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

Frank Un, Bingsen Zhou, Yun Yen

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 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-1TYR (HN-1 with two N-terminally added tyrosines) was internalized by human head and neck or breast cancer cells. Anti-hRRM2 siRNAR (resistant to RNase degradation) was conjugated to HN-1TYR without compromising their properties. The treatment with HN-1TYR-anti-hRRM2 siRNAR 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.

Original languageEnglish
Pages (from-to)4685-4690
Number of pages6
JournalAnticancer Research
Volume32
Issue number11
Publication statusPublished - Nov 1 2012
Externally publishedYes

Fingerprint

Small Interfering RNA
Peptides
Neoplasms
Breast Neoplasms
Ribonucleotides
Ribonucleotide Reductases
Clinical Trials, Phase I
Ribonucleases
Head and Neck Neoplasms
DNA Replication
Fluorescence Microscopy
Tyrosine
Carcinogenesis
Western Blotting
Messenger RNA
Pharmaceutical Preparations
Therapeutics

Keywords

  • Cancer
  • Delivery
  • hRRM1
  • hRRM2
  • Peptide
  • siRNA
  • Tumor-specifically internalizing peptide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The utility of tumor-specifically internalizing peptides for targeted siRNA delivery into human solid tumors. / Un, Frank; Zhou, Bingsen; Yen, Yun.

In: Anticancer Research, Vol. 32, No. 11, 01.11.2012, p. 4685-4690.

Research output: Contribution to journalArticle

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AB - 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-1TYR (HN-1 with two N-terminally added tyrosines) was internalized by human head and neck or breast cancer cells. Anti-hRRM2 siRNAR (resistant to RNase degradation) was conjugated to HN-1TYR without compromising their properties. The treatment with HN-1TYR-anti-hRRM2 siRNAR 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.

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