Graphene Quantum Dots as Intracellular Calcium Influx Regulators

Calcium ion (Ca²⁺) is a key factor involved in the function of nearly all cells. The Ca²⁺ signaling system affects a variety of cellular processes. It is well known that abnormal Ca²⁺ level disrupts the dynamic range of cellular signaling and causes various major diseases, including Alzheimer's disease, heart disease, and hypertension. Therefore, regulating intracellular calcium influx is a promising therapeutic strategy for these diseases.
The administration of calcium-binding agents that directly bind to Ca²⁺ within cells can be an effective method to fundamentally eliminate cytosolic calcium overload. Previous studies have shown that calcium chelators, such as 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), suppress oxidative stress in cells and reduces the rate of cell death, showing therapeutic effects in acute liver failure, acute pancreatitis, and acute kidney injury. Thus, discovering materials with both high biocompatibility and calcium-binding capacity can be an important strategy in developing new therapeutics.
Graphene quantum dots (GQDs) are new zero-dimensional materials composed of a graphene core and abundant edge functional groups. The low toxicity and high solubility derived from these structures offer significant advantages for the application of GQDs in the biomedical field such as biosensor, bioimaging and drug delivery. Recent studies highlight the therapeutic properties of GQDs for various incurable diseases like Parkinson's disease. Several studies have reported that the therapeutic abilities of GQDs may stem from regulation of intracellular calcium influx. However, there is a lack of research focused on the nature of GQDs that directly involve calcium-binding capability.
Here, we investigate the key characteristics of GQDs involved in calcium interactions. The photoluminescence (PL) study demonstrated that interactions with calcium induce PL quenching of GQDs. The zeta potential results indicated that GQDs possess a surface negative charge, showing dispersion stability in a pH 7 solution, which suggests electrostatic interactions with positively charged calcium ions. Additionally, it was confirmed that GQDs exhibit calcium-mediated aggregation behavior in solutions. Studies on the calcium binding mechanism indicated that specific oxygen functional groups present on the surface of GQDs are involved in calcium binding. Finally, batch calcium absorption studies demonstrated that GQDs could remove free calcium from the solution. Our results suggest the potential of GQDs as promising biocompatible calcium binding agents for intracellular calcium influx regulators.