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Velpurisiva P, Piel BP, Lepine J, et al. GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM). Bioengineering (Basel). 2018;5(4)doi: 10.3390/bioengineering5040083.
Velpurisiva, P., Piel, B. P., Lepine, J., & Rai, P. (2018). GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM). Bioengineering (Basel, Switzerland), 5(4), . https://doi.org/10.3390/bioengineering5040083
Velpurisiva, Praveena, et al. "GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)." Bioengineering (Basel, Switzerland) vol. 5,4 (2018). doi: https://doi.org/10.3390/bioengineering5040083
Velpurisiva P, Piel BP, Lepine J, Rai P. GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM). Bioengineering (Basel). 2018 Oct 09;5(4). doi: 10.3390/bioengineering5040083. PMID: 30304810; PMCID: PMC6315921.
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Bioengineering (Basel). 2018 Oct 09;5(4). doi: 10.3390/bioengineering5040083.

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

Bioengineering (Basel, Switzerland)

Praveena Velpurisiva, Brandon P Piel, Jack Lepine, Prakash Rai

Affiliations

  1. Department of Biomedical Engineering and Biotechnology, University of Massachusetts, Lowell, MA 01854, USA. [email protected].
  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. [email protected].
  3. Biomolecular Characterization Lab, Core Research Facility, University of Massachusetts Lowell, Lowell, MA 01854, USA. [email protected].
  4. Department of Biomedical Engineering and Biotechnology, University of Massachusetts, Lowell, MA 01854, USA. [email protected].
  5. Department of Chemical Engineering, University of Massachusetts, Lowell, MA 01854, USA. [email protected].

PMID: 30304810 PMCID: PMC6315921 DOI: 10.3390/bioengineering5040083

Abstract

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.

Keywords: GSK461364A; Glioblastoma Multiforme; U-87 MG; cytotoxicity; enhanced permeability and retention; oncology; oncomedicine; polo-like kinase inhibitor; polymeric nanoparticles

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