title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Our results establish the utility of tumor-specifically internalizing peptides for targeted siRNA delivery into human cancer cells.
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Un
authors.forename: Bingsen
authors.initials: B
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
chemical_list: C417565:HN-1 peptide; D009842:Oligopeptides; D034741:RNA, Small Interfering; D012264:Ribonucleotide Reductases