title: Basic fibroblast growth factor-binding peptide as a novel targeting ligand of drug carrier to tumor cells.
abstract: Drug systems targeting tumor cells using basic fibroblast growth factor (bFGF) have been widely reported. In this study, the peptide KRTGQYKLC (bFGFp), containing cysteine at the carboxyl termination of the bFGF-derived peptide, was applied as a novel ligand targeting tumor cells. bFGFp was conjugated with bovine serum albumin (BSA) and liposomes. The peptide was shown to inhibit the binding of bFGF to FGF receptor-1 (FGFR1). Interestingly, the binding study using surface plasmon resonance (SPR) assay revealed that the bFGFp-BSA was not bound to FGFR1, but was selectively bound to bFGF. Furthermore, the SPR assay showed that bFGFp-BSA is capable of binding to FGFR1 following the pretreatment with bFGF. The confocal microscopy study indicated that the uptake of bFGFp-BSA by NIH3T3 cells, which highly express FGFRs, was significantly enhanced by pretreatment with bFGF. Then, PEGylated liposomes containing bFGFp (bFGFp-liposome) were prepared by conjugating maleimide-PEG-PE with bFGFp. Following the pretreatment of bFGF, the uptake of bFGFp-liposomes by NIH3T3 cells was significantly enhanced. These results suggest that bFGFp-BSA and bFGFp-liposomes are taken by NIH3T3 cells via binding with bFGF. In addition, both bFGFp-BSA and bFGFp-liposomes had no effect on the proliferation of NIH3T3 cells. This strategy can be used as a novel system for targeting tumors highly expressing FGFRs without a proliferation effect.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terada
authors.forename: Miki
authors.initials: M
authors.lastname: Mizobata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yabe
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004337:Drug Carriers / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D008024:Ligands; D008081:Liposomes; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011485:Protein Binding; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D020349:Surface Plasmon Resonance
chemical_list: D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; D016222:Fibroblast Growth Factor 2; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D051496:Receptor, Fibroblast Growth Factor, Type 1