Influence of surface charge of graphene quantum dots on their uptake and clearance in melanoma cells.

Graphene quantum dots (GQDs) continue to draw interest in biomedical applications. However, their efficacy gets compromised due to their rapid clearance from the body. On one hand, rapid clearance is desired and considered advantageous in terms of their cytocompatibility, but on the other hand, it is a major limitation for their prolonged use as imaging and therapeutic probes. The uptake and clearance of GQDs have been described , however, their clearance is still not understood, one of the main reasons being that their uptake and clearance are a cell type-dependent phenomena. Studies on other types of quantum dots revealed the importance of surface charge in their uptake and retention in different cell types. However, the role of surface chemistry in GQD uptake and clearance has not been described previously. Here, we studied the influence of surface charge on GQDs (anionic and cationic) on their uptake and clearance in melanoma cells. Both cationic and anionic GQDs were synthesized using a hydrothermal method to have a relatively consistent size with an aim to study the role of surface charge in their uptake and clearance in isolation by avoiding size-dependent uptake bias. Both GQDs exhibited excellent biocompatibility with cell viability over 90% even at a high concentration of 200 μg mL. Using confocal microscopy and flow cytometry, we observed significantly faster and higher uptake of cationic GQDs compared to anionic GQDs. Consequently, relatively rapid clearance was observed in cells treated with anionic GQDs compared to those treated with cationic GQDs, highlighting the role of surface charge on GQDs in their uptake and clearance. Raman analysis of the cleared exocytosed GQDs revealed no sign of biodegradation of either type.