Targeting BMI-1 with PLGA–PEG nanoparticle-containing PTC209 modulates the behavior of human glioblastoma stem cells and cancer cells

Despite advances in glioblastoma (GBM) treatments, current approaches have failed to improve the overall survival of patients. The oncogene BMI-1, a core member of the polycomb group proteins, is a potential novel therapeutic target for GBM. To enhance the efficacy and reduce the toxicity, PTC209, a...

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Bibliographic Details
Published in:Cancer nanotechnology 2021-12, Vol.12 (1), p.1-20, Article 5
Main Authors: Poonaki, Elham, Ariakia, Fatemeh, Jalili-Nik, Mohammad, Shafiee Ardestani, Mehdi, Tondro, Gholamhossein, Samini, Fariborz, Ghasemi, Sepideh, Sahab-Negah, Sajad, Gorji, Ali
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Biochemistry
Biomedical Engineering and Bioengineering
Brain cancer
Brain tumor
Cancer
Cancer Research
Chemistry and Materials Science
Controlled release
Materials Science
Metastasis
Nanoparticles
Nanotechnology
Reactive oxygen species
Scaffold
Stem cells
Toxicity
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Summary:Despite advances in glioblastoma (GBM) treatments, current approaches have failed to improve the overall survival of patients. The oncogene BMI-1, a core member of the polycomb group proteins, is a potential novel therapeutic target for GBM. To enhance the efficacy and reduce the toxicity, PTC209, a BMI-1 inhibitor, was loaded into a PLGA–PEG nanoparticle conjugated with CD133 antibody (Nano-PTC209) and its effect on the behavior of human GBM stem-like cells (GSCs) and the human glioblastoma cell line (U87MG) was assessed. Nano-PTC209 has a diameter of ~ 75 nm with efficient drug loading and controlled release. The IC50 values of Nano-PTC209 for GSCs and U87MG cells were considerably lower than PTC209. Nano-PTC209 significantly decreased the viability of both GSCs and U87MG cells in a dose-dependent manner and caused a significant enhancement of apoptosis and p53 levels as well as inhibition of AKT and JNK signaling pathways. Furthermore, Nano-PTC209 significantly inhibited the migration ability, decreased the activity of metalloproteinase-2 and -9, and increased the generation of reactive oxygen species in both GSCs and U87MG cells. Our data indicate that PLGA–PEG nanoparticle conjugated with CD133 antibody could be an ideal nanocarrier to deliver PTC209 and effectively target BMI-1 for potential approaches in the treatment of GBM.
ISSN:1868-6958
1868-6966
DOI:10.1186/s12645-021-00078-8