Gadolinium Chelate Coated Gold Nanoparticles

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Introduction

The objective of investigations in oncology is the discovery and assessment of therapeutic strategies on models. These studies require efficient and modern functionalized contrast agents to envisage tumor growth, for evaluating the effect of treatment, and/or for propagating the annihilation of cancerous tumors. These applications involve ample pharmacokinetic aspects and minimal levels of nonspecific accumulation in the body (Alric, Taleb and Le Duc 5909).

Advantages of Developing Nanoparticles as Contrast Agents for Medical Imaging

Previously documented research has focused on the development of nanoparticles as contrast agents for medical imaging. This is because their vascular half-life is longer than molecular contrast agents. Consequently, the particulate contrast agents can be examined for a longer duration after the delivery to a living organism. When a clinical diagnosis requires the rapid elimination of the contrast, then their presence for a longer time is necessary for examining the biodistribution of drugs or radiosensitizing agents for cancer treatment and the response to therapy in animal models (Alric, Taleb and Le Duc 5910).

The nanoparticles are also advantageous over molecular contrast agents due to their capability to assemble in the same object, many complementary properties. It is because of this attribute that the development of multifunctional nanoparticles, which can be detected by several in vivo imaging techniques, was developed. The most commonly studied possibilities are the nanoparticles combining fluorescent imaging and magnetic resonance imaging (MRI). This can be tied to their ability to ally the high sensitivity of the fluorescence phenomenon to the high spatial resolution of MRI (Alric, Taleb and Le Duc 5910).

Techniques in Diagnostic Clinical Medicine

MRI has, over the years, become a major non-invasive technique in diagnostic clinical medicine. This is due to the likelihood of getting highly resolved three-dimensional images of living bodies. One of the limitations of MRI is that the in vivo application of the fluorescent MRI contrast agents is restricted to small animal imaging due to the autofluorescence, the strong light absorption, and scattering, which limit the spatial resolution (Lewinski, Colvin and Drezek 29).

Contrast Agents for Computed Tomography (CT)

The extensive use for X-ray computed tomography (CT) imaging diagnosis is because of the ability for X-rays to go across the human body. It is therefore, possible to visualize internal anatomic structures externally, without surgery; however, it may be necessary to administer contrast agents. The daily application of Iodinated molecules as contrast agents for CT imaging is necessary due to the high X-ray absorption coefficient of iodine and their innocuousness (except in a few cases of patients with poor kidney function), but their rapid pharmacokinetics and the high viscosity of the injectable solution can however, constitute a handicap (Lewinski, Colvin and Drezek 33).

CT has a ubiquitous nature in clinical settings, though the development of nanoparticles as contrast agents for CT got minimal notice, though they can provoke superior contrast enhancement of CT images than iodinated compounds.

In addition to this, the nanoparticles are renowned for their multifunctionality, which is the main benefit over conventional methods, since it allows merging of a variety of imaging techniques or imaging and therapy (Lewinski, Colvin and Drezek 33).

The use of dense nanoparticles, which bear high atomic number elements as contrast agents for X-ray CT imaging, was a newly introduced concept. Gold nanoparticles were efficiently applied in vivo as X-ray contrast agents. It was expected that these particles induce, for the same content of absorbing element, higher contrast than iodinated compounds; an ability that was observed to be independent of the diameter of gold nanoparticles since similar contrast enhancement is observed for both 1.9 and 31 nm sized particles (Lewinski, Colvin and Drezek 34).

Gold nanoparticles are more attractive candidates since it is easier to control their size, shape, and surface chemical composition. The facile derivatization of gold nanoparticles is central to developing new tools for biomedical application, which meet the criteria of clinical use. Gold nanoparticles functionalized by gadolinium chelates are able to induce in vitro positive contrast in the MR images; this makes the particles very attractive since they can behave as contrast agents for both X-ray imaging and MRI (Lewinski, Colvin and Drezek 35).

Experiment

This paper looks at the results of the in vivo application of gadolinium chelate coated gold nanoparticles, after intravenous injection to mice and rats. The biodistribution of the nanoparticles was monitored by MRI (at 7T) and X-ray imaging, which was performed at the biomedical beamline of the European Synchrotron Radiation Facility (ESRF). This biomedical line affords attractive conditions for computed tomography (SRCT for Synchrotron Radiation Computed Tomography) because synchrotron radiation provides monochromatic X-ray beams whose intensity is 5 orders of magnitude higher than the one provided by conventional X-ray sources (Krause and Schneider 112).

Conventional scanners are not ideal since their performance is limited by intensity variations, limited flux and broad energy spectrum. SRCT is, on the other hand, ideal since they allow quantifying the contrast agent concentration in the tissues. The non-destructive and absolute quantitative in vivo measurement of gold concentration constitutes an original and attractive feature of monochromatic X-ray beams for monitoring in real-time, the bio-distribution of gold nanoparticles since it does not require the sacrifice of the animal in contrast to the post-mortem ICP analyses (Krause and Schneider 113).

Conclusion

X-ray imaging and MRI experiments coupled to ICP analysis show that Au@DTDTPA-Gd nanoparticles can be applied as in vivo contrast agents for both imaging techniques, which are the most widely used for preclinical research. Despite the low content in gold (10 mg·mL-1) and in gadolinium (5 mM), the particles were easily detected. Their ability to liberally flow in the blood pool with no detrimental build-up in the lungs, liver, and spleen, along with the fact that they can be followed up by either MRI or X-ray imaging, is very attractive for specific targeting (Rabin, Perez and Grimm 119).

This is because the accumulation would result only from the specific interaction between the bio targeting groups on the particles and the targets present in the zone of interest. Specific targeting, which is required for the early detection of cancer and its treatment can be achieved by the covalent grafting of bio targeting groups on the organic multilayer of the Au@ DTDTPA-Gd nanoparticles since each DTDTPA ligand possesses three COOH moieties as anchoring sites.

Since gold nanostructures can induce the destruction of cancerous cells after activation with an external physical stimulus (electromagnetic radiation in X-ray and near-infrared spectral domains), the development of nanoparticles for targeted diagnosis and therapy can, therefore, be envisaged with Au@DTDTPA-Gd nanoparticles (Rabin, Perez and Grimm 120).

Works Cited

Alric, Christophe, et al. Gadolinium Chelate Coated Gold Nanoparticles As Contrast Agents for Both X-ray Computed Tomography and Magnetic Resonance Imaging. J. Am. Chem. Soc. 9 (2008): 130(18), 5908-5914.

Krause, Werner and Peter Schneider. Chemistry of X-ray Contrast Agents. Journal of the American Chemical Society (2002): 222, 107-150.

Lewinski, N., V Colvin and R. Drezek. Cytotoxicity of nanoparticles. Small (2008): 4(1), 26-49.

Rabin, Oded, et al. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nature Materials (2006): 5, 118-122.

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