Polyurea Dendrimer Folate-Targeted Nanodelivery of <span style="font-variant: small-caps">l</span>-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance

• Main Authors: Adriana Cruz (Author), Pedro Mota (Author), Cristiano Ramos (Author), Rita F. Pires (Author), Cindy Mendes (Author), José P. Silva (Author), Sofia C. Nunes (Author), Vasco D. B. Bonifácio (Author), Jacinta Serpa (Author)
• Format: Book
• Published: MDPI AG, 2020-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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_G4-FA₂), targeting <span style="font-variant: small-caps;">l</span>-BSO delivery in a folate functionalized nanoparticle.

Item Description

2076-3921
10.3390/antiox9020133