Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance
Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/2/133 |
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| author | Adriana Cruz Pedro Mota Cristiano Ramos Rita F. Pires Cindy Mendes José P. Silva Sofia C. Nunes Vasco D. B. Bonifácio Jacinta Serpa |
| author_facet | Adriana Cruz Pedro Mota Cristiano Ramos Rita F. Pires Cindy Mendes José P. Silva Sofia C. Nunes Vasco D. B. Bonifácio Jacinta Serpa |
| author_sort | Adriana Cruz |
| collection | DOAJ |
| description | Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to <span style="font-variant: small-caps;">l</span>-buthionine sulfoximine (<span style="font-variant: small-caps;">l</span>-BSO), an inhibitor of γ-glutamylcysteine ligase (GCL). Given the systemic toxicity of <span style="font-variant: small-caps;">l</span>-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (<span style="font-variant: small-caps;">l</span>-BSO@PURE<sub>G4</sub>-FA<sub>2</sub>), targeting <span style="font-variant: small-caps;">l</span>-BSO delivery in a folate functionalized nanoparticle. |
| first_indexed | 2024-03-12T06:41:28Z |
| format | Article |
| id | doaj.art-c21b74a4622446b9a643e59c5c375ee7 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T06:41:28Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c21b74a4622446b9a643e59c5c375ee72023-09-03T01:01:38ZengMDPI AGAntioxidants2076-39212020-02-019213310.3390/antiox9020133antiox9020133Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer ChemoresistanceAdriana Cruz0Pedro Mota1Cristiano Ramos2Rita F. Pires3Cindy Mendes4José P. Silva5Sofia C. Nunes6Vasco D. B. Bonifácio7Jacinta Serpa8iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, PortugaliBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, PortugalCEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, PortugaliBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, PortugalCEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, PortugalHospital Santo António dos Capuchos, Centro Hospitalar Lisboa Central, Alameda Santo António dos Capuchos, 1169-050 Lisboa, PortugalCEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, PortugaliBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, PortugalCEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, PortugalOvarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to <span style="font-variant: small-caps;">l</span>-buthionine sulfoximine (<span style="font-variant: small-caps;">l</span>-BSO), an inhibitor of γ-glutamylcysteine ligase (GCL). Given the systemic toxicity of <span style="font-variant: small-caps;">l</span>-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (<span style="font-variant: small-caps;">l</span>-BSO@PURE<sub>G4</sub>-FA<sub>2</sub>), targeting <span style="font-variant: small-caps;">l</span>-BSO delivery in a folate functionalized nanoparticle.https://www.mdpi.com/2076-3921/9/2/133ovarian cancerchemoresistance<span style="font-variant: small-caps">l</span>-buthionine sulfoximinepolyurea dendrimerscarboplatinnanoparticles-mediated chemotherapychemosensitization |
| spellingShingle | Adriana Cruz Pedro Mota Cristiano Ramos Rita F. Pires Cindy Mendes José P. Silva Sofia C. Nunes Vasco D. B. Bonifácio Jacinta Serpa Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance Antioxidants ovarian cancer chemoresistance <span style="font-variant: small-caps">l</span>-buthionine sulfoximine polyurea dendrimers carboplatin nanoparticles-mediated chemotherapy chemosensitization |
| title | Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance |
| title_full | Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance |
| title_fullStr | Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance |
| title_full_unstemmed | Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance |
| title_short | Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance |
| title_sort | polyurea dendrimer folate targeted nanodelivery of span style font variant small caps l span buthionine sulfoximine as a tool to tackle ovarian cancer chemoresistance |
| topic | ovarian cancer chemoresistance <span style="font-variant: small-caps">l</span>-buthionine sulfoximine polyurea dendrimers carboplatin nanoparticles-mediated chemotherapy chemosensitization |
| url | https://www.mdpi.com/2076-3921/9/2/133 |
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