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.
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ACKNOWLEDGMENTS
This work was supported by awards from National Cancer Institute (NCI), NIH (1R21CA143683-01) and National Institute of Alcohol Abuse and Alcoholism (NIAAA), NIH (1R21AA017960-01A1). We also would like to express thanks for the financial support from a start-up package at the University of Missouri-Kansas City.
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Qin, B., Tai, W., Shukla, R.S. et al. Identification of a LNCaP-Specific Binding Peptide Using Phage Display. Pharm Res 28, 2422–2434 (2011). https://doi.org/10.1007/s11095-011-0469-7
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DOI: https://doi.org/10.1007/s11095-011-0469-7