Chiral Graphene Quantum Dots Enhanced Drug Loading into Small Extracellular Vesicles

As nanoscale extracellular vesicles secreted by cells, small extracellular vesicles (sEVs) have enormous potential as safe and effective vehicles to deliver drugs into lesion locations. Despite promising advances with sEV-based drug delivery systems, there are still challenges to drug loading into sEVs, which hinder the clinical applications of sEVs. Herein, we report an exogenous drug -agnostic chiral graphene quantum dots (GQDs) sEV-loading platform, based on chirality matching with the sEV lipid bilayer. Both hydrophobic and hydrophilic chemical and biological drugs can be functionalized or adsorbed onto GQDs by pi-pi stacking and van der Waals interactions. By tuning the ligands and GQD size to optimize its chirality, we demonstrate drug loading efficiency of 66.3% and 64.1% for doxorubicin and siRNA, which is significantly higher than other reported sEV loading techniques.

Automated summary

As nanoscale extracellular vesicles secreted by cells, small extracellular vesicles (sEVs) have great potential as safe and effective drug delivery vehicles. However, there are challenges in loading drugs into sEVs, which hinders their clinical applications. This study presents an exogenous drug-agnostic chiral graphene quantum dots (GQDs) sEV-loading platform, which can efficiently load both hydrophobic and hydrophilic drugs onto GQDs through pi-pi stacking and van der Waals interactions. By optimizing the chirality of the ligands and GQDs, the drug loading efficiency for doxorubicin and siRNA is significantly higher compared to other reported sEV loading techniques.