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Xiaoyuan Chen talks with and answers a few questions about this month's Fast Moving Front in the field of Chemistry. The author has also sent along images of their work.
Chen Article: Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects
Authors: Cai, WB;Shin, DW;Chen, K;Gheysens, O;Cao, QZ;Wang, SX;Gambhir, SS;Chen, XY
Journal: NANO LETT, 6 (4): 669-676 APR 2006
Addresses: Stanford Univ, Sch Med, MIPS, 1201 Welch Rd, Stanford, CA 94305 USA.
Stanford Univ, Sch Med, MIPS, Stanford, CA 94305 USA.
Stanford Univ, Sch Med, Bio X Program, Dept Radiol, Stanford, CA 94305 USA.
(addresses have been truncated)

 Why do you think your paper is highly cited?

Weibo Cai

Sanjiv Gambhir

Shan Wang

Even though previous studies have demonstrated the feasibility of using quantum dots for tumor vasculature targeting, this is the first report of imaging of tumor vasculature with quantum dots in a non-invasive manner.

 Does it describe a new discovery, methodology, or synthesis of knowledge?

The conjugation chemistry described in this paper is robust and highly reproducible, which has become essentially the standard method of nanoparticle modification. The study addresses several key issues related to the in vivo application of quantum dots and other nanomaterials, such as particle size, circulation half-life, and reticuloendothelial system (RES) uptake.

 Would you summarize the significance of your paper in layman's terms?

This particular peptide nanoparticle conjugate recognizes the new vessels grown out of a malignant tumor which can be visualized by a specially designed camera. Such kind of molecular imaging technique will have great potential in cancer diagnosis, imaging guided surgical tumor removal, as well as treatment management.

 How did you become involved in this research and were there any particular problems encountered along the way?

Our lab focuses on molecular imaging probe development. We have previously worked with fluorescent dyes for near-infrared fluorescence optical imaging studies. However, fluorescent dyes are not bright enough and photostable enough. Furthermore, fluorescent dyes can produce toxic radicals and photoproducts upon repeated excitation. It is also rather difficult to multiplex several colors. Quantum dots, on the other hand, have size-tunable narrow emission spectra, ideally suited for in vivo imaging application, but were not previously well studied.

 Where do you see your research leading in the future?

In this particular study we used quantum dots from commercial sources. These materials contain toxic heavy metals such as cadmium. We are now trying to develop alternatives to cadmium chalcogenide nanocrystal emitters. Other than RGD peptides, we are also testing other targeting molecules including antibodies, proteins, and peptides.

Figure 1:  
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We are also studying the effect of particle size, rigidity, and surface chemistry on the targetability and cellular distribution of the newly developed biocompatible quantum dot conjugates. We are hopeful that our nanobiotechnology will be clinically relevant and translated into clinical use in the foreseeable future.

 Do you foresee any social or political implications for your research?

Nanotechnology plays an essential role in molecular imaging and future molecular medicine. Despite the great promise of nanomedicine, there are still major hurdles such as biocompatibility, pharmacokinetics, targeting efficiency, cost-effectiveness, and acute/chronic toxicity, most of which are virtually untouched. This paper, along with our other related publications, will likely gain a lot more interest from the scientific and medical community, helping to push the field of nanomedicine forward.

Xiaoyuan (Shawn) Chen, Ph.D.
Molecular Imaging Program at Stanford (MIPS)
Department of Radiology, Bio-X & Biophysics
Stanford University School of Medicine
Stanford, CA, USA

Figure 1:

Figure 1:

RGD peptide-conjugated QD705 for NIRF imaging of tumor vasculature. a) A schematic illustration of the probe QD705-RGD. b) An atomic force microscopy image of QD705-RGD deposited on a silicon wafer. c) In vivo NIRF imaging of tumor vasculature in U87MG human glioblastoma tumor-bearing mice. The mouse on the left was injected with QD705-RGD and the mouse on the right was injected with QD705. Arrows indicate tumors.

Keywords: quantum dots, tumor vasculature targeting, conjugation chemistry, peptide nanoparticle conjugate, molecular imaging probe development, alternatives to cadmium chalcogenide nanocrystal emitters, newly developed biocompatible quantum dot conjugates, nanobiotechnology, molecular imaging, molecular medicine, nanomedicine.

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2008 : November 2008 - Fast Moving Fronts : Xiaoyuan Chen