The utility of tumor-specifically internalizing peptides for targeted siRNA delivery into human solid tumors.
Anticancer Res
; 32(11): 4685-90, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-23155230
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 ANDMETHODS:
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.
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Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Neoplasias da Mama
/
Terapia Genética
/
Sistemas de Liberação de Medicamentos
/
RNA Interferente Pequeno
/
Neoplasias de Cabeça e Pescoço
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article