer ablation. Biomaterials 2012, 33:5854–5864.
Lammers, T, Koczera, P, Fokong, S, Gremse, F, Ehling, J, Vogt, M, Pich, A, Storm, G, van Zandvoort, M, Kiessling, F. Theranostic USPIO‐loaded microbubbles for mediating and monitoring blood–brain barrier permeation. Adv Funct Mater 2015, 25:36–43.
Jiang, C, Li, X, Yan, F, Wang, Z, Jin, Q, Cai, F, Qian, M, Liu, X, Zhang, L, Zheng, H. Microfluidic‐assisted formation of multifunctional monodisperse microbubbles for diagnostics and therapeutics. Micro Nano Lett 2011, 6:417.
Niu, C, Wang, Z, Lu, G, Krupka, TM, Sun, Y, You, Y, Song, W, Ran, H, Li, P, Zheng, Y. Doxorubicin loaded superparamagnetic PLGA‐iron oxide multifunctional microbubbles for dual‐mode US/MR imaging and therapy of metastasis in lymph nodes. Biomaterials 2013, 34:2307–2317.
Moon, H, Kang, J, Sim, C, Kim, J, Lee, H, Chang, JH, Kim, H. Multifunctional theranostic contrast agent for photoacoustics‐ and ultrasound‐based tumor diagnosis and ultrasound‐stimulated local tumor therapy. J Control Release 2015, 218:63–71.
Wang, YH, Liao, AH, Chen, JH, Wang, CR, Li, PC. Photoacoustic/ultrasound dual‐modality contrast agent and its application to thermotherapy. J Biomed Opt 2012, 17:045001.
Ke, H, Wang, J, Dai, Z, Jin, Y, Qu, E, Xing, Z, Guo, C, Yue, X, Liu, J. Gold‐nanoshelled microcapsules: a theranostic agent for ultrasound contrast imaging and photothermal therapy. Angew Chem Int Ed Engl 2011, 50:3017–3021.
Jin, Y, Wang, J, Ke, H, Wang, S, Dai, Z. Graphene oxide modified PLA microcapsules containing gold nanoparticles for ultrasonic/CT bimodal imaging guided photothermal tumor therapy. Biomaterials 2013, 34:4794–4802.
Li, X‐D, Liang, X‐L, Yue, X‐L, Wang, J‐R, Li, C‐H, Deng, Z‐J, Jing, L‐J, Lin, L, Qu, E‐Z, Wang, S‐M, et al. Imaging guided photothermal therapy using iron oxide loaded poly(lactic acid) microcapsules coated with graphene oxide. J Mater Chem B 2014, 2:217–223.
Yin, T, Wang, P, Li, J, Zheng, R, Zheng, B, Cheng, D, Li, R, Lai, J, Shuai, X. Ultrasound‐sensitive siRNA‐loaded nanobubbles formed by hetero‐assembly of polymeric micelles and liposomes and their therapeutic effect in gliomas. Biomaterials 2013, 34:4532–4543.
Yin, T, Wang, P, Li, J, Wang, Y, Zheng, B, Zheng, R, Cheng, D, Shuai, X. Tumor‐penetrating codelivery of siRNA and paclitaxel with ultrasound‐responsive nanobubbles hetero‐assembled from polymeric micelles and liposomes. Biomaterials 2014, 35:5932–5943.
Misra SKG, G, Jensen, TW, Partha, SR, Burdette, EC, Pan, D. Bi‐modal cancer treatment utilizing therapeutic ultrasound and an engineered therapeutic nanobubble. RSC Adv 2015, 5:63839–63845.
Yang, H, Deng, L, Li, T, Shen, X, Yan, J, Zuo, L, Wu, C, Liu, Y. Multifunctional PLGA nanobubbles as theranostic agents: combining doxorubicin and P‐gp siRNA co‐delivery into human breast cancer cells and ultrasound cellular imaging. J Biomed Nanotechnol 2015, 11:2124–2136.
Cavalli, R, Bisazza, A, Trotta, M, Argenziano, M, Civra, A, Donalisio, M, Lembo, D. New chitosan nanobubbles for ultrasound‐mediated gene delivery: preparation and in vitro characterization. Int J Nanomedicine 2012, 7:3309–3318.
Xu, JS, Huang, J, Qin, R, Hinkle, GH, Povoski, SP, Martin, EW, Xu, RX. Synthesizing and binding dual‐mode poly (lactic‐co‐glycolic acid) (PLGA) nanobubbles for cancer targeting and imaging. Biomaterials 2010, 31:1716–1722.
Mai, L, Yao, A, Li, J, Wei, Q, Yuchi, M, He, X, Ding, M, Zhou, Q. Cyanine 5.5 conjugated nanobubbles as a tumor selective contrast agent for dual ultrasound‐fluorescence imaging in a mouse model. PLoS One 2013, 8:e61224.
Yang, H, Cai, W, Xu, L, Lv, X, Qiao, Y, Li, P, Wu, H, Yang, Y, Zhang, L, Duan, Y. Nanobubble‐affibody: novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor. Biomaterials 2015, 37:279–288.
Huang, HY, Liu, HL, Hsu, PH, Chiang, CS, Tsai, CH, Chi, HS, Chen, SY, Chen, YY. A multitheragnostic nanobubble system to induce blood–brain barrier disruption with magnetically guided focused ultrasound. Adv Mater 2015, 27:655–661.
Gao, Z, Kennedy, AM, Christensen, DA, Rapoport, NY. Drug‐loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy. Ultrasonics 2008, 48:260–270.
Ji, G, Yang, J, Chen, J. Preparation of novel curcumin‐loaded multifunctional nanodroplets for combining ultrasonic development and targeted chemotherapy. Int J Pharm 2014, 466:314–320.
Kripfgans, OD, Fowlkes, JB, Miller, DL, Eldevik, OP, Carson, PL. Acoustic droplet vaporization for therapeutic and diagnostic applications. Ultrasound Med Biol 2000, 26:1177–1189.
Rapoport, N, Nam, KH, Gupta, R, Gao, Z, Mohan, P, Payne, A, Todd, N, Liu, X, Kim, T, Shea, J, et al. Ultrasound‐mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions. J Control Release 2011, 153:4–15.
Williams, R, Wright, C, Cherin, E, Reznik, N, Lee, M, Gorelikov, I, Foster, FS, Matsuura, N, Burns, PN. Characterization of submicron phase‐change perfluorocarbon droplets for extravascular ultrasound imaging of cancer. Ultrasound Med Biol 2013, 39:475–489.
Matsunaga, TO, Sheeran, PS, Luois, S, Streeter, JE, Mullin, LB, Banerjee, B, Dayton, PA. Phase‐change nanoparticles using highly volatile perfluorocarbons: toward a platform for extravascular ultrasound imaging. Theranostics 2012, 2:1185–1198.
Rapoport, N. Phase‐shift, stimuli‐responsive perfluorocarbon nanodroplets for drug delivery to cancer. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2012, 4:492–510.
Lin, CY, Javadi, M, Belnap, DM, Barrow, JR, Pitt, WG. Ultrasound sensitive eLiposomes containing doxorubicin for drug targeting therapy. Nanomedicine 2014, 10:67–76.
Wilson, K, Homan, K, Emelianov, S. Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast‐enhanced imaging. Nat Commun 2012, 3:618.
Jian, J, Liu, C, Gong, Y, Su, L, Zhang, B, Wang, Z, Wang, D, Zhou, Y, Xu, F, Li, P, et al. India ink incorporated multifunctional phase‐transition nanodroplets for photoacoustic/ultrasound dual‐modality imaging and photoacoustic effect based tumor therapy. Theranostics 2014, 4:1026–1038.
Hannah, A, Luke, G, Wilson, K, Homan, K, Emelianov, S. Indocyanine green‐loaded photoacoustic nanodroplets: dual contrast nanoconstructs for enhanced photoacoustic and ultrasound imaging. ACS Nano 2014, 8:250–259.
Zhao, Y, Song, W, Wang, D, Ran, H, Wang, R, Yao, Y, Wang, Z, Zheng, Y, Li, P. Phase‐shifted PFH@PLGA/Fe3O4 nanocapsules for MRI/US imaging and photothermal therapy with near‐infrared irradiation. ACS Appl Mater Interfaces 2015, 7:14231–14242.
Paproski, RJ, Forbrich, A, Huynh, E, Chen, J, Lewis, JD, Zheng, G, Zemp, RJ. Porphyrin nanodroplets: sub‐micrometer ultrasound and photoacoustic contrast imaging agents. Small 2015, 12:371–380.
Prabhakar, U, Maeda, H, Jain, RK, Sevick‐Muraca, EM, Zamboni, W, Farokhzad, OC, Barry, ST, Gabizon, A, Grodzinski, P, Blakey, DC. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res 2013, 73:2412–2417.
Huynh, E, Leung, BY, Helfield, BL, Shakiba, M, Gandier, JA, Jin, CS, Master, ER, Wilson, BC, Goertz, DE, Zheng, G. In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging. Nat Nanotechnol 2015, 10:325–332.
Lovell, JF, Jin, CS, Huynh, E, MacDonald, TD, Cao, W, Zheng, G. Enzymatic regioselection for the synthesis and biodegradation of porphysome nanovesicles. Angew Chem Int Ed Engl 2012, 51:2429–2433.
Lovell, JF, Jin, CS, Huynh, E, Jin, H, Kim, C, Rubinstein, JL, Chan, WC, Cao, W, Wang, LV, Zheng, G. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nat Mater 2011, 10:324–332.

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