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The utility of tumor-specifically internalizing peptides for targeted siRNA delivery into human solid tumors.

BACKGROUND
Ribonucleotide reductase composed of the hRRM1 and hRRM2 subunits catalyzes the conversion of ribonucleotides to their corresponding deoxy forms for DNA replication. Anti-hRRM2 siRNA degrades hRRM2's mRNA and suppresses tumorigenesis. A Phase I clinical trial demonstrated its therapy potential. HN-1 represents a tumor-specifically internalizing peptide for targeted-drug delivery into human head and neck squamous cell carcinoma.


MATERIALS AND METHODS
Internalization of peptide was monitored by fluorescence microscopy. The peptide-siRNA conjugate was chemically synthesized. The hRRM2 expression was monitored by western blot analysis.


RESULTS
HN-1(TYR) (HN-1 with two N-terminally added tyrosines) was internalized by human head and neck or breast cancer cells. Anti-hRRM2 siRNA(R) (resistant to RNase degradation) was conjugated to HN-1(TYR) without compromising their properties. The treatment with HN-1(TYR)-anti-hRRM2 siRNA(R) partly suppressed the endogenously expressed hRRM2 in human breast cancer cells.


CONCLUSION
Our results establish the utility of tumor-specifically internalizing peptides for targeted siRNA delivery into human cancer cells.