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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-6-1
pubmed:abstractText
Fibroblast growth factor receptors (FGFRs), overexpressed on the surface of a variety of tumor cells and on tumor neovasculature in situ, are potential targets for tumor- and vascular-targeting therapy. This study aimed to develop a FGFR-mediated drug delivery system to target chemotherapeutic agents to FGFR-overexpressed tumor cells and tumor neovasculature endothelial cells in vitro and in vivo. Here we designed a truncated human basic fibroblast growth factor peptide (tbFGF), which was attached to the surface of cationic liposomal doxorubicin (LPs-DOX) and paclitaxel (LPs-PTX) via electrostatic force. Then we characterized the tbFGF-modified liposome (tbFGF-LPs) and examined internalization of doxorubicin in tumor cells (TRAMP-C1, B16) and HUVEC cells in vitro. In vivo, we evaluated the biodistribution and antitumor efficacy of tbFGF-LPs-DOX and tbFGF-LPs-PTX in C57BL/6J mice bearing TRAMP-C1 prostate carcinoma and B16 melanoma, respectively. The tbFGF-LPs-DOX significantly improved the uptake of doxorubicin in TRAMP-C1, B16 and HUVEC cells, respectively. Biodistribution study in B16 tumor-bearing mice showed that tbFGF-LPs-PTX achieved 7.1-fold (72.827+/-7.321mgh/L vs 10.292+/-0.775mgh/L, mean+/-SD, P<0.01) accumulation of paclitaxel in tumor tissue than those of free paclitaxel. More importantly, treatment of tumor-bearing mice with tbFGF-LPs-DOX and tbFGF-LPs-PTX showed the significant inhibition in tumor growth and improvement in survival rate as compared with mice treated with free and liposomal drugs in TRAMP-C1 and B16 tumor models, respectively. Furthermore, repeated intravenous administration of tbFGF-LPs-DOX/PTX did not induce anti-bFGF antibodies. These results suggested that this FGFR-mediated drug delivery system may provide a new treatment strategy for tumors which overexpress FGFRs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1873-4995
pubmed:author
pubmed:copyrightInfo
2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
145
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-25
pubmed:meshHeading
pubmed-meshheading:20307599-Animals, pubmed-meshheading:20307599-Antineoplastic Agents, pubmed-meshheading:20307599-Cations, pubmed-meshheading:20307599-Cell Line, Tumor, pubmed-meshheading:20307599-Doxorubicin, pubmed-meshheading:20307599-Drug Carriers, pubmed-meshheading:20307599-Female, pubmed-meshheading:20307599-Fibroblast Growth Factor 2, pubmed-meshheading:20307599-Flow Cytometry, pubmed-meshheading:20307599-In Situ Nick-End Labeling, pubmed-meshheading:20307599-Injections, Intravenous, pubmed-meshheading:20307599-Liposomes, pubmed-meshheading:20307599-Male, pubmed-meshheading:20307599-Melanoma, Experimental, pubmed-meshheading:20307599-Mice, pubmed-meshheading:20307599-Mice, Inbred C57BL, pubmed-meshheading:20307599-Microscopy, Atomic Force, pubmed-meshheading:20307599-Neoplasm Transplantation, pubmed-meshheading:20307599-Paclitaxel, pubmed-meshheading:20307599-Particle Size, pubmed-meshheading:20307599-Prostatic Neoplasms, pubmed-meshheading:20307599-Protein Binding, pubmed-meshheading:20307599-Receptors, Fibroblast Growth Factor, pubmed-meshheading:20307599-Surface Properties
pubmed:year
2010
pubmed:articleTitle
Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide.
pubmed:affiliation
West China Hospital, Sichuan University, Chengdu, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't