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 tumorspecifically 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.