Synergistic Anti-Angiogenic Effects Using Peptide-Based Combinatorial Delivery of siRNAs Targeting VEGFA, VEGFR1, and Endoglin Genes

Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-β-...

Full description

Saved in:
Bibliographic Details
Published inPharmaceutics Vol. 11; no. 6; p. 261
Main Authors Egorova, Anna A, Shtykalova, Sofia V, Maretina, Marianna A, Sokolov, Dmitry I, Selkov, Sergei A, Baranov, Vladislav S, Kiselev, Anton V
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 06.06.2019
MDPI
Subjects
Angiogenesis
Apoptosis
Cytotoxicity
endoglin
endothelial cells
Endothelium
Gene expression
gene silencing
Growth factors
Hypoxia
Kinases
Ligands
migration
Mutation
peptide
Peptides
Prenatal development
proliferation
siRNA delivery
Tumors
VEGFA
VEGFR1
United States > US
Finland
Russia
endothelial cells
peptide
VEGFR1
proliferation
angiogenesis
gene silencing
migration
siRNA delivery
endoglin
VEGFA
Online AccessGet full text

Cover

Abstract Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-β-pathways, and some others. Introduction of small interfering RNA (siRNA) against genes of pro-angogenic factors is a promising strategy for the therapeutic suppression of angiogenesis. These siRNA molecules need to be specifically delivered into endothelial cells, and non-viral carriers modified with cellular receptor ligands can be proposed as perspective delivery systems for anti-angiogenic therapy purposes. Here we used modular peptide carrier L1, containing a ligand for the CXCR4 receptor, for the delivery of siRNAs targeting expression of VEGFA, VEGFR1 and endoglin genes. Transfection properties of siRNA/L1 polyplexes were studied in CXCR4-positive breast cancer cells MDA-MB-231 and endothelial cells EA.Hy926. We have demonstrated the efficient down-regulation of endothelial cells migration and proliferation by anti-VEGFA, anti-VEGFR1, and anti-endoglin siRNA-induced silencing. It was found that the efficiency of anti-angiogenic treatment can be synergistically improved via the combinatorial delivery of anti-VEGFA and anti-VEGFR1 siRNAs. Thus, this approach can be useful for the development of therapeutic angiogenesis inhibition.
AbstractList Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-β-pathways, and some others. Introduction of small interfering RNA (siRNA) against genes of pro-angogenic factors is a promising strategy for the therapeutic suppression of angiogenesis. These siRNA molecules need to be specifically delivered into endothelial cells, and non-viral carriers modified with cellular receptor ligands can be proposed as perspective delivery systems for anti-angiogenic therapy purposes. Here we used modular peptide carrier L1, containing a ligand for the CXCR4 receptor, for the delivery of siRNAs targeting expression of VEGFA, VEGFR1 and endoglin genes. Transfection properties of siRNA/L1 polyplexes were studied in CXCR4-positive breast cancer cells MDA-MB-231 and endothelial cells EA.Hy926. We have demonstrated the efficient down-regulation of endothelial cells migration and proliferation by anti-VEGFA, anti-VEGFR1, and anti-endoglin siRNA-induced silencing. It was found that the efficiency of anti-angiogenic treatment can be synergistically improved via the combinatorial delivery of anti-VEGFA and anti-VEGFR1 siRNAs. Thus, this approach can be useful for the development of therapeutic angiogenesis inhibition.
Author Selkov, Sergei A
Kiselev, Anton V
Sokolov, Dmitry I
Baranov, Vladislav S
Shtykalova, Sofia V
Egorova, Anna A
Maretina, Marianna A
AuthorAffiliation 2 Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia; sofia.shtykalova@gmail.com
1 D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia; egorova_anna@yahoo.com (A.A.E.); marianna0204@gmail.com (M.A.M.); falcojugger@yandex.ru (D.I.S.); selkovsa@mail.ru (S.A.S.); baranov@vb2475.spb.edu (V.S.B.)
AuthorAffiliation_xml – name: 1 D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia; egorova_anna@yahoo.com (A.A.E.); marianna0204@gmail.com (M.A.M.); falcojugger@yandex.ru (D.I.S.); selkovsa@mail.ru (S.A.S.); baranov@vb2475.spb.edu (V.S.B.)
– name: 2 Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia; sofia.shtykalova@gmail.com
Author_xml – sequence: 1
  givenname: Anna A
  surname: Egorova
  fullname: Egorova, Anna A
  email: egorova_anna@yahoo.com
  organization: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. egorova_anna@yahoo.com
– sequence: 2
  givenname: Sofia V
  surname: Shtykalova
  fullname: Shtykalova, Sofia V
  email: sofia.shtykalova@gmail.com
  organization: Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia. sofia.shtykalova@gmail.com
– sequence: 3
  givenname: Marianna A
  surname: Maretina
  fullname: Maretina, Marianna A
  email: marianna0204@gmail.com
  organization: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. marianna0204@gmail.com
– sequence: 4
  givenname: Dmitry I
  surname: Sokolov
  fullname: Sokolov, Dmitry I
  email: falcojugger@yandex.ru
  organization: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. falcojugger@yandex.ru
– sequence: 5
  givenname: Sergei A
  surname: Selkov
  fullname: Selkov, Sergei A
  email: selkovsa@mail.ru
  organization: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. selkovsa@mail.ru
– sequence: 6
  givenname: Vladislav S
  surname: Baranov
  fullname: Baranov, Vladislav S
  email: baranov@vb2475.spb.edu, baranov@vb2475.spb.edu
  organization: Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia. baranov@vb2475.spb.edu
– sequence: 7
  givenname: Anton V
  orcidid: 0000-0002-2487-2423
  surname: Kiselev
  fullname: Kiselev, Anton V
  email: ankiselev@yahoo.co.uk
  organization: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. ankiselev@yahoo.co.uk
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31174285$$D View this record in MEDLINE/PubMed
BookMark eNptkl1vFCEUhompsbX2J2hIvO0oHwPM3Jis63Zt0qiprbeEGQ5TNrOwwmyTvfeHS7u1aRO5OXy873MOcF6jgxADIPSWkg-ct-Tj5saktelhO_k-U0okYZK-QEe0bduqbhk_eDI_RCc5r0gZnNOGt6_QIadU1awRR-jPz12ANPhcSHgWJl_NwuDjAKGsF85BP2V8nX0Y8A_YTN5C9dlksHge150PZorJmxF_gdHfQtrh6HD2l99mGV-ZNMB0Z_y1WJ7NTu_DJT3FJli8CDYOow94CQHyG_TSmTHDyUM8Rtdni6v51-ri-_J8PruoekHEVLWW855Ta5TtAZSoqaIgSK1sw1pCG9l1veONcJRLUjslTCs6Z51QbV10HT9G53uujWalN8mvTdrpaLy-34hp0CaVhxhBF7YFoVjDuasVVY1yojaSUVUyyJ4V1qc9a7Pt1lAKClMy4zPo85Pgb_QQb7WUnEouCuD9AyDF31vIk17FbQrl_poJQRirmeRFJfaqPsWcE7jHDJTou17Q_-2F4nv3tLxH17-f538Br1W0rQ
CitedBy_id crossref_primary_10_1134_S1022795421090118
crossref_primary_10_3390_cancers12123744
crossref_primary_10_3390_cancers13215414
crossref_primary_10_3390_ph13100300
crossref_primary_10_1186_s43556_023_00126_2
crossref_primary_10_3390_ijms25010013
crossref_primary_10_1007_s11095_020_02904_x
crossref_primary_10_3390_pharmaceutics13071009
crossref_primary_10_3390_pharmaceutics12020178
crossref_primary_10_1016_j_onano_2023_100136
crossref_primary_10_3390_pharmaceutics15082108
crossref_primary_10_3390_ph14100957
crossref_primary_10_3390_pharmaceutics14040866
Cites_doi 10.1002/adfm.201800732
10.1016/S0167-4781(00)00220-7
10.1016/j.ajps.2018.01.006
10.3892/ol.2018.8733
10.1080/23723556.2015.1024821
10.1073/pnas.80.12.3734
10.1038/s41388-018-0380-3
10.2174/1566523215666150126115501
10.2174/1381612043452640
10.1038/sj.onc.1203533
10.1007/s10384-007-0506-6
10.1038/35065016
10.1161/CIRCRESAHA.113.301078
10.1242/dev.126.6.1149
10.1007/978-1-4939-9220-1_5
10.1016/j.jconrel.2010.04.012
10.3390/biomedicines6030073
10.1016/j.bbcan.2014.05.002
10.1021/bc034220o
10.1007/s40495-015-0044-8
10.1038/s41434-018-0042-7
10.1161/CIRCRESAHA.115.306361
10.1038/sj.onc.1208644
10.1016/j.stemcr.2017.07.009
10.1038/nature10144
10.1038/nature04483
10.1155/2012/839151
10.1080/10717544.2017.1396385
10.1126/science.284.5419.1534
10.1038/nrc2524
10.1172/JCI200318181
10.1126/scisignal.259re1
10.1080/mic.10.3-4.359.370
10.1038/nrm3176
10.4161/cbt.8.23.10271
10.1016/j.jconrel.2015.08.032
10.1161/ATVBAHA.107.161521
10.1038/srep32363
10.1093/carcin/bgs144
10.1038/sj.mt.6300388
10.1016/j.ijpharm.2012.10.020
10.1152/ajpcell.2001.280.6.C1358
10.2174/156720111793663570
10.1038/nrd2742
10.1093/nar/gkm543
10.1016/j.addr.2007.11.007
10.1016/j.bbrc.2012.06.163
10.1097/FJC.0000000000000355
10.1038/nrc905
10.1111/j.1525-1438.2006.00658.x
10.1097/CAD.0b013e3283627a0b
10.1002/jgm.1366
10.1091/mbc.e09-12-1061
10.3390/ijms19123887
10.1021/acsnano.5b01263
10.1016/j.phrs.2009.11.013
10.1002/jgm.2811
10.1016/j.ijpharm.2016.10.049
10.1038/35078107
10.1016/j.placenta.2003.10.009
10.2174/18722156113079990021
10.1074/jbc.M803059200
ContentType Journal Article
Copyright 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2019 by the authors. 2019
Copyright_xml – notice: 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2019 by the authors. 2019
DBID NPM
AAYXX
CITATION
3V.
7XB
8FK
8G5
ABUWG
AFKRA
AZQEC
BENPR
CCPQU
DWQXO
GNUQQ
GUQSH
M2O
MBDVC
PIMPY
PQEST
PQQKQ
PQUKI
PRINS
Q9U
5PM
DOA
DOI 10.3390/pharmaceutics11060261
DatabaseName PubMed
CrossRef
ProQuest Central (Corporate)
ProQuest Central (purchase pre-March 2016)
ProQuest Central (Alumni) (purchase pre-March 2016)
Research Library (Alumni Edition)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials
AUTh Library subscriptions: ProQuest Central
ProQuest One Community College
ProQuest Central
ProQuest Central Student
Research Library Prep
Proquest Research Library
Research Library (Corporate)
Publicly Available Content Database
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
ProQuest Central Basic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle PubMed
CrossRef
Publicly Available Content Database
Research Library Prep
ProQuest Central Student
ProQuest Central Basic
ProQuest Central Essentials
ProQuest One Academic Eastern Edition
ProQuest Central (Alumni Edition)
ProQuest One Community College
Research Library (Alumni Edition)
ProQuest Central China
ProQuest Central
ProQuest One Academic UKI Edition
ProQuest Central Korea
ProQuest Research Library
ProQuest One Academic
ProQuest Central (Alumni)
DatabaseTitleList

PubMed
Publicly Available Content Database
CrossRef
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: BENPR
  name: AUTh Library subscriptions: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Pharmacy, Therapeutics, & Pharmacology
EISSN 1999-4923
ExternalDocumentID oai_doaj_org_article_417de572833f471787f54a6217f386c2
10_3390_pharmaceutics11060261
31174285
Genre Journal Article
GeographicLocations United States--US
Finland
Russia
GeographicLocations_xml – name: Finland
– name: Russia
– name: United States--US
GrantInformation_xml – fundername: Ministry of Science and Higher Education of the Russian Federation
  grantid: АААА-А19-119021290033-1
– fundername: President of Russian Federation scholarship
  grantid: SP-822.2018.4
– fundername: Russian Science Foundation
  grantid: 17-15-01230
GroupedDBID ---
3V.
53G
5VS
8G5
AADQD
ABDBF
ABUWG
ACGFO
ACIHN
AEAQA
AFKRA
AFZYC
ALMA_UNASSIGNED_HOLDINGS
AZQEC
BENPR
BPHCQ
CCPQU
DIK
DWQXO
EBD
ESX
F5P
FD6
GNUQQ
GROUPED_DOAJ
GUQSH
GX1
HH5
HYE
IHR
KQ8
M2O
M48
MK0
MODMG
M~E
NPM
OK1
P6G
PGMZT
PIMPY
PQQKQ
PROAC
RIG
RNS
RPM
TR2
TUS
AAYXX
CITATION
7XB
8FK
MBDVC
PQEST
PQUKI
PRINS
Q9U
5PM
ID FETCH-LOGICAL-c505t-9d33c31da7dcee754171e5047d8290186bbcf385f13604f75a95bfdf5794e50b3
IEDL.DBID RPM
ISSN 1999-4923
IngestDate Tue Oct 22 15:12:42 EDT 2024
Tue Sep 17 21:27:40 EDT 2024
Thu Oct 10 19:28:57 EDT 2024
Fri Aug 23 01:53:49 EDT 2024
Sat Sep 28 08:37:50 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 6
Keywords endothelial cells
peptide
VEGFR1
proliferation
angiogenesis
gene silencing
migration
siRNA delivery
endoglin
VEGFA
Language English
License Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c505t-9d33c31da7dcee754171e5047d8290186bbcf385f13604f75a95bfdf5794e50b3
ORCID 0000-0002-2487-2423
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631635/
PMID 31174285
PQID 2550224263
PQPubID 2032349
ParticipantIDs doaj_primary_oai_doaj_org_article_417de572833f471787f54a6217f386c2
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6631635
proquest_journals_2550224263
crossref_primary_10_3390_pharmaceutics11060261
pubmed_primary_31174285
PublicationCentury 2000
PublicationDate 20190606
PublicationDateYYYYMMDD 2019-06-06
PublicationDate_xml – month: 6
  year: 2019
  text: 20190606
  day: 6
PublicationDecade 2010
PublicationPlace Switzerland
PublicationPlace_xml – name: Switzerland
– name: Basel
PublicationTitle Pharmaceutics
PublicationTitleAlternate Pharmaceutics
PublicationYear 2019
Publisher MDPI AG
MDPI
Publisher_xml – name: MDPI AG
– name: MDPI
References ref13
ref57
ref15
ref59
ref14
ref58
ref53
ref52
ref11
ref55
ref10
ref54
ref17
ref16
ref19
ref18
Derbyshire (ref20) 1995; 1
Nassiri (ref21) 2011; 31
ref51
ref50
ref45
Warrington (ref56) 2005; 25
ref47
ref42
ref41
Gerber (ref12) 1999; 126
ref44
ref49
ref8
ref7
ref9
Müller (ref48) 2001; 410
ref4
ref3
ref6
ref5
ref40
Seetharam (ref64) 1995; 10
Zhou (ref43) 2015; 5
ref35
ref34
ref37
Egorova (ref39) 2019; 1974
ref36
ref31
ref30
ref33
ref32
ref2
ref1
Smirnov (ref26) 2015; 61
ref38
Clarke (ref70) 2013; 4
Pérez-Gómez (ref69) 2005; 24
ref24
ref68
ref23
ref67
ref25
ref63
ref22
ref66
ref65
ref28
ref27
Wu (ref46) 2012; 33
ref29
ref60
ref62
ref61
References_xml – ident: ref49
  doi: 10.1002/adfm.201800732
– ident: ref52
  doi: 10.1016/S0167-4781(00)00220-7
– ident: ref40
  doi: 10.1016/j.ajps.2018.01.006
– ident: ref7
  doi: 10.3892/ol.2018.8733
– ident: ref14
  doi: 10.1080/23723556.2015.1024821
– ident: ref41
  doi: 10.1073/pnas.80.12.3734
– ident: ref18
  doi: 10.1038/s41388-018-0380-3
– ident: ref44
  doi: 10.2174/1566523215666150126115501
– ident: ref33
  doi: 10.2174/1381612043452640
– ident: ref55
  doi: 10.1038/sj.onc.1203533
– ident: ref17
  doi: 10.1007/s10384-007-0506-6
– volume: 5
  start-page: 3149
  year: 2015
  ident: ref43
  article-title: A VEGFR1 antagonistic peptide inhibits tumor growth and metastasis through VEGFR1-PI3K-AKT signaling pathway inhibition
  publication-title: Am. J. Cancer Res.
  contributor:
    fullname: Zhou
– volume: 410
  start-page: 50
  year: 2001
  ident: ref48
  article-title: Involvement of chemokine receptors in breast cancer metastasis
  publication-title: Nature
  doi: 10.1038/35065016
  contributor:
    fullname: Müller
– ident: ref1
  doi: 10.1161/CIRCRESAHA.113.301078
– volume: 126
  start-page: 1149
  year: 1999
  ident: ref12
  article-title: VEGF is required for growth and survival in neonatal mice
  publication-title: Development
  doi: 10.1242/dev.126.6.1149
  contributor:
    fullname: Gerber
– volume: 1974
  start-page: 57
  year: 2019
  ident: ref39
  article-title: VEGFA Gene Silencing in CXCR4-Expressing Cells via siRNA Delivery by Means of Targeted Peptide Carrier
  publication-title: Methods Mol. Biol.
  doi: 10.1007/978-1-4939-9220-1_5
  contributor:
    fullname: Egorova
– ident: ref45
  doi: 10.1016/j.jconrel.2010.04.012
– ident: ref61
  doi: 10.3390/biomedicines6030073
– ident: ref3
  doi: 10.1016/j.bbcan.2014.05.002
– ident: ref29
  doi: 10.1021/bc034220o
– ident: ref32
  doi: 10.1007/s40495-015-0044-8
– ident: ref38
  doi: 10.1038/s41434-018-0042-7
– ident: ref4
  doi: 10.1161/CIRCRESAHA.115.306361
– volume: 24
  start-page: 4450
  year: 2005
  ident: ref69
  article-title: Characterization of murine S-endoglin isoform and its effects on tumor development
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1208644
  contributor:
    fullname: Pérez-Gómez
– ident: ref68
  doi: 10.1016/j.stemcr.2017.07.009
– ident: ref62
  doi: 10.1038/nature10144
– ident: ref2
  doi: 10.1038/nature04483
– volume: 61
  start-page: 898
  year: 2015
  ident: ref26
  article-title: Endoglin (CD105) - A target for visualization and anti-angiogenic therapy for malignant tumors
  publication-title: Vopr. Onkol.
  contributor:
    fullname: Smirnov
– ident: ref9
  doi: 10.1155/2012/839151
– volume: 4
  start-page: 253
  year: 2013
  ident: ref70
  article-title: Understanding and targeting resistance to anti-angiogenic therapies
  publication-title: J. Gastrointest. Oncol.
  contributor:
    fullname: Clarke
– ident: ref59
  doi: 10.1080/10717544.2017.1396385
– ident: ref22
  doi: 10.1126/science.284.5419.1534
– ident: ref16
  doi: 10.1038/nrc2524
– ident: ref13
  doi: 10.1172/JCI200318181
– ident: ref19
  doi: 10.1126/scisignal.259re1
– ident: ref34
  doi: 10.1080/mic.10.3-4.359.370
– ident: ref53
  doi: 10.1038/nrm3176
– ident: ref60
  doi: 10.4161/cbt.8.23.10271
– ident: ref66
  doi: 10.1016/j.jconrel.2015.08.032
– ident: ref10
  doi: 10.1161/ATVBAHA.107.161521
– ident: ref67
  doi: 10.1038/srep32363
– volume: 33
  start-page: 1193
  year: 2012
  ident: ref46
  article-title: N -α-Acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression
  publication-title: Carcinogenesis
  doi: 10.1093/carcin/bgs144
  contributor:
    fullname: Wu
– ident: ref30
  doi: 10.1038/sj.mt.6300388
– ident: ref35
  doi: 10.1016/j.ijpharm.2012.10.020
– ident: ref8
  doi: 10.1152/ajpcell.2001.280.6.C1358
– ident: ref25
  doi: 10.2174/156720111793663570
– ident: ref47
  doi: 10.1038/nrd2742
– ident: ref58
  doi: 10.1093/nar/gkm543
– ident: ref50
  doi: 10.1016/j.addr.2007.11.007
– ident: ref65
  doi: 10.1016/j.bbrc.2012.06.163
– ident: ref11
  doi: 10.1097/FJC.0000000000000355
– ident: ref5
  doi: 10.1038/nrc905
– ident: ref23
  doi: 10.1111/j.1525-1438.2006.00658.x
– ident: ref15
  doi: 10.1097/CAD.0b013e3283627a0b
– ident: ref31
  doi: 10.1002/jgm.1366
– ident: ref54
  doi: 10.1091/mbc.e09-12-1061
– ident: ref24
  doi: 10.3390/ijms19123887
– ident: ref51
  doi: 10.1021/acsnano.5b01263
– volume: 25
  start-page: 1851
  year: 2005
  ident: ref56
  article-title: Functional role of CD105 in TGF-β1 signalling in murine and human endothelial cells
  publication-title: Anticancer Res.
  contributor:
    fullname: Warrington
– ident: ref28
  doi: 10.1016/j.phrs.2009.11.013
– ident: ref36
  doi: 10.1002/jgm.2811
– ident: ref37
  doi: 10.1016/j.ijpharm.2016.10.049
– ident: ref42
– ident: ref27
  doi: 10.1038/35078107
– volume: 31
  start-page: 2283
  year: 2011
  ident: ref21
  article-title: Endoglin (CD105): A review of its role in angiogenesis and tumor diagnosis, progression and therapy
  publication-title: Anticancer Res.
  contributor:
    fullname: Nassiri
– ident: ref63
  doi: 10.1016/j.placenta.2003.10.009
– volume: 10
  start-page: 135
  year: 1995
  ident: ref64
  article-title: A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF
  publication-title: Oncogene
  contributor:
    fullname: Seetharam
– ident: ref6
  doi: 10.2174/18722156113079990021
– volume: 1
  start-page: 1623
  year: 1995
  ident: ref20
  article-title: Up-Regulation of Endoglin on Vascular Endothelial Cells in Human Solid Tumors: Implications for Diagnosis and Therapy
  publication-title: Clin. Cancer Res.
  contributor:
    fullname: Derbyshire
– ident: ref57
  doi: 10.1074/jbc.M803059200
SSID ssj0000331839
Score 2.2717774
Snippet Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with...
SourceID doaj
pubmedcentral
proquest
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
StartPage 261
SubjectTerms Angiogenesis
Apoptosis
Cytotoxicity
endoglin
endothelial cells
Endothelium
Gene expression
gene silencing
Growth factors
Hypoxia
Kinases
Ligands
migration
Mutation
peptide
Peptides
Prenatal development
proliferation
siRNA delivery
Tumors
VEGFA
VEGFR1
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV07T8MwELYQEwviTXjJA-rUQIwfIWOAFoREVZWC2CLHD6iEUkTK0J0fztkutEWVWJiiJLbs5D77vkvOnxE6ToghJIWBBGT8LGYyLWNJNI-tdGyDKMO9xMZdR9w8sNsn_jSz1ZfLCQvywOHFnTKSaqgAXpBamEgBX5YzKYBJW3ouVJh9k2wmmPJzMHVYzcKSHQpx_enby_QTcQ0-z229ROackdfsX0Q0f-dLzjig9hpanTBHnIcer6MlU22gRjc0OG7i_nQlVd3EDdydilKPN9Hn_dit8vOyzDivRoM4r54HQ4APnAcJ4xr7_AHcdYku2sQX4OA0hgkDgmcXmgNS8ZV5dYkcYzy0uB70OnmN-z6X3FV8bF2386Y_9EgTy0rjVqWHz8BksZO3rrfQQ7vVv7yJJzswxAqY0SjONKWKEi1TeHaTcjAGMTxhqfb_X89FWSowA7eEioTZlMuMl1ZbDqMcypV0Gy1Xw8rsIsyd1JnRQinNGByypJTCaGaVoqXUMkIn36Yo3oLQRgEBirNdsdB2EbpwBvsp7HSy_QVATzFBT_EXeiJ08G3uYjJ46wKiLMdszgSN0E6w_E8rFJANERuPUDqHibluzN-pBi9ethu4HZBfvvcf_d5HK8DcMp-zJg7Q8uj9wxwCOxqVR34gfAGCgQ5C
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: AUTh Library subscriptions: ProQuest Central
  dbid: BENPR
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Lj9MwEB5B98IF8SawIB_Qnmo2ju1kc0IptKyQqKrSRXuLHD-6lVBSNuXQOz-csZO2FK04RUkc2dGMPd-Mx98AvIuZZSzDiYRgPKFCZRVVzEjqlEcbTFsZKDa-TtPLK_HlWl73Abe2T6vcrYlhoTaN9jHyc4S-3twkKf-w_kl91Si_u9qX0LgPJwl6CskATkbj6Wy-j7LE3Ots3h3d4ejfn69vDqHiFm2fL8HEjoxS4O6_C3D-mzf5lyGaPIKHPYIkRSfyx3DP1k_gbNZ1uB2SxeFEVTskZ2R2IKfePoXf37b-tF-gZyZFvVnRol6uGlQjvO-ojFsS8gjIzCe8GEtHaOgMwYUDnWjvoqPGkk_2h0_o2JLGkXY1nxYtWYSccv_h9_HnSTEMlzkbElUbMq5Ns0RESzzNdfsMribjxcdL2ldioBoR0obmhnPNmVEZ_rvNpGAZszIWmQn7sBdpVWnHL6RjPI2Fy6TKZeWMkzjbsV3Fn8Ogbmr7Eoj0lGfWpFobIfCSx5VKrRFOa14poyJ4vxNFue4IN0p0VLzsyjtlF8HIC2zf2PNlhwfN7bLsp1-JAzaodoiluENzjKuUk0Kl6I_hsFOdRHC6E3fZT-K2PKhcBC86ye974ajh6LnJCLIjnTgaxvGbenUT6LsR4yEIlq_-3-VreIDYLA9ZaekpDDa3v-wbxD-b6m2v5H8AYToIqA
  priority: 102
  providerName: ProQuest
– databaseName: Scholars Portal Journals: Open Access
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9NAEF5V5cIFQXm5tNUeUE9xyWYfrg8IuSWhQqKKSoJ6s9b7SCNVdhunEr7zw5lZOw1B4cbJsr2W156Zne-zZ78l5H2fOcYSCCQA44NY6KSINbMy9hrRBjNOBomNb5fqYiq-XsvrHbISVOheYL2V2uF6UtPF7cnP--YTBPxHZJxA2T_c3ay__taQznBVJSBETwaozYXVfB3iD4MzRydO27k8_756I0sFMf9tCPTvQso_MtPoOXnWQUqatT7wguy4co8cj9sbNj06WU-xqnv0mI7XatXNS_Lre4PT_4JeM83K5TzOytm8Ar-C_VbbuKahsICOsQLGuvgMMp-lMJIAq0bODi5MP7tbrPBoaOVpPb-6zGo6CUXmeOGP4ZdR1gubK9ajurR0WNpqBhCXou51_YpMR8PJ-UXcLc0QG4BMyzi1nBvOrE7g2V0iBUuYk32R2PBj9lQVhfH8VHrGVV_4ROpUFt56CeEP7Qr-muyWVeneEipRA81ZZYwVAjZpv9DKWeGN4YW2OiInK1Pkd60CRw7MBW2Xb7VdRM7QYI-NUUA7HKgWs7yLxxw6bMEPAVxxD_kZhi0vhVZA0KDbygwicrAyd75yyhzoF0KegeIRedNa_vEuHFweqJyMSLLhExvd2DxTzm-CnjeAPkDFcv9_9PsdeQqQLg3FbOqA7C4XD-4QYNOyOAqB8Bv_tRnz
  priority: 102
  providerName: Scholars Portal
Title Synergistic Anti-Angiogenic Effects Using Peptide-Based Combinatorial Delivery of siRNAs Targeting VEGFA, VEGFR1, and Endoglin Genes
URI https://www.ncbi.nlm.nih.gov/pubmed/31174285
https://www.proquest.com/docview/2550224263
https://pubmed.ncbi.nlm.nih.gov/PMC6631635
https://doaj.org/article/417de572833f471787f54a6217f386c2
Volume 11
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Pb9owFLb647LLtK37kbZDPkw9EcDYTsgxdNBqEihidOotcvyDRmoT1LAD9_7he3aSUqaeeiECEuWh99nve-HzZ4R-DIgmJISBBGR86DMRZr4givtGWLZBpObOYmM2D65v2K9bfnuAeLsWxon2ZZb3ivuHXpHfOW3l-kH2W51YP5ldQpUEGsH7h-gQAPqiRXfTL7UwjerVOhRa-v76bvd0uIJyZ3ddsjvEUIgS2DffK0nOuf81uvm_avJFGZp-QO8b_ojjOs6P6EAXn9BFUt9728XL3XqqqosvcLKzpt6eoKffW7vWz5kz47jY5H5crPISQATvayPjCjsVAU6s3EVpfwxlTmGYNqCFtg064BX_1PdWzrHFpcFVvpjHFV46Rbm98M_kahp33WFBulgUCk8KVa6Az2Jrcl19RjfTyfLy2m_2YfAl8KONHylKJSVKhPDbdcgZCYnmAxYq9y_sKMgyaeiIG0KDATMhFxHPjDIcxjqcl9Ev6KgoC_0NYW4Nz7QKpFSMwSEaZCLQihkpaSaU8FCvTUW6ru02UmhTbBrTV9PoobFN2PPJ1i3bfVA-rtIGMykErAB0wKSogWIMc5ThTATQjUHYgRx66LxNd9oM4SqFXsvym2FAPfS1zvzzXVrkeCjcw8ReGPvfAJadeXeD3dM3X3mG3gFpi5xcLThHR5vHv_o7EKNN1kHH48k8WXTcgwV4nbFRxw2Of361E7k
link.rule.ids 230,315,730,783,787,867,888,2109,2228,21402,24332,27938,27939,33758,43819,53806,53808,74638
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3Nb9MwFLdgO8AFjc-FDfAB7VSzuP7IckLp1lJgq6rSod0ixx9dJZSUpRx65w_n2UlbiiZOURJHdvR-9vs9-_lnhN7H1FKaQEcCMt4lXCUFUdQI4pRnG1RbESQ2rkZyeM2_3IibdsKtbtMq12NiGKhNpf0c-SlQX-9uupJ9XPwk_tQov7raHqHxEO17qSpA9X6vPxpPNrMsMfOYTZutOwzi-9PF7XaquAbf549gojtOKWj330c4_82b_MsRDQ7Qk5ZB4qwx-VP0wJbP0Mm4qXDVwdPtjqq6g0_weCtOvXqOfn9b-d1-QZ4ZZ-VyTrJyNq8ARnDfSBnXOOQR4LFPeDGW9MDRGQwDBwTRPkQHxOIL-8MndKxw5XA9n4yyGk9DTrn_8Hv_0yDrhMuEdrAqDe6XppoBo8Ve5rp-ga4H_en5kLQnMRANDGlJUsOYZtSoBP7dJoLThFoR88SEddgzWRTasTPhKJMxd4lQqSiccQJ6O5Qr2Eu0V1alPURYeMkza6TWhnO4pHGhpDXcac0KZVSEPqxNkS8awY0cAhVvu_xe20Wo5w22Kez1ssOD6m6Wt90vhwYbgB1wKebAHcMo5QRXEuIxaLbU3Qgdr82dt524zreQi9CrxvKbWhggHCI3EaFkBxM7zdh9U85vg3w3cDwgweL1_6t8hx4Np1eX-eXn0dcj9Bh4Whoy1OQx2lve_bJvgAsti7ct4P8AF8oLog
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Nj9MwEB1BV0JcEN8EFvAB7amhcW0nmxNK2Zblq4pKF-0tcvzRrYSSsimH3vnhjJ20pWjFKWqbyo7m2fPGeX4GeBNRQ2mCAwnJ-DDkMilDSbUIrXRsgyojvMXG12l8fsE_XYrLTv_UdLLK7ZzoJ2pdK7dGPkDq69LNMGYD28ki8rPJu9XP0J0g5d60dsdp3IajhCOqenA0Gk_z2W7FJWIOv2m7jYdhrT9YXe2XjRvMg-44JnqQoLyP_03k818N5V9JaXIf7nVskmRt-B_ALVM9hJO8bXDTJ_P97qqmT05Ivjeq3jyC3982bueft2omWbVehlm1WNYIKfzc2ho3xGsKSO7EL9qEI0x6muAkggW1K9cRveTM_HDijg2pLWmWs2nWkLnXl7s_fh9_mGR9f5nRPpGVJuNK1wtkt8RZXjeP4WIynr8_D7tTGUKFbGkdppoxxaiWCT67SQSnCTUi4on272RP47JUlp0KS1kccZsImYrSaitw5ON9JXsCvaquzDMgwtmfGR0rpTnHSxqVMjaaW6VYKbUM4O02FMWqNd8osGhxsStujF0AIxew3c3OO9t_UV8vim4oFthhjRBEXsUspmacsazgMsbaDLsdq2EAx9twF92Aboo9_AJ42kZ-1wpDtGMVJwJIDjBx0I3DX6rllbfyRr6HhFg8_3-Tr-EOYr348nH6-QXcRcqWerFafAy99fUv8xJp0bp81eH9D28qD9Y
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Synergistic+Anti-Angiogenic+Effects+Using+Peptide-Based+Combinatorial+Delivery+of+siRNAs+Targeting+VEGFA%2C+VEGFR1%2C+and+Endoglin+Genes&rft.jtitle=Pharmaceutics&rft.au=Anna+A.+Egorova&rft.au=Sofia+V.+Shtykalova&rft.au=Marianna+A.+Maretina&rft.au=Dmitry+I.+Sokolov&rft.date=2019-06-06&rft.pub=MDPI+AG&rft.eissn=1999-4923&rft.volume=11&rft.issue=6&rft.spage=261&rft_id=info:doi/10.3390%2Fpharmaceutics11060261&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_417de572833f471787f54a6217f386c2
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1999-4923&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1999-4923&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1999-4923&client=summon