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Micelle “packets” deliver cancer drugs

Apr. 8, 2015, 8:00 AM

by Barbara O’Brien

Small interfering RNA (siRNA) molecules can suppress tumor growth and target cells otherwise untreatable by conventional therapeutics, but targeted, intracellular delivery is a significant limitation to siRNA translation.

To deliver the siRNA molecules into tumor cells, researchers have packaged them in micelles that express folic acid, which is internalized by cancer cells that overexpress folate receptors. A problem with this approach is that normal healthy tissue can also have a high expression of folate receptors, resulting in off-target effects.

To increase specificity, Craig Duvall, Ph.D., Todd Giorgio, Ph.D., and colleagues utilized an additional hallmark of breast cancer – elevated matrix metalloproteinase (MMP) – to create mixed micelles that have an outer layer of matrix metalloproteinase-7 (MMP7) cleavable peptide. Thus, only in an MMP-rich environment will the MMP7 be cleaved to expose the folic acid and deliver the therapeutic siRNA.

In a study published recently in Biomacromolecules, the researchers show that their new design has better target specificity and protein expression knockdown in breast cancer cells.

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