Cancer therapeutic siRNA delivery and imaging by nitrogen and neodymium-doped graphene quantum dotsShow full item record
Title | Cancer therapeutic siRNA delivery and imaging by nitrogen and neodymium-doped graphene quantum dots |
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Author | Valimukhametova, Alina |
Date | 2023-05-04 |
Genre | Thesis |
Abstract | While small interfering RNA (siRNA) technology has become a powerful tool that can enable cancer-specific gene therapy, its translation to the clinic is still hampered by several critical factors. These include the inability of cell transfection by the genes alone, poor siRNA stability in blood, and the lack of delivery tracking capabilities. Recently, graphene quantum dots (GQDs) have emerged as a novel platform allowing targeted drug delivery and fluorescence image-tracking in the visible and near-infrared. These capabilities can aid in overcoming primary obstacles to siRNA therapeutics. Here, for the first time, we utilize biocompatible nitrogen and neodymium-doped graphene quantum dots (NGQDs and Nd-NGQDs) for the delivery of Kirsten rat sarcoma virus (KRAS) and epidermal growth factor receptor (EGFR) siRNA effective against a variety of cancer types. The non-covalent loading of siRNA onto GQDs is evaluated and optimized by the electrophoretic mobility shift assay and zeta potential measurements. GQDs as a delivery platform facilitate successful gene transfection into HeLa cells confirmed by confocal fluorescence microscopy at biocompatible GQD concentrations of 375 µg/mL. While the NGQD platform provides visible fluorescence tracking, Nd doping enables deeper tissue near-infrared fluorescence imaging suitable for both in vitro and in vivo applications. The therapeutic efficacy of the GQD/siRNA complex is verified by successful protein knockdown in HeLa cells at nanomolar siEGFR and siKRAS concentrations. A range of GQD/siRNA loading ratios and payloads is tested to ultimately provide substantial inhibition of protein expression down to 31-45% comparable with conventional Lipofectamine-mediated delivery. This demonstrates the promising potential of GQDs for the non-toxic delivery of siRNA and genes in general, complemented by multiwavelength image-tracking. |
Link | https://repository.tcu.edu/handle/116099117/58268 |
Department | Physics and Astronomy |
Advisor | Naumov, Anton |
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- Masters Theses [4182]
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