Targeted drug delivery using Graphene Quantum Dots – Approaches, limitations, and future perspectives.

Abstract

Graphene is a type of single-layered two-dimensional nanomaterial, becoming increasingly recognized by the scientific community owing to its considerable unique properties, both in terms of physical and chemical characteristics. These include high surface area, mechanical strength, low toxicity, and ease of functionalization, just to name a few. Graphene Quantum Dots (GQDs), the zero-dimensional nanomaterials, are the derivatives of graphene inheriting the majority of superior properties of graphene, and have been broadly investigated for a diversity of applications. Additionally, with the presence of –COOH and other functional groups on the surface of GQDs, numerous molecules can be linked via chemical bonds. Moreover, GQDs being environmentally friendly due to its non-toxic and biologically inert properties have gained significant interest in biomedical industry. The full potential of GQDs in the field of therapeutics and nanomedicine is only nearing its maximum level. Recent developments in nanobiotechnology have seen GQDs at the forefront of third-generation drug therapies and other applications. This mini-review centers on the framework of GQDs to function as a Drug Delivery System (DDS) that is both target-specific and efficient. Researchers exploit GQDs for the unique pharmacokinetic properties they possess, that make them an ideal multi-functional drug delivery vehicle.
We cannot enhance the therapeutic efficacy of drugs merely by focusing on drug delivery mechanisms. The conjugation of the drug with GQD allows more flexibility in controlling the kinetics and duration of stay of the drug (circulation time) in the body, the characteristic which is highly regarded in modern therapeutics. GQDs offer a wide range of advantages over other nanomaterials, such as enhanced water solubility, lower cytotoxicity, tunable photoluminescence properties, larger specific surface area, large surface to volume ratio, and ease of surface functionalization. These properties make them highly effective drug molecular loading cores [1]. Therefore, they are more suitable to deliver anti-tumour drugs to target cancer cells.
Also, the review addresses the various methods of synthesis of GQDs that include top-down approach (chemical oxidation, hydrothermal method, ultrasonic-assisted method, etc.) and bottom-up processes (microwave method, molecular carbonization and electron beam irradiation). Top-down approaches are more feasible and advantageous.
The review touches on the various modes of GQD drug-loaded delivery-release systems (DDRS). The release of drugs at target tissues depends on certain properties like enhanced permeability and retention, excess number of complementary receptors to specific ligands, and acidic environment of the tissues. The properties of GQDs allow researchers to design a drug delivery system (DDS) that gives them control over the dynamics of the drug [2].
According to the need for therapy and the targeted site (or cells) of the drug, GQD-based drug delivery system (GQD-DDS) follow different approaches. Each approach seeks to gain an edge over the administration of the free drug alone. Modification of GQDs by functionalisation makes it possible to design carriers more suitable for multiple approaches. GQDs allow the release of drugs at cell compartments at specific pH ranges. Also, it can carry ligands that are specific to over-expressed receptors on the drug targeted cells. The site-specific approach reduces the potential risk to healthy cells, therefore, minimizing systemic toxicity [3].
The carrier has a high surface to volume ratio that improves the loading capacity and offers a sustained release of the drug. This boosts the bioavailability and therapeutic effect of the drug. GQDs are relatively new to the Nano-oncology area. The combination of GQD-DDS with biochemical ligands like IgG, complement factors, promotes the phagocytosis of cancer cells. It facilitates drug cytotoxicity and cell permeability in cancer cells. The flexible attributes of the GQD-DDS enhance the activity of the loaded drug and keep the drug protected from physiological factors [4].
The review also addresses the limitations associated with drug delivery using GQDs. The small size and surface charge of the GQD-DDS affect the internalisation process of nanoparticles into the cell. Insufficient information about the translocation of GQDs limits the application of their use in the biomedical field. The biodegradability and removal of the carrier after the drug reaches the target, is still under investigation [5]. A combination of such factors makes it difficult for GQD based carriers to pass clinical trials. The discovery and isolation of GQDs are quite recent, making it a hot and intriguing domain of research. The above-mentioned limitations may be considered as challenges, which can be overcome eventually by devising effective strategies for fabrication of nano-drug conjugates. Technological advancements allow the fast progress of research involved in GQDs. GQDs has now entered fields like gene delivery, long-acting drug delivery, Nano-neurology (due to their ability to cross the blood-brain barrier), and anti-inflammatory therapy. Furthermore, they find potential applications in diagnostics for the detection of biomarkers, and precision medicine technology (cellular level targeting) [6].
Through this review, we look to summarize the important concept of drug delivery using GQDs and their biomedical applications and scope in nanomedicine in foreseeable future. Figure 1 outlines the various modes of synthesis of GQDs, the potential applications of the nanoparticle, mechanisms or approaches for targeted drug delivery using GQD-DDS, and the future prospects of this nano-drug delivery system.
We also look to provide our take on the future of such an exhilarating scientific discovery that has the potential to enhance the life expectancy of patients diagnosed with lethal diseases.