In vivo imaging of siRNA delivery and silencing in tumors

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Using magnetic nanoparticles labeled with dye molecules, a team of investigators at the Massachusetts General Hospital has developed a delivery vehicle capable of transporting antitumor small interfering RNA (siRNA) molecules into cells.

Moreover, this multifunctional nanoparticle can then be used to confirm that delivery took place using either magnetic resonance imaging (MRI) or fluorescence optical imaging (FOI). Anna Moore, Ph.D., led the research team, which published its results in the journal Nature Medicine.

Delivering siRNA molecules into tumors has proved difficult, although several research teams have found that nanoparticles may be the ideal delivery vehicle for these cancer gene-silencing agents. In this work, Moore and her colleagues used coated iron oxide nanoparticles as the foundation for creating their multifunctional nanoscale drug delivery and imaging device. First, the investigators attached an average of three dye molecules to the iron oxide nanoparticles. Next, they added an average of four membrane-penetrating molecules known as myristoylated polyarginine peptide (MPAP) to the nanoparticle surface. Finally, the researchers linked an average of five siRNA molecules to their multifunctional core.

After injecting this construct into tumor-bearing mice, the investigators were able to track its uptake by the tumors using both MRI, which detects the magnetic iron oxide core, and FOI, which detects the fluorescent molecules attached to the nanoparticle surface. These experiments demonstrated that large numbers of the nanoparticles accumulated in tumors. The investigators were also able to use fluorescence microscopy to show that the siRNA agent was both taken up along with the nanoparticles and able to silence a known cancer gene in the tumors.

This work is detailed in the paper "In vivo imaging of siRNA delivery and silencing in tumors." An abstract of this paper is available through PubMed. View abstract.


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