Designing and testing a molecularly targeted glioblastoma theranostic: experimental and computational studies

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Getachew Ebuy Tedla (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Christopher Kepley

Abstract: With an extremely poor patient prognosis glioblastoma multiforme (GBM) is one of the most aggressive forms of brain tumor with a median patient survival of less than 15 months. While new diagnostic and therapeutic approaches continue to emerge, the progress to reduce the mortality associated with the disease is insufficient. Thus, developing new methods having the potential to overcome problems that limit effective imaging and therapeutic efficacy in GBM is still a critical need. The overall goal of this research was therefore to develop targeted glioblastoma theranostics capable of imaging disease progression and simultaneously killing cancer cells. To achieve this, the state of the art of liposome based cancer theranostics are reviewed in detail and potential glioblastoma biomarkers for theranostic delivery are identified by querying different databases and by reviewing the literature. Then tumor targeting liposomes loaded with Gd3N@C80 and doxorubicin (DXR) are developed and tested in vitro. Finally, the stability of these formulations in different physiological salt solutions is evaluated using computational techniques including area per lipid, lipid interdigitaion, carbon-deuterium order parameter, radial distribution of ions as well as steered molecular dynamic simulations. In conclusion the experimental and computational studies of this dissertation demonstrated that DXR and Gd3N@C80-OH loaded and lactoferrin & transferrin dual-tagged, PEGylated liposomes might be potential drug and imaging agent delivery systems for GBM treatment.

Designing and testing a molecularly targeted glioblastoma theranostic: experimental and computational studies
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Created on 12/1/2018
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Additional Information

Publication
Dissertation
Language: English
Date: 2018
Keywords
Gd3N@C80, Glioblastoma, Lipid bilayer, Molecular dynamics, Theranostics, Transferrin & lactoferrin
Subjects
Glioblastoma multiforme $x Treatment
Molecular dynamics
Bilayer lipid membranes
Doxorubicin $x Therapeutic use
Lactoferrin
Transferrin

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This item contains the following parts:

TitleLocation & LinkType of Relationship
Browinian Motion Liposomeshttp://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_1_Browinian_ Motion_Liposomes.aviThe described resource includes the related resource either physically or logically.
C80 in KCl non SMDhttp://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_2_C80_in_KCl_non_SMD.mp4The described resource includes the related resource either physically or logically.
With Water Non SMD 2http://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_4 _C80_in_CaCl2_with_water_non_SMD_2.mp4The described resource includes the related resource either physically or logically.
No Water Non SMDhttp://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_3_C80-OH42_in_KCl_no_water_non_SMD.mp4The described resource includes the related resource either physically or logically.
SI 5http://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_5.mp4The described resource includes the related resource either physically or logically.
LIG CaCl2 SMD 2http://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_6_LIG_CaCl2_SMD_2.mp4The described resource includes the related resource either physically or logically.
UNL SMD 2http://libres.uncg.edu/ir/uncg/f/Tedla_uncg_0154D_12622_SI_7_UNL_SMD_2.mp4The described resource includes the related resource either physically or logically.