Near‐Infrared Fluorescent Silica‐Coated Gold Nanoparticle Clusters for X‐Ray Computed Tomography/Optical Dual Modal Imaging of the Lymphatic System

Lymph nodes (LNs) are often removed to prevent the spread of cancer because they are frequently the first site of metastases. However, the enucleation of LNs requires difficult operative techniques and lymphedema can result as a complication. Although lymphedema can be cured by anastomosis of a lymph vessel (LV) to a vein, the operative procedure is extremely difficult because LNs and LVs are too small and indistinct to be identified. Therefore, visualization of LNs and LVs is important. The combination of X-ray computed tomography (CT) and fluorescence imaging, CT/fluorescence dual modal imaging, enables the visualization of LNs and LVs before and during surgery. To accomplish this, near-infrared fluorescent silica-coated gold nanoparticle clusters (Au@SiO₂) with a high X-ray absorption coefficient are synthesized. Both fluorescence imaging and CT show that the Au@SiO₂ nanoparticles gradually accumulate in LNs through LVs. CT determines the location and size of the LNs and LVs without dissection, and fluorescence imaging facilitates their identification. The Au@SiO₂ nanoparticles have neither hepatotoxicity nor nephrotoxicity. The results demonstrate that CT/fluorescence dual modal imaging using Au@SiO₂ nanoparticles provides anatomical information, including the location and size of LNs and LVs for determining a surgery plan, and provides intraoperative visualization of LNs and LVs to facilitate the operation.

[1]  Catherine J. Murphy,et al.  Seed-Mediated Synthesis of Gold Nanorods: Role of the Size and Nature of the Seed , 2004 .

[2]  Lehui Lu,et al.  A high-performance ytterbium-based nanoparticulate contrast agent for in vivo X-ray computed tomography imaging. , 2012, Angewandte Chemie.

[3]  Kemin Wang,et al.  In vivo near-infrared fluorescence imaging of cancer with nanoparticle-based probes. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[4]  Daniel A. Heller,et al.  Treating metastatic cancer with nanotechnology , 2011, Nature Reviews Cancer.

[5]  Samuel Woojoo Jun,et al.  Large-scale synthesis of bioinert tantalum oxide nanoparticles for X-ray computed tomography imaging and bimodal image-guided sentinel lymph node mapping. , 2011, Journal of the American Chemical Society.

[6]  A. M. Rush,et al.  X-ray computed tomography imaging of breast cancer by using targeted peptide-labeled bismuth sulfide nanoparticles. , 2011, Angewandte Chemie.

[7]  Younan Xia,et al.  Inorganic nanoparticle-based contrast agents for molecular imaging. , 2010, Trends in molecular medicine.

[8]  A. S. Moses,et al.  Imaging and drug delivery using theranostic nanoparticles. , 2010, Advanced drug delivery reviews.

[9]  Toshio Matsumoto,et al.  Near‐Infrared Fluorescent Silica/Porphyrin Hybrid Nanorings for In Vivo Cancer Imaging , 2012 .

[10]  Nicolas Anton,et al.  Inorganic Nanoparticles Based Contrast Agents for X‐ray Computed Tomography , 2012, Advanced healthcare materials.

[11]  D. Hammer,et al.  In vivo fluorescence imaging: a personal perspective. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[12]  Lehui Lu,et al.  Hybrid BaYbF5 Nanoparticles: Novel Binary Contrast Agent for High‐Resolution in Vivo X‐ray Computed Tomography Angiography , 2012, Advanced healthcare materials.

[13]  Tristan Barrett,et al.  Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. , 2007, Nano letters.

[14]  S. Gambhir,et al.  Molecular imaging in living subjects: seeing fundamental biological processes in a new light. , 2003, Genes & development.

[15]  Michihiro Nakamura,et al.  Silica-porphyrin hybrid nanotubes for in vivo cell tracking by near-infrared fluorescence imaging. , 2012, Chemical communications.

[16]  Raoul Kopelman,et al.  Targeted gold nanoparticles enable molecular CT imaging of cancer. , 2008, Nano letters.

[17]  Michael J Sailor,et al.  Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. , 2009, Cancer research.

[18]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[19]  Lehui Lu,et al.  Large‐Scale Synthesis of Bi2S3 Nanodots as a Contrast Agent for In Vivo X‐ray Computed Tomography Imaging , 2011, Advanced materials.

[20]  Jinwoo Cheon,et al.  Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. , 2008, Accounts of chemical research.

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

[22]  C. Bucana,et al.  Biochemical, morphological, and ultrastructural studies on the uptake of liposomes by murine macrophages. , 1981, Cancer research.

[23]  Z. Fayad,et al.  A fluorescent, paramagnetic and PEGylated gold/silica nanoparticle for MRI, CT and fluorescence imaging. , 2010, Contrast Media & Molecular Imaging.

[24]  H. Zentgraf,et al.  Anti-CD4-targeted gold nanoparticles induce specific contrast enhancement of peripheral lymph nodes in X-ray computed tomography of live mice. , 2010, Nano letters.