A novel peptide specifically binding to nasopharyngeal carcinoma for targeted drug delivery.
Nasopharyngeal carcinoma (NPC) is a common cancer among Chinese living in southern China, Taiwan, and Singapore. The 5-year survival rate in the early stage of NPC has been reported as high as 90 to 95% with the use of radiotherapy, but in the advanced cases, even with the use of both chemotherapy and radiotherapy, the survival rate is still <50%. To improve the survival rate, we identify a 12-mer peptide (L-peptide) specifically binding to NPC cells with a phage displayed random peptide library. The L-phage and synthetic L-peptide bound to the tumor cell surfaces of most NPC cell lines and biopsy specimens, but not normal nasal mucosal cells, and the L-peptide-linked liposomes containing fluorescent substance (L-peptide-Lipo-HPTS) were capable of binding to and translocating across plasma membranes. L-Peptide-linked liposomes that carried doxorubicin (L-peptide-Lipo-Dox) caused marked cytotoxicity in NPC cells. In SCID mice bearing NPC xenografts, the L-phages specifically bound to the tumor mass, an effect that was inhibited by competition with synthetic L-peptide. In addition, the L-peptide-Lipo-Dox suppressed tumor growth better than Lipo-Dox. These results indicate that the novel L-peptide specifically binds NPC cells and is a good candidate for targeted drug delivery to NPC solid tumors.
Lee
Tong-Young
TY
Institute of Pathology and Graduate Institute of Oral Biology, College of Medicine, National Taiwan University, Taipei.
Wu
Han-Chung
HC
Tseng
Yun-Long
YL
Lin
Chin-Tarng
CT
D000818:Animals; D001665:Binding Sites; D004317:Doxorubicin / Q000008:administration & dosage*; D004705:Endocytosis; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D014183:Transplantation, Heterologous
D008081:Liposomes; D019151:Peptide Library; D010455:Peptides; D004317:Doxorubicin