A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells
Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an antican...
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| Veröffentlicht in: | PloS one 2013-06, Vol.8 (6), p.e66084-e66084 |
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| creator | Lim, Ki Jung Sung, Bong Hyun Shin, Ju Ri Lee, Young Woong Kim, Da Jung Yang, Kyung Seok Kim, Sun Chang |
| description | Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity. |
| doi_str_mv | 10.1371/journal.pone.0066084 |
| format | Article |
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However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0066084</identifier><identifier>PMID: 23776609</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino acids ; Apoptosis ; Apoptosis - physiology ; Biology ; Blotting, Western ; Cancer ; Cancer cells ; Cancer therapies ; Cancer treatment ; Cell Proliferation ; Cell-Penetrating Peptides - chemistry ; Cell-Penetrating Peptides - metabolism ; Cytotoxicity ; Derivatives ; Design ; Drug carriers ; Drug delivery ; Drug delivery systems ; Endocytosis - physiology ; Fibroblasts ; Gangliosides ; HCT116 Cells ; HeLa Cells ; Hemolysis - physiology ; Humans ; K-Ras protein ; Medicine ; Metastasis ; Microscopy ; Microscopy, Confocal ; Peptides ; Proteins ; Quantum dots ; Science ; Single-Chain Antibodies - chemistry ; Single-Chain Antibodies - metabolism ; Toxicity ; Translocation</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e66084-e66084</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Lim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Lim et al 2013 Lim et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1fbeeb7136965665c06760df770507183da31ab030be64dce04068f79d5f74723</citedby><cites>FETCH-LOGICAL-c692t-1fbeeb7136965665c06760df770507183da31ab030be64dce04068f79d5f74723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679022/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679022/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23776609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Sobol, Robert W.</contributor><creatorcontrib>Lim, Ki Jung</creatorcontrib><creatorcontrib>Sung, Bong Hyun</creatorcontrib><creatorcontrib>Shin, Ju Ri</creatorcontrib><creatorcontrib>Lee, Young Woong</creatorcontrib><creatorcontrib>Kim, Da Jung</creatorcontrib><creatorcontrib>Yang, Kyung Seok</creatorcontrib><creatorcontrib>Kim, Sun Chang</creatorcontrib><title>A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.</description><subject>Amino acids</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cancer treatment</subject><subject>Cell Proliferation</subject><subject>Cell-Penetrating Peptides - chemistry</subject><subject>Cell-Penetrating Peptides - metabolism</subject><subject>Cytotoxicity</subject><subject>Derivatives</subject><subject>Design</subject><subject>Drug carriers</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Endocytosis - physiology</subject><subject>Fibroblasts</subject><subject>Gangliosides</subject><subject>HCT116 Cells</subject><subject>HeLa Cells</subject><subject>Hemolysis - physiology</subject><subject>Humans</subject><subject>K-Ras protein</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Microscopy</subject><subject>Microscopy, Confocal</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Quantum dots</subject><subject>Science</subject><subject>Single-Chain Antibodies - chemistry</subject><subject>Single-Chain Antibodies - metabolism</subject><subject>Toxicity</subject><subject>Translocation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk19r2zAUxc3YWLtu32BsgsHYoMkky5bsl0FW1i1QKHR_XoUiXyUKjuRKcli__eTGKcnow_CDjPQ7R_ce-2bZa4KnhHLyae16b2U77ZyFKcaM4ap4kp2SmuYTlmP69OD9JHsRwhrjklaMPc9Ocsp5EtSn2WqGlLQKPAodKKONQgradtKBhehlNHaJOuiiaeAcfbnJz5F2HsUVINAJNmAjaqA1W_B3yGkkLQrqcouMjW7vPBiGl9kzLdsAr8b1LPt1-fXnxffJ1fW3-cXsaqJYnccJ0QuABSeU1axkrFSYcYYbzTkuMScVbSQlcoEpXgArGgW4wKzSvG5KzQue07Ps7c63a10QY0hBJEPGiionNBHzHdE4uRadNxvp74STRtxvOL8U0kejWhBSUyrLhrNK0oIoIqXSEiumgZWF5jh5fR5v6xcbSOXYFFp7ZHp8Ys1KLN1WUMZrnA_lfhgNvLvtIUSxMWEITFpw_X3d9dA2rRP67h_08e5GailTA8Zql-5Vg6mYFbyiecmroe7pI1R6GtgYlf4obdL-keDjkSAxEf7EpexDEPMfN__PXv8-Zt8fsCuQbVwF1_bROBuOwWIHKu9C8KAfQiZYDAOxT0MMAyHGgUiyN4cf6EG0nwD6F4PvBFU</recordid><startdate>20130611</startdate><enddate>20130611</enddate><creator>Lim, Ki Jung</creator><creator>Sung, Bong Hyun</creator><creator>Shin, Ju Ri</creator><creator>Lee, Young Woong</creator><creator>Kim, Da Jung</creator><creator>Yang, Kyung Seok</creator><creator>Kim, Sun Chang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130611</creationdate><title>A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells</title><author>Lim, Ki Jung ; Sung, Bong Hyun ; Shin, Ju Ri ; Lee, Young Woong ; Kim, Da Jung ; Yang, Kyung Seok ; Kim, Sun Chang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1fbeeb7136965665c06760df770507183da31ab030be64dce04068f79d5f74723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino acids</topic><topic>Apoptosis</topic><topic>Apoptosis - 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metabolism</topic><topic>Toxicity</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Ki Jung</creatorcontrib><creatorcontrib>Sung, Bong Hyun</creatorcontrib><creatorcontrib>Shin, Ju Ri</creatorcontrib><creatorcontrib>Lee, Young Woong</creatorcontrib><creatorcontrib>Kim, Da Jung</creatorcontrib><creatorcontrib>Yang, Kyung Seok</creatorcontrib><creatorcontrib>Kim, Sun Chang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Ki Jung</au><au>Sung, Bong Hyun</au><au>Shin, Ju Ri</au><au>Lee, Young Woong</au><au>Kim, Da Jung</au><au>Yang, Kyung Seok</au><au>Kim, Sun Chang</au><au>Sobol, Robert W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-06-11</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>e66084</spage><epage>e66084</epage><pages>e66084-e66084</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23776609</pmid><doi>10.1371/journal.pone.0066084</doi><tpages>e66084</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acids Apoptosis Apoptosis - physiology Biology Blotting, Western Cancer Cancer cells Cancer therapies Cancer treatment Cell Proliferation Cell-Penetrating Peptides - chemistry Cell-Penetrating Peptides - metabolism Cytotoxicity Derivatives Design Drug carriers Drug delivery Drug delivery systems Endocytosis - physiology Fibroblasts Gangliosides HCT116 Cells HeLa Cells Hemolysis - physiology Humans K-Ras protein Medicine Metastasis Microscopy Microscopy, Confocal Peptides Proteins Quantum dots Science Single-Chain Antibodies - chemistry Single-Chain Antibodies - metabolism Toxicity Translocation |
| title | A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells |
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