Facile Synthesis of N-Doped Graphene Quantum Dots as Novel Transfection Agents for mRNA and pDNA

Abstract

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, global pharmaceutical companies have developed vaccines for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Some have adopted lipid nanoparticles (LNPs) or viral vectors to deliver the genes associated with the spike protein of SARS-CoV-2 for vaccination. This strategy of vaccination by delivering genes to express viral proteins has been successfully applied to the mRNA vaccines for COVID-19, and is also applicable to gene therapy. However, conventional transfection agents such as LNPs and viral vectors are not yet sufficient to satisfy the levels of safety, stability, and efficiency required for the clinical applications of gene therapy. In this study, we synthesized N-doped graphene quantum dots (NGQDs) for the transfection of various genes, including messenger ribonucleic acids (mRNAs) and plasmid deoxyribonucleic acids (pDNAs). The positively charged NGQDs successfully formed electrostatic complexes with negatively charged mRNAs and pDNAs, and resulted in the efficient delivery and transfection of the genes into target cells. The transfection efficiency of NGQDs is found to be comparable to that of commercially available LNPs. Considering their outstanding stability even at room temperature as well as their low toxicity, NGQDs are expected to be novel universal gene delivery platforms that can outperform LNPs and viral vectors.

A Historical Review of Brain Drug Delivery

“…Graphene oxide quantum dots are spherical structures with a diameter of about 10 nm [859]. GO carbon dots were conjugated to glucose to facilitate CMT across the BBB on the GLUT1 glucose carrier [860].…”

One-Step Colloidal Synthesis of Non-Toxic Electroactive Carbon Dots with a Better Threshold Cytotoxicity and Cytocompatibility

“…An increase in a concentration above the threshold concentration (50 μg/mL) relatively decreases the cellular viability down to 60% at 100 μg/mL . Ahn et al also reconfirmed that the size of the nanodots or QDs plays a crucial role in cytotoxicity …”

“…45 Ahn et al also reconfirmed that the size of the nanodots or QDs plays a crucial role in cytotoxicity. 43 Another important parameter is surface functionalization, which critically depends on the synthesis approaches. For example, Yu et al developed gadolinium-doped CDs emitting a blue PL with a low cellular cytotoxicity, with the potential for dual-modal fluorescence or MR imaging.…”

Bioactive Graphene Quantum Dots Based Polymer Composite for Biomedical Applications

“…The application of bioactive GQD-based polymer composite on other non-viral vectors seems to be less common than using bioactive GQD-based polymer composites as drug delivery agents. Due to the sp2 hybridized structure and π-stacking in bioactive GQDs-based polymer composite systems, the possibility of drug loading in bioactive GQD-based polymer composite systems is higher than in other nanoparticle-based drug delivery systems [ 252 , 253 , 254 , 255 , 256 ].…”