Abstract
Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging1,2,3,4,5,6,7,8, both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots9,10,11,12, magnetic13 and magnetofluorescent nanoparticles14,15, gold nanoparticles and nanoshells16,17,18,19, among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi2S3 nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi3+), high X-ray absorption (fivefold better than iodine), very long circulation times (>2 h) in vivo and an efficacy/safety profile comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi2S3 nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Weissleder, R. & Ntziachristos, V. Shedding light onto live molecular targets. Nature Med. 9, 123–128 (2003).
Ntziachristos, V., Ripoll, J., Wang, L. V. & Weissleder, R. Looking and listening to light: the evolution of whole-body photonic imaging. Nature Biotechnol. 23, 313–320 (2005).
Jaffer, F. A. & Weissleder, R. Molecular imaging in the clinical arena. Jama 293, 855–862 (2005).
Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nature Rev. Cancer 5, 161–171 (2005).
Whitesides, G. M. The ‘right’ size in nanobiotechnology. Nature Biotechnol. 21, 1161–1165 (2003).
Alivisatos, A. P., Gu, W. & Larabell, C. Quantum dots as cellular probes. Annu. Rev. Biomed. Eng. 7, 1–22 (2005).
Medintz, I. L., Uyeda, H. T., Goldman, E. R. & Mattoussi, H. Quantum dot bioconjugates for imaging, labelling and sensing. Nature Mater. 4, 435–446 (2005).
Rosi, N. L. & Mirkin, C. A. Nanostructures in biodiagnostics. Chem. Rev. 105, 1547–1562 (2005).
Bruchez, M. Jr, Moronne, M., Gin, P., Weiss, S. & Alivisatos, A. P. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013–2016 (1998).
Chan, W. C. & Nie, S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018 (1998).
Dubertret, B. et al. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759–1762 (2002).
Kim, S. et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nature Biotechnol. 22, 93–97 (2004).
Shen, T., Weissleder, R., Papisov, M., Bogdanov, A. Jr & Brady, T. J. Monocrystalline iron oxide nanocompounds (MION): physicochemical properties. Magn. Reson. Med. 29, 599–604 (1993).
Kircher, M. F., Mahmood, U., King, R. S., Weissleder, R. & Josephson, L. A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res. 63, 8122–8125 (2003).
Santra, S., Yang, H., Holloway, P. H., Stanley, J. T. & Mericle, R. A. Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS:Mn/ZnS quantum dots: a multifunctional probe for bioimaging. J. Am. Chem. Soc. 127, 1656–1657 (2005).
El-Sayed, I. H., Huang, X. & El-Sayed, M. A. Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Lett. 5, 829–834 (2005).
Loo, C., Lowery, A., Halas, N., West, J. & Drezek, R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 5, 709–711 (2005).
Chen, J. et al. Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett. 5, 473–477 (2005).
Hainfeld, J. F., Slatkin, D. N. & Smilowitz, H. M. The use of gold nanoparticles to enhance radiotherapy in mice. Phys. Med. Biol. 49, N309–N315 (2004).
Bühler, V. Kollidon® Polyvinylpyrrolidone for the Pharmaceutical Industry 9–125 (BASF Fine Chemicals, Ludwigshafen, 1998).
Sun, Y. G. & Xia, Y. N. Shape-controlled synthesis of gold and silver nanoparticles. Science 298, 2176–2179 (2002).
Teranishi, T., Hosoe, M., Tanaka, T. & Miyake, M. Size control of monodispersed Pt nanoparticles and their 2D organization by electrophoretic deposition. J. Phys. Chem. B 103, 3818–3827 (1999).
Schill, A. W. & El-Sayed, M. A. Wavelength-dependent hot electron relaxation in PVP capped CdS/HgS/CdS quantum dot quantum well nanocrystals. J. Phys. Chem. B 108, 13619–13625 (2004).
Sun, Y. G., Mayers, B., Herricks, T. & Xia, Y. N. Polyol synthesis of uniform silver nanowires: A plausible growth mechanism and the supporting evidence. Nano Lett. 3, 955–960 (2003).
Variano, B. F. et al. Quantum effects in anisotropic semiconductor clusters - colloidal suspensions of Bi2S3 and Sb2S3 . J. Phys. Chem. 91, 6455–6458 (1987).
Chen, Y., Kou, H. M., Jiang, J. & Su, Y. Morphologies of nanostructured bismuth sulfide prepared by different synthesis routes. Mater. Chem. Phys. 82, 1–4 (2003).
Sigman, M. B. Jr & Korgel, B. A. Solventless synthesis of Bi2S3 (bismuthinite) nanorods, nanowires, and nanofabric. Chem. Mater. 17, 1655–1660 (2005).
Briand, G. G. & Burford, N. Bismuth compounds and preparations with biological or medicinal relevance. Chem. Rev. 99, 2601–2657 (1999).
Acknowledgements
This work was supported in part by the following NIH grants: P50 CA86355, R24 CA92782, UO1 HL080731, U54 CA119349 and RO1-EB004626A01. This work made use of MRSEC Shared Facilities supported by the National Science Foundation under Award Number DMR-0213282 and NSF Laser Facility grant CHE-0111370.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
Supplementary figures S1 and S2 (PDF 106 kb)
Rights and permissions
About this article
Cite this article
Rabin, O., Manuel Perez, J., Grimm, J. et al. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nature Mater 5, 118–122 (2006). https://doi.org/10.1038/nmat1571
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmat1571
This article is cited by
-
Bi-HPDO3A as a novel contrast agent for X-ray computed tomography
Scientific Reports (2023)
-
Hydropathy modulation on Bi2S3 for enhanced electrocatalytic CO2 reduction
Rare Metals (2023)
-
Near-unity broadband luminescent cuprous halide nanoclusters as highly efficient X-ray scintillators
Science China Materials (2023)
-
Gold cluster encapsulated liposomes: theranostic agent with stimulus triggered release capability
Medical Oncology (2023)
-
Next generation lanthanide doped nanoscintillators and photon converters
eLight (2022)