Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance
by
Adriana Cruz 1,†, Pedro Mota 1,†, Cristiano Ramos 2,3, Rita F. Pires 1, Cindy Mendes 2,3, José P. Silva 4, Sofia C. Nunes 2,3, Vasco D. B. Bonifácio 1,*,† and Jacinta Serpa 2,3,*,†
Adriana Cruz 1,†, Pedro Mota 1,†, Cristiano Ramos 2,3, Rita F. Pires 1, Cindy Mendes 2,3, José P. Silva 4, Sofia C. Nunes 2,3, Vasco D. B. Bonifácio 1,*,† and Jacinta Serpa 2,3,*,†
1
iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, Portugal
2
CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
3
Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisboa, Portugal
4
Hospital Santo António dos Capuchos, Centro Hospitalar Lisboa Central, Alameda Santo António dos Capuchos, 1169-050 Lisboa, Portugal
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antioxidants 2020, 9(2), 133; https://doi.org/10.3390/antiox9020133
Received: 20 December 2019 / Revised: 29 January 2020 / Accepted: 31 January 2020 / Published: 3 February 2020
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
: 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 l-buthionine sulfoximine (l-BSO), an inhibitor of -glutamylcysteine ligase (GCL). Given the systemic toxicity of l-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles ([email protected]G4-FA2), targeting l-BSO delivery in a folate functionalized nanoparticle.
Keywords:
ovarian cancer; chemoresistance; l-buthionine sulfoximine; polyurea dendrimers; carboplatin; nanoparticles-mediated chemotherapy; chemosensitization
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Cruz, A.; Mota, P.; Ramos, C.; Pires, R.F.; Mendes, C.; Silva, J.P.; Nunes, S.C.; Bonifácio, V.D.B.; Serpa, J. Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance. Antioxidants 2020, 9, 133.
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