Role of charge in enhanced nuclear transport and retention of graphene quantum dots

AbstractThe nuclear pore complexes on the nuclear membrane function as the sole gateway of molecular communication between the nucleus and the cytoplasm regulating the transport of molecules, including nucleic acids and proteins. The present study seeks to undertake a comprehensive investigation of the kinetics of transport of negatively charged graphene quantum dots through nuclear membranes and quantify their nuclear transport characteristics and translocation rates. Experiments are carried out in permeabilized HeLa cells using time-lapse confocal fluorescence microscopy. Introducing negative charge onto biomolecular probes leads to electrostatic interaction with the nuclear pore complexes resulting in significant changes in their nuclear translocation rates. We find that the negatively charged graphene quantum dots are transported to the nuclei at a fast rate and two distinct transport pathways are involved in the translocation. Furthermore, complementary experiments on the nuclear import and export of these graphene quantum dots confirm the bidirectionality of transport with similar translocation rates. Our studies also show that negatively charged graphene quantum dots exhibit good retention properties revealing their potential as excellent drug carriers.Statement of significanceThe nuclear pore complexes control the bidirectional transport of biomolecules between the nucleus and cytoplasm. The noteworthy behaviors exhibited by negatively charged graphene quantum dots with respect to the nuclear uptake show their potential utility not only as drug carriers but also as facilitators for the retention of drugs within the nucleus. The fast import of carriers helps to achieve faster drug delivery, and the retention ensures the passing of the drug to daughter nuclei.Graphical abstract