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Nasopharyngeal carcinoma (NPC) is one of the most common cancers among Chinese living in South China, Taiwan and Singapore. For treatment of NPC, although radiotherapy, surgical removal, and chemotherapy have been applied for decades and the 5 year survival rate in the advanced cases are still below 75 %. Much effort using other methods such as high dose chemotherapy plus bone marrow stem cell injection and other targeting therapy are needed to control this cancer. In the present experiment, we used random peptide phage display libraries to identify and isolate a specific novel peptide from NPC cell line for targeting drug delivery. After subtraction with control epithelial cells for 3 times, the remained phage libraries were biopanning on NPC-TW04 cells for 5 rounds. It was found that 44 selected phage clones could specifically bind to NPC cell surface. When ELISA was used to verify those clones, 16 phage clones showed higher affinity to NPC cells and were subjected to DNA sequencing. The alignment of phage displayed peptide sequences revealed two amino acid residues having a consensus sequence in five phage clones and two of the phage clones showed a consensus sequence involving three amine acid residues. We selected one of phage clones labeled as L-phage for further characterization. After extensive characterization including modified immunohistochemical localization with competitive control both in vitro and in vivo, the L-phage peptide sequence was synthesized (L-peptide). This L-peptide also revealed specific binding to NPC cell surfaces. We then linked this specific peptide with a liposome containing anti-cancer drugs for targeting NPC cell surface both in vitro and in vivo. In vitro, the peptide bound to the cell surfaces of the majority of NPC cell lines and biopsy specimens; the peptide-linked fluorescence containing liposome was capable of binding to and translocation across plasma membranes. Similarly, the peptide-linked liposome that carried doxorubicin (L-peptide-Lipo-Dox) could cause marked NPC cytotoxicity. In vivo, in SCID mice bearing NPC xenograft, the L-peptide-Lipo-Dox had higher efficacy to inhibit tumor growth than Lipo-Dox. These results indicate that the L-peptide is a novel peptide, which can specifically bind to NPC cells, and is a good candidate for targeted drug delivery to NPC solid tumors.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]