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GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)

Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific delivery of active...

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Detalles Bibliográficos
Autores principales: Velpurisiva, Praveena, Piel, Brandon P., Lepine, Jack, Rai, Prakash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315921/
https://www.ncbi.nlm.nih.gov/pubmed/30304810
http://dx.doi.org/10.3390/bioengineering5040083
Descripción
Sumario:Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific delivery of active pharmaceutical ingredients and facilitates entrapment inside the tumor. Polo-like kinase 1 (PLK-1) inhibitors have shown promising results in tumor cells. GSK461364A (GSK) is one such targeted inhibitor with reported toxicity issues in phase 1 clinical trials. We have demonstrated in our study that the action of GSK is time dependent across all concentrations. There is a distinct 15−20% decrease in cell viability via apoptosis in U87-MG cells dosed with GSK at low concentrations (within the nanomolar and lower micromolar range) compared to higher concentrations of the drug. Additionally, we have confirmed that PLGA-PEG nanoparticles (NPs) containing GSK have shown significant reduction in cell viability of tumor cells compared to their free equivalents. Thus, this polymeric nanoconstruct encapsulating GSK can be effective even at low concentrations and could improve the effectiveness of the drug while reducing side effects at the lower effective dose. This is the first study to report a PLK-1 inhibitor (GSK) encapsulated in a nanocarrier for cancer applications.