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Selective targeting of drugs to tumor cells is a key goal in oncology. Here, we performed an in vivo phage display to identify peptides that specifically target xenografted prostate cancer cells. This yielded three peptide candidates, LN1 (C-TGTPARQ-C), LN2 (C-KNSMFAT-C), and LN3 (C-TNKHSPK-C); each of these peptides was synthesized and evaluated for binding and biological activity. LN1 showed the highest avidity for LNCaP prostate cancer cells in vitro and was thus administered to tumor-bearing mice to evaluate in vivo binding. Strikingly, LN1 specifically bound to the tumor tissue and exhibited very low reactivity with normal liver and kidney tissues. To demonstrate that LN1 could specifically deliver drugs to prostate cancer tissue, a therapeutic peptide, LN1-KLA (C-TGTPARQ-C-GGG- D [KLAKLAK] 2 ), was prepared and used to treat LNCaP cells in vitro and was also administered to tumor-bearing mice. The therapeutic peptide significantly suppressed growth of the cells both  in vitro and in vivo . Our study shows that a selective homing peptide strategy could facilitate cell-specific targeting of therapeutics while avoiding adverse reactions in normal tissues.

Efficient Prostate Cancer Therapy with Tissue-Specific Homing Peptides Identified by Advanced Phage Display Technology