The Investigation of the Uptake of Interleukin-13 Conjugated Nanoparticles into Glioma Cells

Open Access
Author:
Porter, Michael John
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Sheereen Majd, Thesis Supervisor
  • William O Hancock, Honors Advisor
  • Herbert Herling Lipowsky, Faculty Reader
Keywords:
  • Nanoparticle
  • Nanoparticles
  • IL-13
  • Interleukin
  • Glioma
  • GBM
  • Glioblastoma multiforme
  • conjugated
  • computational
  • kinetics
Abstract:
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor and presents the worst prognosis. However, despite the use of combined treatments of chemotherapy, radiation treatment, and surgical oncology, the median survival time of 1 year for a brain cancer patient has not significantly improved in the past three decades. For this reason, novel treatments are needed to improve clinical outcomes of GBM. The focus of this study is to construct a more effective method for delivering chemotherapy drugs to glioma cells. To this end, the present study takes advantage of the selective affinity of nanoparticles conjugated with ligands whose receptors are known to be overexpressed in glioma cells compared to normal neuroglia. It has been shown that various glioma cell lines express significantly higher levels of interleukin-13 receptor (IL-13) than normal glial cells. Therefore, the conjugation of IL-13 to nanoparticle encapsulated drugs is hypothesized to increase cellular uptake. Using fluorescence microscopy of tissue culture cells, glioma cells were shown to uptake PLGA nanoparticles conjugated with IL-13 at a higher rate than unconjugated PLGA nanoparticles In parallel with the experimental investigation of nanoparticle uptake into glioma cells, the kinetics of receptor-mediated endocytosis of IL-13 PLGA nanoparticles was studied computationally. Modeling of nanoparticle endocytosis was accomplished via a system of ODEs derived from the law of mass action. Computational rate constants were determined in an iterative process to ascertain an appropriate fit for the experimental investigation. The computational model provided a good fit to the experimental results and was consistent with the conjugation of IL-13 to PLGA nanoparticles enhancing the rate of nanoparticle endocytosis. A more comprehensive kinetic model can be established from studies into the elementary reactions that govern endocytosis for nanoparticles. Further research in this area may benefit the development of nanoparticle drug carriers.