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Review
. 2010 Dec;16(12):561-73.
doi: 10.1016/j.molmed.2010.09.004. Epub 2010 Nov 10.

Inorganic nanoparticle-based contrast agents for molecular imaging

Eun Chul Cho  1 , Charles Glaus, Jingyi Chen, Michael J Welch, Younan Xia
Affiliations
Review

Inorganic nanoparticle-based contrast agents for molecular imaging

Eun Chul Cho et al. Trends Mol Med. 2010 Dec.

Abstract

Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imaging, and also touch on contrast enhancement, surface modification, tissue targeting, clearance and toxicity. As research efforts intensify, contrast agents based on inorganic NPs that are highly sensitive, target-specific and safe to use are expected to enter clinical applications in the near future.

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Figures

Figure 1
Figure 1
Typical examples of in vivo molecular imaging with inorganic NPs as contrast agents that are often modified with ligands to target tumors or other diseased lesions. (a) MR imaging of lymph nodes with iron oxide NPs for detecting the metastasis of prostate cancer. (Reproduced with the permission of [24].) (b) MR imaging with antibody-conjugated superparamagnetic iron oxide NPs for tumor targeting. (Reproduced with the permission of [25].) (c) X-ray CT of a mouse bearing tumors (indicated by arrows) as enhanced by PEGylated gold nanorods. (Reproduced with the permission of [31].) (d) Optical fluorescence imaging for detecting human prostate cancer with targeted QDs. (Reproduced with the permission of [21].) (e) Photoacoustic imaging with targeted gold nanocages for detecting human melanoma in a nude mouse. Reproduced with the permission of [27]. (f) SERS spectra with targeted gold NPs for detecting a human squamous cell carcinoma. (Reproduced with the permission of [15].)
Figure 2
Figure 2
Strategies for the bioconjugation of targeting ligands to the surfaces of inorganic NPs. (a) QDs and (b) magnetic NPs are typically hydrophobic or easy to aggregate owing to their magnetic properties, but surface coating is an essential step to ensure their stability and facilitate their conjugation with targeting ligands. Surface coating can be generally achieved using amphiphilic molecules or inorganic materials (e.g. silica), and the targeting ligands can then be added through coupling reactions. (c) The bioconjugation of gold NPs with targeting ligands is easier than the other two types of NPs owing to their ability to form gold–thiolate bonding. As such, the target ligands can be directly coupled to the surfaces of Au NPs or conjugated to the surface of an organic layer (e.g. PEG) that is chemically grafted to the Au surface. (d) Typical chemical reactions involved in coupling the targeting ligands to the NPs. In general, one can use the primary amine in a protein or peptide to react with succinimidyl esters or carboxylic acid with the aid of EDC. Alternatively, if the targeting ligands have thiol groups they can be attached to the NPs via the maleimide–thiol reaction.
Figure 3
Figure 3
The delivery of inorganic NPs to the site of interest. (a) A schematic showing the enhanced permeation and retention effect in selectively delivering NPs to a tumor site. In contrast to normal tissue, the vasculature in a tumor is leaky and the cancer cells are less densely packed owing to their tendencies to grow fast. This allows NPs to enter the tumor tissue more easily than they can the normal tissue. This effect is also known as “passive targeting.” (b) The comparison of delivery with targeted NPs for active targeting with nontargeted (typically PEGylated) NPs for passive targeting. When the surfaces of NPs are modified with PEG, the NPs are hardly taken up by cells owing to the antifouling property of PEG. By comparison, NPs modified with target ligands can bind to the receptors on the surfaces of cells and thereby facilitate the internalization of NPs by cells. (c) When NPs are used to detect a disease other than cancer, NPs bearing target ligands can preferentially bind to the diseased site relative to the nontargeted NPs, and thereby the targeted NPs will provide better contrast enhancement.
Figure 4
Figure 4
The biodistributions of inorganic NPs after intravenous injections into mice. (a) The biodistributions of QDs with two different sizes. (The figure was replotted with the permission of [105].) (b) The biodistribution of QDs covered with different functional groups. (The figure was replotted with the permission of [109].) (c) The amount of dextran-coated iron oxide NPs accumulated in the liver as a function of their sizes. (d) The biodistribution of iron oxide NPs with different surface charges. (e) The amount of iron oxide NPs accumulated in the liver when their surfaces were coated with different functional groups. (The figures in (c–e) were replotted with the permission of [57].) (f) The biodistributions of Au colloids with different geometries. The dimensions of the Au nanospheres, nanorods and nanocages are labeled as diameter, width × length and outer edge length, respectively. (The figure was replotted with the permission of [–108].)
Figure 5
Figure 5
Inorganic NPs as contrast agents for multimodal imaging. (a) Top: schematic showing iron oxide (IO) NPs conjugated with DOTA and RGD for MR imaging and PET. Bottom: MR (left) and PET images (right) after the intravenous injection of the IO-DOTA-RGD. Arrows indicate the tumors in nude mice. (Reproduced with the permission of [119].) (b) Top: schematic showing a QD conjugated with DOTA and RGD for PET and fluorescence imaging. Bottom: PET and fluorescence images after the intravenous injection of the DOTA-QD-RGD NPs. Arrows indicate the tumors in nude mice and the fluorescence image was taken from the circled region in the PET image. (Reproduced with the permission of [120].)
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References

    1. Weissleder R, Mahmood U. Molecular imaging. Radiology. 2001;219:316–333. - PubMed
    1. Achilefu S. Introduction to concept and strategies for molecular imaging. Chem. Rev. 2010;110:2575–2578. - PubMed
    1. Licha K. Contrast agents for optical imaging. Topics Curr. Chem. 2002;222:1–29.
    1. Gao X, et al. In vivo molecular and cellular imaging with quantum dots. Curr. Opin. Biotechnol. 2005;16:63–72. - PubMed
    1. Erdi YM. The use of PET for radiotherapy. Curr. Medical Imaging Rev. 2007;3:3–16.

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