Cancer therapeutic siRNA delivery and imaging by nitrogen- and neodymium-doped graphene quantum dots

• Verfasst von: Valimukhametova, Alina R. [VerfasserIn]
• Verfasst von: Lee, Bong Han [VerfasserIn]
• Verfasst von: Topkiran, Ugur C. [VerfasserIn]
• Verfasst von: Gries, Klara [VerfasserIn]
• Verfasst von: Gonzalez-Rodriguez, Roberto Hernan [VerfasserIn]
• Verfasst von: Coffer, Jeffery [VerfasserIn]
• Verfasst von: Akkaraju, Giridhar [VerfasserIn]
• Verfasst von: Naumov, Anton [VerfasserIn]
• Titel: Cancer therapeutic siRNA delivery and imaging by nitrogen- and neodymium-doped graphene quantum dots
• Verf.angabe: Alina R. Valimukhametova, Bong Han Lee, Ugur C. Topkiran, Klara Gries, Roberto Gonzalez-Rodriguez, Jeffery L. Coffer, Giridhar Akkaraju, and Anton Naumov
• E-Jahr: 2023
• Jahr: May 31, 2023
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 20.07.2023
• Titel Quelle: Enthalten in: American Chemical SocietyACS biomaterials science & engineering
• Ort Quelle: Washington, DC : ACS Publ., 2015
• Jahr Quelle: 2023
• Band/Heft Quelle: 9(2023), 6, Seite 3425-3434
• ISSN Quelle: 2373-9878
• DOI: doi:10.1021/acsbiomaterials.3c00369
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1853160946

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 the inability of the genes alone to cell transfection, 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 visible and near-infrared regions. 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, respectively) for the delivery of Kirsten rat sarcoma virus (KRAS) and epidermal growth factor receptor (EGFR) siRNA effective against a variety of cancer types. GQDs loaded with siRNA noncovalently facilitate successful siRNA transfection into HeLa cells, confirmed by confocal fluorescence microscopy at biocompatible GQD concentrations of 375 μg/mL. While the GQD 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 are 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 nontoxic delivery of siRNA and genes in general, complemented by multiwavelength image tracking.