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

Abstract:

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Un F,Zhou B,Yen Y

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

4685-90

issue

11

eissn

0250-7005

issn

1791-7530

pii

32/11/4685

journal_volume

32

pub_type

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