Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides
We previously reported that IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminus, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide repres...
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| Veröffentlicht in: | PloS one 2021-01, Vol.16 (1), p.e0241157-e0241157 |
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| creator | Nonaka, Motohiro Mabashi-Asazuma, Hideaki Jarvis, Donald L Yamasaki, Kazuhiko Akama, Tomoya O Nagaoka, Masato Sasai, Toshio Kimura-Takagi, Itsuko Suwa, Yoichi Yaegashi, Takashi Huang, Chun-Teng Nishizawa-Harada, Chizuko Fukuda, Michiko N |
| description | We previously reported that IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminus, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the ANXA1 N-terminus as target. We then identified peptide sequences, synthesized them as D-amino acids, and designated the resulting peptide dTIT7, which we showed bound to the ANXA1 N-terminus. Whole body imaging of mouse brain tumor models injected with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered dTIT7/geldanamycin (GA) conjugates suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that ANXA1-binding D-peptide can be developed as an orally-administrable tumor vasculature-targeted therapeutic. |
| doi_str_mv | 10.1371/journal.pone.0241157 |
| format | Article |
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To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the ANXA1 N-terminus as target. We then identified peptide sequences, synthesized them as D-amino acids, and designated the resulting peptide dTIT7, which we showed bound to the ANXA1 N-terminus. Whole body imaging of mouse brain tumor models injected with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered dTIT7/geldanamycin (GA) conjugates suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that ANXA1-binding D-peptide can be developed as an orally-administrable tumor vasculature-targeted therapeutic.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0241157</identifier><identifier>PMID: 33406123</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Administration, Oral ; Amino acids ; Animal models ; Animals ; Annexin A1 - antagonists & inhibitors ; Annexin A1 - metabolism ; Annexins ; Antigens ; Antimitotic agents ; Antineoplastic agents ; Binding ; Biology and Life Sciences ; Blood-vessels ; Brain ; Brain cancer ; Brain Neoplasms - blood supply ; Brain Neoplasms - drug therapy ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain tumors ; Carbohydrates ; D-Amino acids ; Dosage and administration ; Drug delivery ; Drug Delivery Systems ; Drug therapy ; Drugs ; Fluorescence ; Geldanamycin ; Health aspects ; Humans ; Image enhancement ; Intravenous administration ; Kidneys ; Laboratories ; Libraries ; Medicine and Health Sciences ; Melanoma ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular biology ; N-Terminus ; Neoplasm Proteins - antagonists & inhibitors ; Neoplasm Proteins - metabolism ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - metabolism ; Neovascularization, Pathologic - pathology ; Neuroimaging ; Peptides ; Peptides - chemical synthesis ; Peptides - chemistry ; Peptides - pharmacology ; Phage display ; Phages ; Pharmaceutical research ; Prostate cancer ; Proteins ; Research and Analysis Methods ; Synthetic products ; Target recognition ; Tumors ; Vehicles ; Xenograft Model Antitumor Assays</subject><ispartof>PloS one, 2021-01, Vol.16 (1), p.e0241157-e0241157</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Nonaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2021 Nonaka et al 2021 Nonaka et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-38b2a8e986b5859f974bbe381577279a5f463b43685ec9481023082b988880173</citedby><cites>FETCH-LOGICAL-c692t-38b2a8e986b5859f974bbe381577279a5f463b43685ec9481023082b988880173</cites><orcidid>0000-0003-4120-0490</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787448/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787448/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33406123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tsai, Yu-Hsuan</contributor><creatorcontrib>Nonaka, Motohiro</creatorcontrib><creatorcontrib>Mabashi-Asazuma, Hideaki</creatorcontrib><creatorcontrib>Jarvis, Donald L</creatorcontrib><creatorcontrib>Yamasaki, Kazuhiko</creatorcontrib><creatorcontrib>Akama, Tomoya O</creatorcontrib><creatorcontrib>Nagaoka, Masato</creatorcontrib><creatorcontrib>Sasai, Toshio</creatorcontrib><creatorcontrib>Kimura-Takagi, Itsuko</creatorcontrib><creatorcontrib>Suwa, Yoichi</creatorcontrib><creatorcontrib>Yaegashi, Takashi</creatorcontrib><creatorcontrib>Huang, Chun-Teng</creatorcontrib><creatorcontrib>Nishizawa-Harada, Chizuko</creatorcontrib><creatorcontrib>Fukuda, Michiko N</creatorcontrib><title>Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We previously reported that IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminus, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. 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Ours is a proof-of-concept experiment showing that ANXA1-binding D-peptide can be developed as an orally-administrable tumor vasculature-targeted therapeutic.</description><subject>Administration, Oral</subject><subject>Amino acids</subject><subject>Animal models</subject><subject>Animals</subject><subject>Annexin A1 - antagonists & inhibitors</subject><subject>Annexin A1 - metabolism</subject><subject>Annexins</subject><subject>Antigens</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Binding</subject><subject>Biology and Life Sciences</subject><subject>Blood-vessels</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - blood supply</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumors</subject><subject>Carbohydrates</subject><subject>D-Amino acids</subject><subject>Dosage and 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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>Nonaka, Motohiro</au><au>Mabashi-Asazuma, Hideaki</au><au>Jarvis, Donald L</au><au>Yamasaki, Kazuhiko</au><au>Akama, Tomoya O</au><au>Nagaoka, Masato</au><au>Sasai, Toshio</au><au>Kimura-Takagi, Itsuko</au><au>Suwa, Yoichi</au><au>Yaegashi, Takashi</au><au>Huang, Chun-Teng</au><au>Nishizawa-Harada, Chizuko</au><au>Fukuda, Michiko N</au><au>Tsai, Yu-Hsuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-01-06</date><risdate>2021</risdate><volume>16</volume><issue>1</issue><spage>e0241157</spage><epage>e0241157</epage><pages>e0241157-e0241157</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>We previously reported that IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminus, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the ANXA1 N-terminus as target. We then identified peptide sequences, synthesized them as D-amino acids, and designated the resulting peptide dTIT7, which we showed bound to the ANXA1 N-terminus. Whole body imaging of mouse brain tumor models injected with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered dTIT7/geldanamycin (GA) conjugates suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that ANXA1-binding D-peptide can be developed as an orally-administrable tumor vasculature-targeted therapeutic.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33406123</pmid><doi>10.1371/journal.pone.0241157</doi><tpages>e0241157</tpages><orcidid>https://orcid.org/0000-0003-4120-0490</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-01, Vol.16 (1), p.e0241157-e0241157 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2475831428 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Administration, Oral Amino acids Animal models Animals Annexin A1 - antagonists & inhibitors Annexin A1 - metabolism Annexins Antigens Antimitotic agents Antineoplastic agents Binding Biology and Life Sciences Blood-vessels Brain Brain cancer Brain Neoplasms - blood supply Brain Neoplasms - drug therapy Brain Neoplasms - metabolism Brain Neoplasms - pathology Brain tumors Carbohydrates D-Amino acids Dosage and administration Drug delivery Drug Delivery Systems Drug therapy Drugs Fluorescence Geldanamycin Health aspects Humans Image enhancement Intravenous administration Kidneys Laboratories Libraries Medicine and Health Sciences Melanoma Mice Mice, Inbred BALB C Mice, Nude Molecular biology N-Terminus Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - metabolism Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology Neuroimaging Peptides Peptides - chemical synthesis Peptides - chemistry Peptides - pharmacology Phage display Phages Pharmaceutical research Prostate cancer Proteins Research and Analysis Methods Synthetic products Target recognition Tumors Vehicles Xenograft Model Antitumor Assays |
| title | Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides |
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