Enhanced blood-brain-barrier penetrability and tumor-targeting efficiency by peptide-functionalized poly(amidoamine) dendrimer for the therapy of gliomas
Identifieur interne : 000839 ( Main/Exploration ); précédent : 000838; suivant : 000840Enhanced blood-brain-barrier penetrability and tumor-targeting efficiency by peptide-functionalized poly(amidoamine) dendrimer for the therapy of gliomas
Auteurs : Changliang Liu [République populaire de Chine] ; Zijian Zhao [République populaire de Chine] ; Houqian Gao [République populaire de Chine] ; Iman Rostami [République populaire de Chine] ; Qing You [République populaire de Chine] ; Xinru Jia [République populaire de Chine] ; Chen Wang [République populaire de Chine] ; Ling Zhu [République populaire de Chine] ; Yanlian Yang [République populaire de Chine]Source :
- Nanotheranostics [ 2206-7418 ] ; 2019.
Abstract
Glioblastoma is one of the most common primary tumor types of central nervous system (CNS) with high malignance and lethality. Although many treatment options are currently available, the therapy of brain cancers remains challenging because of blood-brain-barrier (BBB) which prevents most of the chemotherapeutics into the CNS. In this work, a poly(amidoamine) dendrimer-based carrier was fabricated and modified with angiopep-2 (Ang2) peptide that has been demonstrated to bind to low density lipoprotein receptor-relative protein-1 (LRP1) on the endothelial cells of BBB and could therefore induce BBB penetration of the carrier. To improve tumor-targeting effect towards the glioma sites, the dendrimer was simultaneously functionalized with an epidermal growth factor receptor (EGFR)-targeting peptide (EP-1) which was screened from a “one-bead one-compound” (OBOC) combinatorial library. EP-1 peptide was demonstrated to have high affinity and specificity to EGFR at both the molecular and cellular levels. The dual-targeting dendrimer exhibited outstanding BBB penetrability and glioma targeting efficiency both
Url:
DOI: 10.7150/ntno.38954
PubMed: 31687320
PubMed Central: 6821994
Affiliations:
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C" first="Changliang" last="Liu">Changliang Liu</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">University of Chinese Academy of Sciences, Beijing 100049, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing 100049</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhao, Zijian" sort="Zhao, Zijian" uniqKey="Zhao Z" first="Zijian" last="Zhao">Zijian Zhao</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, Houqian" sort="Gao, Houqian" uniqKey="Gao H" first="Houqian" last="Gao">Houqian Gao</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">University of Chinese Academy of Sciences, Beijing 100049, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing 100049</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Rostami, Iman" sort="Rostami, Iman" uniqKey="Rostami I" first="Iman" last="Rostami">Iman Rostami</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="You, Qing" sort="You, Qing" uniqKey="You Q" first="Qing" last="You">Qing You</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">University of Chinese Academy of Sciences, Beijing 100049, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing 100049</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Jia, Xinru" sort="Jia, Xinru" uniqKey="Jia X" first="Xinru" last="Jia">Xinru Jia</name><affiliation wicri:level="4"><nlm:aff id="A3">Department of Chemistry, Peking University, Beijing 100871, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, Peking University, Beijing 100871</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName><orgName type="university">Université de Pékin</orgName><placeName><settlement type="city">Pékin</settlement><region type="capitale">Pékin</region></placeName></affiliation></author><author><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">University of Chinese Academy of Sciences, Beijing 100049, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing 100049</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhu, Ling" sort="Zhu, Ling" uniqKey="Zhu L" first="Ling" last="Zhu">Ling Zhu</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yang, Yanlian" sort="Yang, Yanlian" uniqKey="Yang Y" first="Yanlian" last="Yang">Yanlian Yang</name><affiliation wicri:level="1"><nlm:aff id="A1">CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">University of Chinese Academy of Sciences, Beijing 100049, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing 100049</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">Nanotheranostics</title><idno type="eISSN">2206-7418</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Glioblastoma is one of the most common primary tumor types of central nervous system (CNS) with high malignance and lethality. Although many treatment options are currently available, the therapy of brain cancers remains challenging because of blood-brain-barrier (BBB) which prevents most of the chemotherapeutics into the CNS. In this work, a poly(amidoamine) dendrimer-based carrier was fabricated and modified with angiopep-2 (Ang2) peptide that has been demonstrated to bind to low density lipoprotein receptor-relative protein-1 (LRP1) on the endothelial cells of BBB and could therefore induce BBB penetration of the carrier. To improve tumor-targeting effect towards the glioma sites, the dendrimer was simultaneously functionalized with an epidermal growth factor receptor (EGFR)-targeting peptide (EP-1) which was screened from a “one-bead one-compound” (OBOC) combinatorial library. EP-1 peptide was demonstrated to have high affinity and specificity to EGFR at both the molecular and cellular levels. The dual-targeting dendrimer exhibited outstanding BBB penetrability and glioma targeting efficiency both <italic>in vitro</italic> and <italic>in vivo</italic>, which strikingly enhanced the anti-gliomas effect of the drugs and prolonged the survival of gliomas-bearing mice. These results show the potential of the dual-targeting dendrimer-based carrier in the therapy of gliomas through enhancing BBB penetrability and tumor targeting.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Goodenberger, Ml" uniqKey="Goodenberger M">ML Goodenberger</name></author><author><name sortKey="Jenkins, Rb" uniqKey="Jenkins R">RB Jenkins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Z" uniqKey="Tan Z">Z Tan</name></author><author><name sortKey="Song, L" uniqKey="Song L">L Song</name></author><author><name sortKey="Wu, W" uniqKey="Wu W">W Wu</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Zhu, J" uniqKey="Zhu J">J Zhu</name></author><author><name sortKey="Wu, G" uniqKey="Wu G">G Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Meir, Eg" uniqKey="Van Meir E">EG Van 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Vasquez</name></author><author><name sortKey="Diaz, C" uniqKey="Diaz C">C Diaz</name></author><author><name sortKey="Nova, D" uniqKey="Nova D">D Nova</name></author><author><name sortKey="Alderete, J" uniqKey="Alderete J">J Alderete</name></author><author><name sortKey="Guzman, L" uniqKey="Guzman L">L Guzman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vergara Jaque, A" uniqKey="Vergara Jaque A">A Vergara-Jaque</name></author><author><name sortKey="Comer, J" uniqKey="Comer J">J Comer</name></author><author><name sortKey="Monsalve, L" uniqKey="Monsalve L">L Monsalve</name></author><author><name sortKey="Gonzalez Nilo, Fd" uniqKey="Gonzalez Nilo F">FD Gonzalez-Nilo</name></author><author><name sortKey="Sandoval, C" uniqKey="Sandoval C">C Sandoval</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Bryantsev, Vs" uniqKey="Bryantsev V">VS Bryantsev</name></author><author><name sortKey="Diallo, Ms" uniqKey="Diallo M">MS Diallo</name></author><author><name sortKey="Goddard Iii, Wa" uniqKey="Goddard Iii W">WA Goddard Iii</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Senapati, S" uniqKey="Senapati S">S Senapati</name></author><author><name sortKey="Mahanta, Ak" uniqKey="Mahanta A">AK Mahanta</name></author><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author><author><name sortKey="Maiti, P" uniqKey="Maiti P">P Maiti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cao, N" uniqKey="Cao N">N Cao</name></author><author><name sortKey="Feng, Ss" uniqKey="Feng S">SS Feng</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Pékin</li></region><settlement><li>Pékin</li></settlement><orgName><li>Université de Pékin</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Liu, Changliang" sort="Liu, Changliang" uniqKey="Liu C" first="Changliang" last="Liu">Changliang Liu</name></noRegion><name sortKey="Gao, Houqian" sort="Gao, Houqian" uniqKey="Gao H" first="Houqian" last="Gao">Houqian Gao</name><name sortKey="Gao, Houqian" sort="Gao, Houqian" uniqKey="Gao H" first="Houqian" last="Gao">Houqian Gao</name><name sortKey="Jia, Xinru" sort="Jia, Xinru" uniqKey="Jia X" first="Xinru" last="Jia">Xinru Jia</name><name sortKey="Liu, Changliang" sort="Liu, Changliang" uniqKey="Liu C" first="Changliang" last="Liu">Changliang Liu</name><name sortKey="Rostami, Iman" sort="Rostami, Iman" uniqKey="Rostami I" first="Iman" last="Rostami">Iman Rostami</name><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name><name sortKey="Yang, Yanlian" sort="Yang, Yanlian" uniqKey="Yang Y" first="Yanlian" last="Yang">Yanlian Yang</name><name sortKey="Yang, Yanlian" sort="Yang, Yanlian" uniqKey="Yang Y" first="Yanlian" last="Yang">Yanlian Yang</name><name sortKey="You, Qing" sort="You, Qing" uniqKey="You Q" first="Qing" last="You">Qing You</name><name sortKey="You, Qing" sort="You, Qing" uniqKey="You Q" first="Qing" last="You">Qing You</name><name sortKey="Zhao, Zijian" sort="Zhao, Zijian" uniqKey="Zhao Z" first="Zijian" last="Zhao">Zijian Zhao</name><name sortKey="Zhu, Ling" sort="Zhu, Ling" uniqKey="Zhu L" first="Ling" last="Zhu">Ling Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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