Amrubicin encapsulated PLGA NPs inhibits the PI3K/AKT signaling pathway by activating PTEN and inducing apoptosis in TMZ-resistant Glioma

Abstract

Glioblastoma (GBM) is an aggressive and deadly brain tumor, and currently, there is no effective cure available for its treatment. Although nanotechnology-based strategies have shown great potential in treating GBM, a major concern is the lack of efficient clearance of these nanoparticles from the body's organs, which limits their translation from laboratory studies to clinical settings. To address this issue, a study was conducted to investigate the potential of using amrubicin (AMR) encapsulated in poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) against temozolomide (TMZ) resistant GBM. The study found that AMR-PLGA-NPs significantly inhibited the cell viability and migration of TMZ-resistant GBM cells. Additionally, the nanoparticles were effective in suppressing the PI3K/AKT signaling pathway, inducing apoptosis in TMZ-resistant glioma cancer cells and glioma stem-like cells (GSCs) by activating PTEN. Furthermore, AMR-PLGA-NPs can pass the biological barrier in in vivo mice model. These findings indicate that AMR-PLGA-NPs can be an effective and flexible nanoplatform for treating GBM while addressing drug resistance issues. Overall, the study demonstrates the potential of AMR-PLGA-NPs as a stable and safe treatment option for GBM, addressing the major issue of drug resistance in these types of tumors.