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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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 |
format | Article |
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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]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2010.03.007</identifier><identifier>PMID: 20307599</identifier><identifier>CODEN: JCREEC</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>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</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. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-d38a06ced05386d5275ced49e7408ffcb3ae130709d8da84ba357d71edd085253</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168365910002129$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22908453$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20307599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiang</creatorcontrib><creatorcontrib>Wang, Xianhuo</creatorcontrib><creatorcontrib>Wang, Yongsheng</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Hu, Jia</creatorcontrib><creatorcontrib>Xiao, Wenjing</creatorcontrib><creatorcontrib>Fu, Afu</creatorcontrib><creatorcontrib>Cai, Lulu</creatorcontrib><creatorcontrib>Li, Xia</creatorcontrib><creatorcontrib>Ye, Xia</creatorcontrib><creatorcontrib>Liu, Yalin</creatorcontrib><creatorcontrib>Wu, Wenshuang</creatorcontrib><creatorcontrib>Shao, Ximing</creatorcontrib><creatorcontrib>Mao, Yongqiu</creatorcontrib><creatorcontrib>Wei, Yuquan</creatorcontrib><creatorcontrib>Chen, Lijuan</creatorcontrib><title>Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><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]</description><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cations</subject><subject>Cell Line, Tumor</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - pharmacokinetics</subject><subject>Doxorubicin - therapeutic use</subject><subject>Drug Carriers - chemistry</subject><subject>Drug delivery system</subject><subject>Female</subject><subject>FGF receptors</subject><subject>Fibroblast Growth Factor 2 - chemistry</subject><subject>Flow Cytometry</subject><subject>General pharmacology</subject><subject>In Situ Nick-End Labeling</subject><subject>Injections, Intravenous</subject><subject>Liposomes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Melanoma, Experimental - metabolism</subject><subject>Melanoma, Experimental - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Atomic Force</subject><subject>Neoplasm Transplantation</subject><subject>Paclitaxel - administration & dosage</subject><subject>Paclitaxel - pharmacokinetics</subject><subject>Paclitaxel - therapeutic use</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Protein Binding</subject><subject>Receptors, Fibroblast Growth Factor - metabolism</subject><subject>Surface Properties</subject><subject>Tumor-targeting</subject><subject>Vascular-targeting</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvLTwD5gnrK4sR2bJ8QqthSqRIXerYce9J6lcTBdhbl3-PVbuFYLrZm9MzHOy9CH2qyrUndft5v9zZMEYZtQ0qO0C0h4hXa1FLQiinFX6NN4WRFW64u0LuU9oQQTpl4iy4aQongSm3QejfOMRzA4byMIVbZxEfIfnrELi7lgcEfIK7YTIV4gmhmWLK3GPreW2NX3K3YmuzDVJKDn0MKI-AxON_70vS3z084x2UqTAm73e0OzzBn7-AKvenNkOD9-b9ED7tvP2--V_c_bu9uvt5XlnGZK0elIa0FV3aXreON4CVgCgQjsu9tRw3URQ1RTjojWWcoF07U4ByRvOH0El2f-hadvxZIWY8-WRgGM0FYkpaibRhTkr5ICs5kq_6np6C0ppy1spD8RNoYUorQ6zn60cRV10QfjdR7fTZSH43UhOpiZKn7eJ6wdCO4v1XPzhXg0xkwyZqhj2ayPv3jGkUk40dRX04clBsfPESdrIep3NBHsFm74F9Y5Q-PZsBc</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Chen, Xiang</creator><creator>Wang, Xianhuo</creator><creator>Wang, Yongsheng</creator><creator>Yang, Li</creator><creator>Hu, Jia</creator><creator>Xiao, Wenjing</creator><creator>Fu, Afu</creator><creator>Cai, Lulu</creator><creator>Li, Xia</creator><creator>Ye, Xia</creator><creator>Liu, Yalin</creator><creator>Wu, Wenshuang</creator><creator>Shao, Ximing</creator><creator>Mao, Yongqiu</creator><creator>Wei, Yuquan</creator><creator>Chen, Lijuan</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20100701</creationdate><title>Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-d38a06ced05386d5275ced49e7408ffcb3ae130709d8da84ba357d71edd085253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cations</topic><topic>Cell Line, Tumor</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - pharmacokinetics</topic><topic>Doxorubicin - therapeutic use</topic><topic>Drug Carriers - chemistry</topic><topic>Drug delivery system</topic><topic>Female</topic><topic>FGF receptors</topic><topic>Fibroblast Growth Factor 2 - chemistry</topic><topic>Flow Cytometry</topic><topic>General pharmacology</topic><topic>In Situ Nick-End Labeling</topic><topic>Injections, Intravenous</topic><topic>Liposomes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanoma, Experimental - drug therapy</topic><topic>Melanoma, Experimental - metabolism</topic><topic>Melanoma, Experimental - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Atomic Force</topic><topic>Neoplasm Transplantation</topic><topic>Paclitaxel - administration & dosage</topic><topic>Paclitaxel - pharmacokinetics</topic><topic>Paclitaxel - therapeutic use</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Protein Binding</topic><topic>Receptors, Fibroblast Growth Factor - metabolism</topic><topic>Surface Properties</topic><topic>Tumor-targeting</topic><topic>Vascular-targeting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiang</creatorcontrib><creatorcontrib>Wang, Xianhuo</creatorcontrib><creatorcontrib>Wang, Yongsheng</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Hu, Jia</creatorcontrib><creatorcontrib>Xiao, Wenjing</creatorcontrib><creatorcontrib>Fu, Afu</creatorcontrib><creatorcontrib>Cai, Lulu</creatorcontrib><creatorcontrib>Li, Xia</creatorcontrib><creatorcontrib>Ye, Xia</creatorcontrib><creatorcontrib>Liu, Yalin</creatorcontrib><creatorcontrib>Wu, Wenshuang</creatorcontrib><creatorcontrib>Shao, Ximing</creatorcontrib><creatorcontrib>Mao, Yongqiu</creatorcontrib><creatorcontrib>Wei, Yuquan</creatorcontrib><creatorcontrib>Chen, Lijuan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiang</au><au>Wang, Xianhuo</au><au>Wang, Yongsheng</au><au>Yang, Li</au><au>Hu, Jia</au><au>Xiao, Wenjing</au><au>Fu, Afu</au><au>Cai, Lulu</au><au>Li, Xia</au><au>Ye, Xia</au><au>Liu, Yalin</au><au>Wu, Wenshuang</au><au>Shao, Ximing</au><au>Mao, Yongqiu</au><au>Wei, Yuquan</au><au>Chen, Lijuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>145</volume><issue>1</issue><spage>17</spage><epage>25</epage><pages>17-25</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><coden>JCREEC</coden><abstract>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]</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>20307599</pmid><doi>10.1016/j.jconrel.2010.03.007</doi><tpages>9</tpages></addata></record> |
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source | MEDLINE; Elsevier ScienceDirect Journals |
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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