Identification of a LNCaP-specific binding peptide using phage display

Pharm Res. 2011 Oct;28(10):2422-34. doi: 10.1007/s11095-011-0469-7. Epub 2011 May 25.

Abstract

Purpose: To identify a LNCaP-specific peptide using a phage display library and evaluate its potential applications in targeted drug delivery.

Methods: Binding abilities of selected phages were evaluated by cell phage ELISA. The KYL peptide encoded by the most specific phage clone was synthesized, labeled with fluorescein, and assayed in various cell lines. A fusion peptide composed of the KYL peptide and a proapoptotic peptide ( D )(KLAKLAK)(2) was synthesized, and the cell death effect was evaluated on different cells. Moreover, the KYL peptide was conjugated to a cationic protein, protamine, to explore its potential application in siRNA delivery.

Results: One phage clone with a high binding affinity to LNCaP cells was identified. Cell phage ELISA and immunostaining demonstrated high specificity of this phage to LNCaP cells. The fluorescein-labeled KYL peptide exhibited higher binding to LNCaP cells in comparison to other cells. The fusion peptide composed of the KYL peptide and the proapoptotic peptide induced cell death in LNCaP cells, but not in PC-3 cells. The KYL peptide-protamine conjugate also efficiently delivered a fluorescein-labeled siRNA into LNCaP cells.

Conclusion: We identified a LNCaP-specific peptide and demonstrated its potential applications in targeted drug delivery to LNCaP cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteriophages / genetics
  • Bacteriophages / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Male
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / pharmacology
  • Peptide Library*
  • Peptides / genetics*
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / metabolism*
  • Protamines / metabolism
  • Protein Binding
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Rats

Substances

  • Neoplasm Proteins
  • Peptide Library
  • Peptides
  • Protamines
  • RNA, Small Interfering