Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer
Aptamers are emerging as a promising new class of functional nucleic acids because they can specifically bind to any target with high affinity and be easily modified chemically with different pharmacophoric subunits for therapy. The truncated aptamer, Sgc8-c, binds to tyrosine-protein kinase-like 7...
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| その他の著者: | , , |
| フォーマット: | article |
| 言語: | 英語 |
| 出版事項: |
2023
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| オンライン･アクセス: | https://hdl.handle.net/20.500.12008/54081 |
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| _version_ | 1868890177507688448 |
|---|---|
| author | Sicco, Estefanía |
| author2 | Cerecetto, Hugo Calzada, Victoria Moreno, María |
| author2_role | author author author |
| author_browse | Calzada, Victoria Cerecetto, Hugo Moreno, María Sicco, Estefanía |
| author_facet | Sicco, Estefanía Cerecetto, Hugo Calzada, Victoria Moreno, María |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Sicco Estefanía, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares Calzada Victoria, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares Moreno María, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene, Departamento de Desarrollo Biotecnológico |
| dc.creator.none.fl_str_mv | Sicco, Estefanía Cerecetto, Hugo Calzada, Victoria Moreno, María |
| dc.date.none.fl_str_mv | 2023 2026-03-25T12:58:29Z 2026-03-25T12:58:29Z |
| dc.format.none.fl_str_mv | 13 p. application/pdf |
| dc.identifier.none.fl_str_mv | Sicco E, Cerecetto H, Calzada V y otros. Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer. Cancers [en línea]. 2023;15(3). 13 p. https://hdl.handle.net/20.500.12008/54081 10.3390/cancers15030922 2072-6694 |
| dc.language.none.fl_str_mv | en eng |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.relation.none.fl_str_mv | Cancers. 2023;15(3) |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | PTK7 Aptamer Aptamer-drug conjugates Biotherapeutics Drug delivery Lymphoma APTÁMEROS DE NUCLEÓTIDOS ÁCIDOS NUCLEICOS PROTEÍNAS TIROSINA QUINASAS NEOPLASIAS NEOPLASIAS HEMATOLÓGICAS LINFOMA |
| dc.title.none.fl_str_mv | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | Aptamers are emerging as a promising new class of functional nucleic acids because they can specifically bind to any target with high affinity and be easily modified chemically with different pharmacophoric subunits for therapy. The truncated aptamer, Sgc8-c, binds to tyrosine-protein kinase-like 7 receptor, a promising cancer therapeutic target, allowing the recognition of haemato-oncological malignancies, among others. We have previously developed aptamer-drug conjugates by chemical synthesis, hybridizing Sgc8-c and dasatinib, a drug proposed for lymphoma chemotherapy. One of the best-characterised Sgc8-c-dasatinib hybrids, namely Sgc8-c-carb-da, was capable of releasing dasatinib at an endosomal-pH. Herein, we probed the therapeutic potential of this aptamer-drug conjugate. Sgc8-c-carb-da specifically inhibited murine A20 B lymphocyte growth and produced cell death, mainly by late apoptosis and necrosis. In addition, Sgc8-c-carb-da generated an arrest in cell proliferation, with a cell cycle arrest in the Sub-G1-peak. The mitochondrial potential was altered accordingly to these pathways. Moreover, using an in vitro cell-targeting assay that mimics in vivo conditions, we showed that Sgc8-c-carb-da displayed higher (2.5-fold) cytotoxic effects than dasatinib. These findings provide proof-of-concept of the therapeutic value of Sgc8-c-carb-da for lymphoma, creating new opportunities for the chemical synthesis of targeted biotherapeutics. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_bc2e79031182eec9d753adef3d03df65 |
| identifier_str_mv | Sicco E, Cerecetto H, Calzada V y otros. Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer. Cancers [en línea]. 2023;15(3). 13 p. 10.3390/cancers15030922 2072-6694 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/54081 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher.none.fl_str_mv | MDPI |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c AptamerSicco, EstefaníaCerecetto, HugoCalzada, VictoriaMoreno, MaríaPTK7AptamerAptamer-drug conjugatesBiotherapeuticsDrug deliveryLymphomaAPTÁMEROS DE NUCLEÓTIDOSÁCIDOS NUCLEICOSPROTEÍNAS TIROSINA QUINASASNEOPLASIASNEOPLASIAS HEMATOLÓGICASLINFOMAAptamers are emerging as a promising new class of functional nucleic acids because they can specifically bind to any target with high affinity and be easily modified chemically with different pharmacophoric subunits for therapy. The truncated aptamer, Sgc8-c, binds to tyrosine-protein kinase-like 7 receptor, a promising cancer therapeutic target, allowing the recognition of haemato-oncological malignancies, among others. We have previously developed aptamer-drug conjugates by chemical synthesis, hybridizing Sgc8-c and dasatinib, a drug proposed for lymphoma chemotherapy. One of the best-characterised Sgc8-c-dasatinib hybrids, namely Sgc8-c-carb-da, was capable of releasing dasatinib at an endosomal-pH. Herein, we probed the therapeutic potential of this aptamer-drug conjugate. Sgc8-c-carb-da specifically inhibited murine A20 B lymphocyte growth and produced cell death, mainly by late apoptosis and necrosis. In addition, Sgc8-c-carb-da generated an arrest in cell proliferation, with a cell cycle arrest in the Sub-G1-peak. The mitochondrial potential was altered accordingly to these pathways. Moreover, using an in vitro cell-targeting assay that mimics in vivo conditions, we showed that Sgc8-c-carb-da displayed higher (2.5-fold) cytotoxic effects than dasatinib. These findings provide proof-of-concept of the therapeutic value of Sgc8-c-carb-da for lymphoma, creating new opportunities for the chemical synthesis of targeted biotherapeutics.MDPISicco Estefanía, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones NuclearesCerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones NuclearesCalzada Victoria, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones NuclearesMoreno María, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene, Departamento de Desarrollo Biotecnológico2026-03-25T12:58:29Z2026-03-25T12:58:29Z2023Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfSicco E, Cerecetto H, Calzada V y otros. Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer. Cancers [en línea]. 2023;15(3). 13 p.https://hdl.handle.net/20.500.12008/5408110.3390/cancers150309222072-6694reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengCancers. 2023;15(3)Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/540812026-04-14T10:28:28Z |
| spellingShingle | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer Sicco, Estefanía PTK7 Aptamer Aptamer-drug conjugates Biotherapeutics Drug delivery Lymphoma APTÁMEROS DE NUCLEÓTIDOS ÁCIDOS NUCLEICOS PROTEÍNAS TIROSINA QUINASAS NEOPLASIAS NEOPLASIAS HEMATOLÓGICAS LINFOMA |
| status_str | publishedVersion |
| title | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| title_full | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| title_fullStr | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| title_full_unstemmed | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| title_short | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| title_sort | Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer |
| topic | PTK7 Aptamer Aptamer-drug conjugates Biotherapeutics Drug delivery Lymphoma APTÁMEROS DE NUCLEÓTIDOS ÁCIDOS NUCLEICOS PROTEÍNAS TIROSINA QUINASAS NEOPLASIAS NEOPLASIAS HEMATOLÓGICAS LINFOMA |
| url | https://hdl.handle.net/20.500.12008/54081 |