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9/3/2007 9:15:34 PM
Targeting Quantum Dots To Deliver SiRNA Therapy

Take a quantum dot, add a coating of poly(ethylene glycol) (PEG), and attach a homing peptide and a piece of small interfering RNA (siRNA), and the result is a targeted nanoparticle that can stop the production of a specific protein by a targeted cell. If the homing peptide targets tumor cells and the siRNA molecule shuts down a cancer-related protein, the result could be a new type of anticancer agent that would also double as an imaging agent.

Reporting its work in the journal Bioconjugate Chemistry, a team of investigators led by Sangeeta Bhatia, M.D., Ph.D., of the Massachusetts Institute of Technology, and Erkki Ruoslahti, M.D., Ph.D., of the Burnham Institute for Medical Research, both members of the NCI Alliance for Nanotechnology in Cancer, described its work developing the new imaging and siRNA delivery platform. Their studies included experiments designed to optimize the relative amounts of homing peptide and siRNA attached to the coated quantum dot.

As the foundation for their new platform, the investigators chose a commercially available, PEG-coated quantum dot that emits light in the near-infrared range, a region of the optical spectrum that passes easily through skin and other tissues. The PEG coating renders the quantum dots biocompatible and provides an attachment site for the homing peptide and siRNA. However, the small size of the quantum dot and the chemical makeup of PEG result in only about 100 total attachment sites for both the homing peptide and siRNA molecule. In addition, the investigators explored two types of linkers for attaching siRNA molecules—one permanent but flexible, the other capable of releasing free siRNA once the nanoparticle is taken into the targeted cell.

After conducting exhaustive studies of particle uptake and siRNA release, the investigators determined that a ratio of 20 homing peptides to 1 siRNA molecule produced the optimal level of protein suppression. These studies also demonstrated the superiority of using a cleavable linkage for attaching the siRNA molecule.

This work, which was supported by the NCI’s Alliance for Nanotechnology in Cancer, is detailed in the paper “Targeted quantum dot conjugates for siRNA delivery.” Investigators from the University of California, San Diego, and Harvard University also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.

View abstract.

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