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      India Ink Incorporated Multifunctional Phase-transition Nanodroplets for Photoacoustic/Ultrasound Dual-modality Imaging and Photoacoustic Effect Based Tumor Therapy

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          Abstract

          The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms—conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic, and ultrasound imaging contrasts, but also a new avenue for photoacoustic effect mediated tumor therapy. Upon pulsed laser illumination above a relatively low energy threshold, liquid-gas phase transition of the INDs has been demonstrated both in vitro and in vivo, offering excellent contrasts for photoacoustic and ultrasound dual-modality imaging. With further increased laser energy, the nanodroplets have been shown to be capable of destructing cancer cells in vivo, presumably due to the photoacoustic effect induced shock-wave generation from the carbon particles of the incorporated India ink. The demonstrated results suggest that the developed multifunctional phase-transition nanodroplets have a great potential for many theranostic biomedical applications, including photoacoustic/ultrasound dual-modality molecular imaging and targeted, localized cancer therapy.

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          Most cited references 38

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          One-step fabrication of supramolecular microcapsules from microfluidic droplets.

          Although many techniques exist for preparing microcapsules, it is still challenging to fabricate them in an efficient and scalable process without compromising functionality and encapsulation efficiency. We demonstrated a simple one-step approach that exploits a versatile host-guest system and uses microfluidic droplets to generate porous microcapsules with easily customizable functionality. The capsules comprise a polymer-gold nanoparticle composite held together by cucurbit[8]uril ternary complexes. The dynamic yet highly stable micrometer-sized structures can be loaded in one step during capsule formation and are amenable to on-demand encapsulant release. The internal chemical environment can be probed with surface enhanced Raman spectroscopy.
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            Biomedical applications of photoacoustic imaging with exogenous contrast agents.

            Photoacoustic imaging is a biomedical imaging modality that provides functional information, and, with the help of exogenous contrast agents, cellular and molecular signatures of tissue. In this article, we review the biomedical applications of photoacoustic imaging assisted with exogenous contrast agents. Dyes, noble metal nanoparticles, and other constructs are contrast agents which absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic response. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications ranging from detection of cancer cells, sentinel lymph nodes, and micrometastasis to angiogenesis to characterization of atherosclerotic plaques. Multi-functional agents have also been developed, which can carry drugs or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents were used to guide and monitor the therapeutic procedures. Overall, photoacoustic imaging shows significant promise in its ability to assist in diagnosis, therapy planning, and monitoring of treatment outcome for cancer, cardiovascular disease, and other pathologies.
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              Protein-assisted fabrication of nano-reduced graphene oxide for combined in vivo photoacoustic imaging and photothermal therapy.

              Theranostic agents are attracting a great deal of attention in personalized medicine. Here, we developed a protein-based, facile method for fabrication of nanosized, reduced graphene oxide (nano-rGO) with high stability and low cytotoxicity. We constructed highly integrated photoacoustic/ultrasonic dual-modality imaging and photothermal therapy platforms, and further demonstrated that the prepared nano-rGO can be used as ready-to-use theranostic agents for both photoacoustic imaging and photothermal therapy without further surface modification. Intravenous administration of nano-rGO in tumor-bearing mice showed rapid and significant photoacoustic signal enhancement in the tumor region, indicating its excellence for passive targeting and photoacoustic imaging. Meanwhile, using a continuous-wave near-infrared laser, cancer cells in vivo were efficiently ablated, due to the photothermal effect of nano-rGO. The results suggest that the nano-rGO with protein-assisted fabrication was well suited for photoacoustic imaging and photothermal therapy of tumor, which is promising for theranostic nanomedicine. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2014
                1 August 2014
                : 4
                : 10
                : 1026-1038
                Affiliations
                1. Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
                2. Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
                3. Research Lab for Biomedical Optics and Molecular Imaging, Shenzhen Key Lab for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
                4. Department of Ultrasound, The Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
                Author notes
                ✉ Corresponding author: Xiyuan Zhou, Tel./fax: +86 23 63693589; E-mail: cb.liu@ 123456siat.ac.cn . Or Liang Song, Tel: +86 755 86392240; E-mail: liang.song@ 123456siat.ac.cn .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov04p1026
                10.7150/thno.9754
                4143943
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                Categories
                Research Paper

                Molecular medicine

                india ink, nanodroplets

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