Coupling to a cancer-selective heparan-sulfate-targeted branched peptide can by-pass breast cancer cell resistance to methotrexate
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently...
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Published in | Oncotarget Vol. 8; no. 44; pp. 76141 - 76152 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Abstract | Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications. |
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AbstractList | Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines.
We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications. Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications. |
Author | Scali, Silvia Falciani, Chiara Bracci, Luisa Mandarini, Elisabetta Riolo, Giulia Depau, Lorenzo Brunetti, Jlenia Pini, Alessandro |
AuthorAffiliation | 1 Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy |
AuthorAffiliation_xml | – name: 1 Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy |
Author_xml | – sequence: 1 givenname: Lorenzo surname: Depau fullname: Depau, Lorenzo organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 2 givenname: Jlenia surname: Brunetti fullname: Brunetti, Jlenia organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 3 givenname: Chiara surname: Falciani fullname: Falciani, Chiara organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 4 givenname: Silvia surname: Scali fullname: Scali, Silvia organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 5 givenname: Giulia surname: Riolo fullname: Riolo, Giulia organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 6 givenname: Elisabetta surname: Mandarini fullname: Mandarini, Elisabetta organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 7 givenname: Alessandro surname: Pini fullname: Pini, Alessandro organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy – sequence: 8 givenname: Luisa surname: Bracci fullname: Bracci, Luisa organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy |
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CitedBy_id | crossref_primary_10_3389_fendo_2018_00069 crossref_primary_10_3390_ijms22147727 crossref_primary_10_1021_acs_molpharmaceut_2c00238 crossref_primary_10_1016_j_jconrel_2018_02_020 crossref_primary_10_1007_s00726_020_02860_1 crossref_primary_10_3892_ol_2018_9617 crossref_primary_10_1080_10837450_2019_1703739 crossref_primary_10_3389_fphar_2023_1052301 crossref_primary_10_3390_jpm11020088 crossref_primary_10_3389_fphar_2023_1188477 crossref_primary_10_1016_j_crphar_2021_100054 crossref_primary_10_1021_acs_jmedchem_0c01848 crossref_primary_10_1016_j_jconrel_2020_12_012 crossref_primary_10_3390_pharmaceutics14071378 crossref_primary_10_3389_fonc_2020_00882 crossref_primary_10_1002_pep2_24089 crossref_primary_10_14233_ajchem_2022_23566 crossref_primary_10_3389_fchem_2022_847573 crossref_primary_10_1039_D0MD00051E |
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Keywords | drug-resistance methotrexate peptides heparan sulfate |
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References | Hou (8) 2014; 42 Scatizzi (12) 2010; 10 Bracci (17) 2016; 6 Emonard (20) 2012; 32 Lehr (33) 2006; 62 Hassan (36) 2016; 17 Harashima (3) 2014; 37 van Kuppevelt (24) 2014; 135 Bracci (35) 2009; 9 Bracci (11) 2010; 5 Bracci (15) 2015; 5 Ratnam (27) 2004; 56 Morelli (13) 2011; 6 Bracci (10) 2007; 6 Deng (26) 2007; 26 Chen (30) 2015; 5 Gorlick (38) 2008; 8 Hou (7) 2008; 79 Guldberg (39) 2001; 276 Machado-Santelli (2) 2014; 33 Bracci (16) 2013; 56 Wu (22) 2013; 44 Wei (23) 2013; 140 Goldman (29) 2007; 26 Groninger (34) 2016; 13 Blobe (19) 2014; 39 Neri (37) 2003; 278 Dolmer (21) 2012; 443 Goldman (5) 2012; 26 Goldman (28) 2009; 11 Lee (25) 2015; 12 Plant (32) 2012; 7 Kerr (4) 2014; 39 Assaraf (6) 2012; 15 Goldman (9) 2003; 22 Roux (31) 2007; 1150 Johnston (1) 2013; 13 Sanderson (18) 2011; 15 Bracci (14) 2015; 2015 |
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Title | Coupling to a cancer-selective heparan-sulfate-targeted branched peptide can by-pass breast cancer cell resistance to methotrexate |
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