title: A novel truncated basic fibroblast growth factor fragment-conjugated poly (ethylene glycol)-cholesterol amphiphilic polymeric drug delivery system for targeting to the FGFR-overexpressing tumor cells.
abstract: Targeted uptake of therapeutic nanoparticles in tumor cells-specific manner represents a potentially powerful technology in cancer therapy. In present study, we proposed a drug delivery system formulated with biocompatible and biodegradable cholesterol-block-poly (ethylene glycol) (Chol-PEG(2000)-COOH) polymer. And the surface of the polymer was chemically linked with truncated bFGF fragments (tbFGF). The tbFGF could recognize fibroblast growth factor receptors (FGFR) that are highly expressed by a variety of human cancer cells. The micelles had a size distribution of about 10-50 nm and significantly enhanced the cytotoxicity of paclitaxel to LL/2 cells as demonstrated by MTT test (IC₅₀=0.21 μg/mL for tbFGF conjugated Chol-PEG(2000)-COOH micelles (tbFGF-M-PTX) versus 26.43 μg/mL for free paclitaxel, respectively). Flow cytometry revealed the cellular uptake of rhodamine B encapsulated in the tbFGF-conjugated micelles was increased by 6.6-fold for HepG2, 6.2-fold for A549, 2.9-fold for C26 and 2.7-fold for LL/2 tumor cells, respectively, compared with micelles without tbFGF. The fluorescence spectroscopy images further demonstrated that the tbFGF conjugated micelles could specifically bind to the tumor cells that over-expressed FGFRs and then release rhodamine B into the cytoplasm. Our results suggest the tbFGF conjugated Chol-PEG(2000)-COOH micelles have great potential application for tumor targeting therapy.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Kaili
authors.initials: K
authors.lastname: Luo
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D008823:Micelles; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D010316:Particle Size; D010446:Peptide Fragments / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010446:Peptide Fragments; D017468:Receptors, Fibroblast Growth Factor; D013501:Surface-Active Agents; C118255:polyethylene glycol-cholesterol; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D002784:Cholesterol