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Publicação
Dendrimer-based Report-Eradication Antineoplasic Machines
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Polyurea (PURE) dendrimers are a versatile platform for cancer nanotheranostics. The
aim of this study was to improve the therapeutic efficacy of carboplatin by a buthionine
sulfoximine (BSO) triggered inhibition of glutathione synthesis. BSO nanodelivery was
achieved by controlled release from an encapsulated formulation using a folate target
polyurea dendrimer of generation four (BSO@PUREG4-FA). Platinum-based anti-cancer drugs, such as cisplatin and carboplatin have been widely used in chemotherapy. In particular, carboplatins are used as standard chemotherapeutic in ovarian cancer, a silent killer, which is the most lethal gynecologic malignancy and the seventh most common cancer among women worldwide. However, carboplatin chemoresistance is a major problem and there is evidence that increased glutathione levels play an important role in the anticancer mechanism of action. Cell death assays using OVCAR3 (OSC) and ES2 (OCCC) ovarian cancer cell lines were used to determine the efficacy of BSO@PUREG4-FA nanoformulations. Cytotoxicity data showed that the encapsulated drug, if compared with the free drug, improve the efficacy of BSO, by reduction of the IC50, against both OVCAR3 (64-fold) and ES2 (146-fold) cell lines. The results showed that inhibition of glutathione synthesis improve the efficacy of carboplatin in both cell lines. In this study a new method for detection of BSO was also developed, based on UV detection upon BSO chemical derivatization.
Descrição
Palavras-chave
Ovarian cancer Buthionine sulfoximine Chemoresistance Glutathione Polyurea dendrimers Controlled drug delivery