Resensitization of temozolomide-resistant glioblastoma cells using ursolic acid nanocrystals - Micro et Nanomédecines Translationnelles Accéder directement au contenu
Poster De Conférence Année : 2022

Resensitization of temozolomide-resistant glioblastoma cells using ursolic acid nanocrystals

Résumé

Glioblastoma patients are currently treated following the Stupp protocol which consists of surgical removal of the tumor, followed by radio and chemotherapy using temozolomide (TMZ). One of the causes for treatment resistance is the expression of O6-methylguanine-DNA-methyltransferase (MGMT). MGMT naturally removes alkyl groups from DNA to protect and repair it [1]. However, the pharmacological action of TMZ is to add methyl groups to DNA to eliminate tumor cells. TMZ action is thus inhibited by MGMT and the proportion of patient with a MGMT-expressing glioblastoma is of around 45% [2]. The aim of this study is to inhibit the expression of MGMT to restore TMZ sensitivity. Here, ursolic acid (UA) has been used as a MGMT inhibitor. UA decreases the transcripts of MGMT and so the expression of the protein and improves TMZ toxicity with cotreatment on MGMT-positive cells [3]. UA has then been formulated in about 200 nm nanocrystals using an antisolvent crystallization method, in order to develop a local administration strategy post-resection. FRET signal inducing dyes were added to the UA nanocrystal formulation to allow the study of their internalization (effective after a 6h contact with MGMT-positive cells) and their degradation in cellulo (seeable after 48h). UA nanocrystals were also able to improve the sensitivity to TMZ even better than unimolecular UA. All together these preliminary results seem promising in the resensitization of TMZ-resistant glioblastoma patients.
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Dates et versions

hal-03880683 , version 1 (01-12-2022)

Identifiants

  • HAL Id : hal-03880683 , version 1

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Marion Sicot, Patrick Saulnier, Guillaume Bastiat. Resensitization of temozolomide-resistant glioblastoma cells using ursolic acid nanocrystals. SFNano Annual Meeting 2022, Dec 2022, Strasbourg, France. . ⟨hal-03880683⟩
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