Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide

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 agent...

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Veröffentlicht in:Journal of controlled release 2010-07, Vol.145 (1), p.17-25
Hauptverfasser: Chen, Xiang, Wang, Xianhuo, Wang, Yongsheng, Yang, Li, Hu, Jia, Xiao, Wenjing, Fu, Afu, Cai, Lulu, Li, Xia, Ye, Xia, Liu, Yalin, Wu, Wenshuang, Shao, Ximing, Mao, Yongqiu, Wei, Yuquan, Chen, Lijuan
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container_issue 1
container_start_page 17
container_title Journal of controlled release
container_volume 145
creator Chen, Xiang
Wang, Xianhuo
Wang, Yongsheng
Yang, Li
Hu, Jia
Xiao, Wenjing
Fu, Afu
Cai, Lulu
Li, Xia
Ye, Xia
Liu, Yalin
Wu, Wenshuang
Shao, Ximing
Mao, Yongqiu
Wei, Yuquan
Chen, Lijuan
description 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/6 J 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 ± 7.321 mgh/L vs 10.292 ± 0.775 mgh/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. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2010.03.007
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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/6 J 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 ± 7.321 mgh/L vs 10.292 ± 0.775 mgh/L, mean ± SD, P &lt; 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. 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Pharmaceutical industry ; Pharmacology. Drug treatments ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Protein Binding ; Receptors, Fibroblast Growth Factor - metabolism ; Surface Properties ; Tumor-targeting ; Vascular-targeting</subject><ispartof>Journal of controlled release, 2010-07, Vol.145 (1), p.17-25</ispartof><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>2010 Elsevier B.V. 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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/6 J 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 ± 7.321 mgh/L vs 10.292 ± 0.775 mgh/L, mean ± SD, P &lt; 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. 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Pharmaceutical industry</subject><subject>Pharmacology. 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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/6 J 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. 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subjects Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Cations
Cell Line, Tumor
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
Doxorubicin - therapeutic use
Drug Carriers - chemistry
Drug delivery system
Female
FGF receptors
Fibroblast Growth Factor 2 - chemistry
Flow Cytometry
General pharmacology
In Situ Nick-End Labeling
Injections, Intravenous
Liposomes
Male
Medical sciences
Melanoma, Experimental - drug therapy
Melanoma, Experimental - metabolism
Melanoma, Experimental - pathology
Mice
Mice, Inbred C57BL
Microscopy, Atomic Force
Neoplasm Transplantation
Paclitaxel - administration & dosage
Paclitaxel - pharmacokinetics
Paclitaxel - therapeutic use
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Protein Binding
Receptors, Fibroblast Growth Factor - metabolism
Surface Properties
Tumor-targeting
Vascular-targeting
title Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide
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