Design of peptide functionalized nitrogen doped graphene quantum dots for theranostic application in breast cancer

The nitrogen doped graphene quantum dots (N-GQDs) were functionalized for active targeting of epidermal growth factor receptor (EGFR) overexpressed breast cancer cells for the delivery of palbociclib (PLB). The N-GQDs were covalently conjugated with a dodecapeptide, GE11 (YHWYGYTPQNVI), a ligand with high affinity for EGFR and then loaded with PLB. The resulting PLB loaded N-GQDs (PLB-N-GQDs) and GE11-N-GQDs (GE11-PLB-N-GQDs) exhibited particle size of 85.25 ± 1.65 nm and 115.1 ± 2.47 nm, respectively. The surface functionalization of GE11 was confirmed by amide bond formation. The high-resolution transmission electron microscopy study revealed structural distortion in the GE11-PLB-N-GQDs due to functionalization and drug loading. The formulations were hemocompatible and hence were suitable for direct administration. The GE11-PLB-N-GQDs showed significantly higher release at pH 5.5 than pH 6.8 and pH 7.4. The confocal microscopy displayed the use of inherent fluorescence of the N-GQDs and GE11-N-GQDs across MCF-7 cells indicating their potential for bioimaging. The increased cellular uptake of the GE11-N-GQDs demonstrated effective EGFR targeting which increased cytotoxicity by the GE11-PLB-N-GQDs as compared to the PLB-N-GQDs. The GE11-PLB-N-GQDs induced G1 phase cell cycle arrest and apoptosis. This study demonstrates the potential of GE11-N-GQDs as a versatile theranostic nanocarrier for targeted delivery to breast cancer cells overexpressing EGFR.