TitleMultimodal nanoparticle-based platforms for cancer therapy
NameJung, Jongjin (author), Lee, Ki-Bum (chair), Li, Jing (internal member), Asefa, Tewodros (internal member), Fabris, Laura (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectChemistry and Chemical Biology,
DescriptionNanoscience has attracted attention as a fast burgeoning field with promising methodologies for cancer diagnosis and therapy. We designed target-specific nanoparticle -based platforms to induce the apoptosis of human brain cancer cells and to show their capability for in vivo theragnostics which combines therapy and diagnosis. Quantum Dot (QD)-based system was demonstrated to deliver siRNA and monitor its uptake using extremely bright fluorescence of QDs. siRNA-QDs against GFP not only showed increased efficiency of transfection, but also synchronized QDs’ color and their localization. As a model study, glioblastoma multiforme (GBM) was chosen because of high malignancy and invasiveness resulting in short mean survival rate. Multiplexing with integrin-targeting RGD and TAT peptide enabled siRNA-QDs to be delivered specifically to U87 cells, a GBM cell line with highly expressed integrin. As a chemotheragnostic agent, siRNA-QDs were transfected into GBM cells that overexpress epidemic growth factor receptor variant III (EGFRvIII). Efficiently delivered siRNA-QDs against EGFRvIII led to abnormal cell morphology and decreased cell population. These were caused by successful knockdown of EGFRvIII gene and resulting silencing of the PI3K/AKT signaling pathway, which plays an important role in cancer proliferation and apoptosis. In spite of high potential of siRNA-QD system, cytotoxicity and skin depth issues lead to the development of a magnetic nanoparticle (MNP)-based theragnostic system for in vivo application. Graphite-coated FeCo MNPs (FeCo/C) exhibited superparamagnetic properties with high crystallinity and magnetization. In addition, Raman imaging is made possible by graphite shell designed for protection of FeCo core from decomposition and oxidation. Compared to conventional iron oxide MNPs, FeCo/C showed much higher T2-weighted magnetic resonance contrast. Dextrans were also developed to stabilize FeCo/C in physiological condition as well as to conjugate therapeutic or targeting molecules such as siRNA, antibody, and cyclic RGD. High magnetization of FeCo/C allowed for target-specific hyperthermia against U87 cells by local heating under AC magnetic field. Additionally, siRNA-FeCo/C against EGFRvIII followed by hyperthermia synergistically induced significant cell death of U87-EGFRvIII, which proved that the target-specific siRNA-FeCo/C system is a promising candidate for in vivo theragnostic agent.
NoteIncludes bibliographical references
Noteby Jongjin Jung
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.