GFP Plasmid and Chemoreagent Conjugated with Graphene Quantum Dots as a Novel Gene Delivery Platform for Colon Cancer Inhibition In Vitro and In Vivo

Abstract

Scientists have studied intensively the gene delivery carriers for treating genetic diseases. However, there are challenges that impede the application of naked gene-based therapy at the clinical level, such as quick elimination of the circulation, lack of membrane penetrability, and poor endosome trapping. Herein, we develop graphene quantum dots (GQDs)-derivative nanocarriers and introduce polyethylenimine (PEI) to equip the system with enhanced biocompatibility and abundant functional groups for modification. In addition to carrying green fluorescent protein (GFP) as an example of gene delivery, this system covalently binds colon cancer cells targeted antibody and epidermal growth factor receptor (EGFR) to enhance cell membrane penetrability and cell uptake of nanocarriers. To achieve multistrategy cancer therapy, the anticancer drug doxorubicin (Dox) is noncovalently encapsulated to achieve pH-induced drug release at tumor sites and leaves space for further functional gene modification. This nanoparticle serves as a multifunctional gene delivery system, which facilitates improved cytotoxicity and longer-sustained inhibition capacity compared to free Dox treatments in colon cancer cells. Moreover, our GQD composites display compatible tumor suppression ability compared with the free Dox treatment group in xenograft mice experiment with significantly less toxicity. This GQD nanoplatform was demonstrated as a multifunctional gene delivery system that could contribute to treating other genetic diseases in the future.

A pseudohomogeneous nanocarrier based on carbon quantum dots decorated with arginine as an efficient gene delivery vehicle

“…Presence of different functional groups on the surface with high density, special architecture and two-dimensional graphene network lead to endow excellent tendency of pseudohomogeneous carrier to bind with DNA. Besides, the DNA fragmentation does not occur due to no extra bonds of DNA are detected in gel electrophoresis proving that the proposed biocompatible nanocarrier meets the standards required to enter a clinical trials 5 , 6 , 39 , 42 , 43 .…”

“…The primary, secondary and tertiary amine groups are oriented toward the surface of CQDs and are protonated in different pH values. These amine groups are responsible for formation of complex with plasmid, interaction with cell membranes and capturing protons to accelerate early escape from endo/lysosomes 5 , 7 , 8 , 39 – 41 .…”

“…In this regard, the tendency of chitosan polymer and Arginine-CQDs to binding with plasmid, are investigated by gel retardation assay. Chitosan polymer with positive charge form complex with negatively charged DNA 10 – 13 , 39 . When the chitosan/plasmid weight ratio was 30:1 or 40:1, the plasmid bond was appeared on the gel, indicating that at these weight ratios, the interaction of the polymer with the plasmid did not result in a stable complex (Figs.…”

Recent advances in graphene quantum dot-based optical and electrochemical (bio)analytical sensors

“…GQDs can interact with different biological, inorganic, and organic molecules through electrostatic interactions and π-π conjugation, making them viable for fabricating the biosensing platforms 172 . Various biomolecules can be covalently immobilized to GQDs, preventing their…”

CuS/rGO-PEG Nanocomposites for Photothermal Bonding of PMMA-Based Plastic Lab-on-a-Chip

“…It can minimize damage to biological samples, because it generates the heat in a specific area by near-infrared (NIR) laser. Among photothermal nanomaterials, reduced graphene oxide (rGO) has widely been used in various research fields due to unique physiochemical properties [ 23 ]. However, since rGO has low solubility in aqueous solvents and has hydrophobic properties, its biological applications are limited, and it is also difficult to use for bonding to a hydrophobic substrate.…”