Targeted Nanogels Specifically Transport siRNA into Ovarian Cancer Cells

Nanoparticles crafted from hydrogels (nanogels) have been coated with receptor-specific peptides and used to transport siRNA (small, interfering RNA) capable of inhibiting the synthesis of epidermal growth factor receptor (EGFR) into ovarian cancer cells.

Targeted cancer therapy by RNA interference is a relatively new approach that can be used to silence reversibly genes in vivo. In this study, RNA interference technology was used to shut down the gene for EGFR in ovarian cancer cells. Removal of this gene had been shown previously to increase the sensitivity of cancer cells to chemotherapeutic agents.

Delivery of the nucleic acid fragment has been the main hurdle delaying the broad development of siRNA-based therapeutics. In the current study, investigators at the Georgia Institute of Technology (Atlanta, USA) have gotten around this problem by protecting siRNA particles by enclosing them within hydrogel nanoparticles (nanogels). The siRNA was specific for the gene that encodes EGFR, which is highly overexpressed in some types of ovarian cancer. To ensure that the nanogels targeted only cancer cells, they were coated with peptides specific for the EphA2 receptor. Once bound to EphA2 receptors within the cancer cells the particles slowly released the siRNA over a timescale of days, allowing it to have a therapeutic effect.

Results published in the January 11, 2010, online edition of the journal BMC Cancer revealed that treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel. Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity.

"With our technique we are inhibiting EGFR's growth, with small interfering RNA. And by inhibiting its growth, we are increasing the cell's apoptotic function. If we hit the cell with chemotherapy at the same time, we should be able to kill the cancer cells more effectively,” said senior author Dr. John McDonald, professor of biology at the Georgia Institute of Technology. "The fact that this system is releasing the siRNA slowly, without giving the cell time to immediately recover, gives us much better efficiency at killing the cancer cells with chemotherapy.”

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Georgia Institute of Technology