Dong Shin, MD, of Emory University and Mark Davis, PhD, of the Nanosystems Biology Cancer Center at the California Institute of Technology had previously developed a nanoparticle that encapsulates a siRNA agent aimed at a protein known as RRM2. For this study they again collaborated to evaluate the effectiveness of these particles in head and neck cancer (JCR February 8, 2012).
RRM2, when overexpressed in these tumor types, plays an active role in tumor progression and in the development of drug resistance, the researchers noted. Initial tests on head and neck tumor cells growing in culture showed that this construct was taken up by the tumor cells, and as a result growth of the cells was inhibited substantially.
Based on these findings, the researchers tested a siRNA-loaded nanoparticle in a mouse model of human head and neck cancer. One intravenous injection of the drug shut down production of RRM2 for at least 10 days, with the nanoparticle being present in the tumor for three days, they reported. Four injections given over 10 days triggered a substantial amount of tumor cell death and significantly reduced tumor progression.
The researchers did not observe any adverse effects or changes in body weight during therapy. In addition, the drug had no effect on RRM2 production in the liver.
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