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      Mn-porphyrin conjugated Au nanoshells encapsulating doxorubicin for potential magnetic resonance imaging and light triggered synergistic therapy of cancer.

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          Abstract

          A theranostic agent was successfully fabricated by the formation of Au nanoshell around poly(lactic acid) nanoparticles entrapping doxorubicin, followed by linking a Mn-porphyrin derivative on the Au shell surface through polyethylene glycol. The resulted agent exhibited excellent colloidal stability and long blood circulation time due to introducing polyethylene glycol. The grafting Mn-porphyrin onto the nanoparticle surface endowed a greatly improved relaxivity (r1 value of 22.18 mM(-1)s(-1) of Mn(3+)), favorable for accurate cancer diagnosing and locating the tumor site to guide the external near infrared (NIR) laser irradiation for photothermal ablation of tumors. The in vitro experiments confirmed that the agent exhibited an efficient photohyperthermia and a light triggered and stepwise release behavior of doxorubicin due to the high NIR light absorption coefficient of Au nanoshell. The in vivo experiments showed that the combination of chemotherapy and photothermal therapy through such theranostic agent offered a synergistically improved therapeutic outcome compared with either therapy alone, making it a promising approach for cancer therapy. Therefore, such theranostic agent can be developed as a smart and promising nanosystemplatform that integrates multiple capabilities for both effective contrast enhanced magnetic resonance imaging and synergistic therapy.

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          Most cited references39

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          Gold nanocages: synthesis, properties, and applications.

          Noble-metal nanocages comprise a novel class of nanostructures possessing hollow interiors and porous walls. They are prepared using a remarkably simple galvanic replacement reaction between solutions containing metal precursor salts and Ag nanostructures prepared through polyol reduction. The electrochemical potential difference between the two species drives the reaction, with the reduced metal depositing on the surface of the Ag nanostructure. In our most studied example, involving HAuCl(4) as the metal precursor, the resultant Au is deposited epitaxially on the surface of the Ag nanocubes, adopting their underlying cubic form. Concurrent with this deposition, the interior Ag is oxidized and removed, together with alloying and dealloying, to produce hollow and, eventually, porous structures that we commonly refer to as Au nanocages. This approach is versatile, with a wide range of morphologies (e.g., nanorings, prism-shaped nanoboxes, nanotubes, and multiple-walled nanoshells or nanotubes) available upon changing the shape of the initial Ag template. In addition to Au-based structures, switching the metal salt precursors to Na(2)PtCl(4) and Na(2)PdCl(4) allows for the preparation of Pt- and Pd-containing hollow nanostructures, respectively. We have found that changing the amount of metal precursor added to the suspension of Ag nanocubes is a simple means of tuning both the composition and the localized surface plasmon resonance (LSPR) of the metal nanocages. Using this approach, we are developing structures for biomedical and catalytic applications. Because discrete dipole approximations predicted that the Au nanocages would have large absorption cross-sections and because their LSPR can be tuned into the near-infrared (where the attenuation of light by blood and soft tissue is greatly reduced), they are attractive materials for biomedical applications in which the selective absorption of light at great depths is desirable. For example, we have explored their use as contrast enhancement agents for both optical coherence tomography and photoacoustic tomography, with improved performance observed in each case. Because the Au nanocages have large absorption cross-sections, they are also effective photothermal transducers; thus, they might provide a therapeutic effect through selective hyperthermia-induced killing of targeted cancer cells. Our studies in vitro have illustrated the feasibility of applying this technique as a less-invasive form of cancer treatment.
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            Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles.

            In this work, a nanoscale reduced graphene oxide-iron oxide nanoparticle (RGO-IONP) complex is noncovalently functionalized with polyethylene glycol (PEG), obtaining a RGO-IONP-PEG nanocomposite with excellent physiological stability, strong NIR optical absorbance, and superparamagnetic properties. Using this theranostic nanoprobe, in-vivo triple modal fluorescence, photoacoustic, and magnetic resonance imaging are carried out, uncovering high passive tumor targeting, which is further used for effective photothermal ablation of tumors in mice. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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              In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice.

              Graphene has emerged as interesting nanomaterials with promising applications in a range of fields including biomedicine. In this work, for the first time we study the long-term in vivo biodistribution of (125)I-labeled nanographene sheets (NGS) functionalized with polyethylene glycol (PEG) and systematically examine the potential toxicity of graphene over time. Our results show that PEGylated NGS mainly accumulate in the reticuloendothelial system (RES) including liver and spleen after intravenous administration and can be gradually cleared, likely by both renal and fecal excretion. PEGylated NGS do not cause appreciable toxicity at our tested dose (20 mg/kg) to the treated mice in a period of 3 months as evidenced by blood biochemistry, hematological analysis, and histological examinations. Our work greatly encourages further studies of graphene for biomedical applications.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                Ivyspring International Publisher
                1838-7640
                1838-7640
                2014
                : 4
                : 9
                Affiliations
                [1 ] 1. Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China. ; 2. School of Life Science and Technology. Harbin Institute of Technology, Harbin 150080, China.
                [2 ] 1. Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
                [3 ] 2. School of Life Science and Technology. Harbin Institute of Technology, Harbin 150080, China.
                Article
                thnov04p0858
                10.7150/thno.8818
                4107288
                25057312
                a4febb7b-5b0e-4e79-ab75-edeedae85f29
                History

                Au nanoshell,chemotherapy,magnetic resonance imaging.,photothermal therapy,porphyrin

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