Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies.

Gold nanoparticles (AuNPs) have exceptional stability against oxidation and therefore will play a significant role in the advancement of clinically useful diagnostic and therapeutic nanomedicines. Despite the huge potential for a new generation of AuNP-based nanomedicinal products, nontoxic AuNP constructs and formulations that can be readily administered site-specifically through the intravenous mode, for diagnostic imaging by computed tomography (CT) or for therapy via various modalities, are still rare. Herein, we report results encompassing: 1) the synthesis and stabilization of AuNPs within the nontoxic phytochemical gum-arabic matrix (GA-AuNPs); 2) detailed in vitro analysis and in vivo pharmacokinetics studies of GA-AuNPs in pigs to gain insight into the organ-specific localization of this new generation of AuNP vector, and 3) X-ray CT contrast measurements of GA-AuNP vectors for potential utility in molecular imaging. Our results demonstrate that naturally occurring GA can be used as a nontoxic phytochemical construct in the production of readily administrable biocompatible AuNPs for diagnostic and therapeutic applications in nanomedicine.

[1]  Philip S Low,et al.  In vitro and in vivo two-photon luminescence imaging of single gold nanorods. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Hsin-Li Chen,et al.  Photosensitive gold-nanoparticle-embedded dielectric nanowires , 2006, Nature materials.

[3]  N. Pillarsetty,et al.  Characterization of supramolecular (H2O)18 water morphology and water-methanol (H2O)15(CH3OH)3 clusters in a novel phosphorus functionalized trimeric amino acid host. , 2003, Journal of the American Chemical Society.

[4]  H. Gali,et al.  Synthese des ersten Biokonjugats aus einem chelatisierenden Bisphosphan und einem Peptid ausgehend von einem neuartigen funktionalisierten Phosphor(III)‐hydrid‐Synthon , 1999 .

[5]  S. Rafla,et al.  Radioactive gold grain implants in recurrent and locally advanced head-and-neck cancers. , 2002, Brachytherapy.

[6]  Yi-Cheng Chen,et al.  DNA-gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. , 2006, Journal of the American Chemical Society.

[7]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[8]  F. Avraham Dilmanian,et al.  Murine EMT-6 Carcinoma: High Therapeutic Efficacy of Microbeam Radiation Therapy , 2003, Radiation research.

[9]  H. Gali,et al.  Design and Development of the First Peptide-Chelating Bisphosphane Bioconjugate from a Novel Functionalized Phosphorus(III) Hydride Synthon. , 1999, Angewandte Chemie.

[10]  C. Mirkin,et al.  Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. , 2002, Science.

[11]  Jan Grimm,et al.  An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles , 2006, Nature materials.

[12]  A. Jayakrishnan,et al.  Preparation and in vitro evaluation of primaquine-conjugated gum arabic microspheres. , 2004, Biomacromolecules.

[13]  Chad A Mirkin,et al.  A gold nanoparticle based approach for screening triplex DNA binders. , 2006, Journal of the American Chemical Society.

[14]  R C Nelson,et al.  Timing of parenchymal enhancement on dual-phase dynamic helical CT of the liver: how long does the hepatic arterial phase predominate? , 1996, AJR. American journal of roentgenology.

[15]  K. Bae,et al.  Gadolinium as a CT contrast agent: assessment in a porcine model. , 1999, Radiology.

[16]  M. Chandrasekhar,et al.  Agarose-stabilized gold nanoparticles for surface-enhanced Raman spectroscopic detection of DNA nucleosides , 2006 .

[17]  S. Cho.  Handbook of Dietary Fiber , 2001 .

[18]  V. De Filippis,et al.  Gold nanoparticles-based protease assay. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Richie,et al.  Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[20]  S. Franzen,et al.  Controlled encapsidation of gold nanoparticles by a viral protein shell. , 2006, Journal of the American Chemical Society.

[21]  J. Baker,et al.  Imaging {Au0-PAMAM} Gold-dendrimer Nanocomposites in Cells , 2002 .

[22]  Raghuraman Kannan,et al.  Nanocompatible chemistry toward fabrication of target-specific gold nanoparticles. , 2006, Journal of the American Chemical Society.

[23]  J F Hainfeld,et al.  Gold nanoparticles: a new X-ray contrast agent. , 2006, The British journal of radiology.

[24]  J. Leykam,et al.  Gum arabic glycoprotein contains glycomodules of both extensin and arabinogalactan-glycoproteins. , 2000, Phytochemistry.

[25]  S. Franzen,et al.  Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. , 2003, Journal of the American Chemical Society.

[26]  Vladimir V Tsukruk,et al.  Freely suspended nanocomposite membranes as highly sensitive sensors , 2004, Nature materials.

[27]  Osman Ratib,et al.  OsiriX: An Open-Source Software for Navigating in Multidimensional DICOM Images , 2004, Journal of Digital Imaging.

[28]  S. Griffey,et al.  Indirect computed tomography lymphography using iodinated nanoparticles: time and dose response in normal canine lymph nodes. , 1995, Academic radiology.

[29]  Eunkeu Oh,et al.  Inhibition assay of biomolecules based on fluorescence resonance energy transfer (FRET) between quantum dots and gold nanoparticles. , 2005, Journal of the American Chemical Society.

[30]  J. Hainfeld,et al.  Nanoparticle Molecular Labels , 2005 .

[31]  Charles R. Szmanda,et al.  Programmable polymer thin film and non-volatile memory device , 2004, Nature materials.

[32]  M. Suarez‐Almazor,et al.  Injectable gold for rheumatoid arthritis. , 1997, The Cochrane database of systematic reviews.

[33]  Chad A. Mirkin,et al.  Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation , 2006, Science.

[34]  O. Al‐Shabanah,et al.  Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice. , 2003, Pharmacological research.

[35]  Sang Hyun Cho,et al.  Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: a preliminary Monte Carlo study , 2005, Physics in medicine and biology.

[36]  J F Hainfeld,et al.  New Frontiers in Gold Labeling: Symposium Overview , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[37]  J F Hainfeld,et al.  New Frontiers in Gold Labeling , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[38]  R Richards-Kortum,et al.  Optical Systems for in Vivo Molecular Imaging of Cancer , 2003, Technology in cancer research & treatment.

[39]  A. Hassan,et al.  Prevention of hepatic metastases by intravenous radioactive gold. , 1978, Cancer research.

[40]  G. Gazelle,et al.  Hepatic imaging with iodinated nanoparticles: a comparison with iohexol in rabbits. , 1995, Academic radiology.

[41]  L. Hedlund,et al.  A liposomal nanoscale contrast agent for preclinical CT in mice. , 2006, AJR. American journal of roentgenology.

[42]  G. Phillips,et al.  The molecular characterisation of the polysaccharide gum from Acacia senegal , 1993 .

[43]  Kee Suk Ryu,et al.  A modular microfluidic architecture for integrated biochemical analysis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Peter A. Williams,et al.  Characterization of commercial samples of gum arabic , 1993 .

[45]  K. Katti,et al.  198Au-labeled hydroxymethyl phosphines as models for potential therapeutic pharmaceuticals. , 1998, Nuclear medicine and biology.

[46]  N. Pillarsetty,et al.  In vitro and in vivo antitumor properties of tetrakis((trishydroxy- methyl)phosphine)gold(I) chloride. , 2003, Journal of medicinal chemistry.

[47]  J. Hainfeld,et al.  The use of gold nanoparticles to enhance radiotherapy in mice. , 2004, Physics in medicine and biology.

[48]  Huixiang Li,et al.  Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[49]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[50]  E. Nothnagel,et al.  Cell and Developmental Biology of Arabinogalactan-Proteins , 2000, Springer US.

[51]  G. Phillips,et al.  A review of recent developments on the regulatory, structural and functional aspects of gum arabic. , 1997 .

[52]  Sergiy Minko,et al.  Nanosensors based on responsive polymer brushes and gold nanoparticle enhanced transmission surface plasmon resonance spectroscopy. , 2004, Journal of the American Chemical Society.

[53]  R D Nawfel,et al.  Contrast-detail curves for liver CT. , 1992, Medical physics.

[54]  Ivan Amato,et al.  Nanotechnologists Seek Biological Niches , 2005, Cell.