title: Optimization of tumor-selective targeting by basic fibroblast growth factor-binding peptide grafted PEGylated liposomes.
abstract: We have previously shown that the peptide, KRTGQYKLC (bFGF), is recognized by fibroblast growth factor (FGF) receptor (FGFR) via binding to basic FGF (bFGF), and is capable of being used for drug delivery to tumors highly expressing FGFR and bFGF. However, although the binding and uptake of the liposomes (bFGFp-liposomes) modified by the peptide increased in the presence of bFGF, the modification induced non-specific uptake. To overcome this problem, here, we prepared bFGFp-liposomes including mPEG-DSPE. The 5 and 10% mPEG(5000)/ and 10% mPEG(3000)/bFGFp-liposomes reduced most of the interaction with erythrocytes and the uptake by macrophages, suggesting the sustained blood circulation of bFGFp grafted PEGylated liposomes. Furthermore, 10% mPEG(3000)/bFGFp-liposomes produced a significant increase in uptake in NIH3T3, A549, and B16BL6 cells with the expression of FGFR following pre-incubation with bFGF, but no increase in CHO-K1 cells lacking FGFR expression. Taken together, these results lead us to believe that bFGFp grafted PEGylated liposomes possess the functions of both PEGylated stealth liposomes and the tumor-targeting liposomes. This strategy could be applied to the development of novel tumor-selective drug delivery systems.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 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: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004912:Erythrocytes / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D005347:Fibroblasts; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1