Peptide conjugated nintedanib loaded graphene quantum dots: Characterization and cell based studies

The present study is aimed to develop the nitrogen doped graphene quantum dots (N-GQDs) based nanocarrier to target epidermal growth factor receptor (EGFR) in the treatment of non-small cell lung cancer (NSCLC). The N-GQDs were functionalized with GE11 peptide (a targeting agent) with high affinity for EGFR (GE11-N-GQDs), using carbodiimide chemistry. The studies revealed that the particle size of the N-GQDs increased to 96.88 ± 2.16 nm after NE loading (NE-N-GQDs). The GE11 functionalization and NE loading (GE11-NE-N-GQDs) further increased the particle size to 124.0 ± 1.76 nm. The particle shape of the GE11-NE-N-GQDs were cubic and quasi-hexagonal. The reduction in the crystallinity was evident by the selected area electron diffraction (SAED) pattern. The GE11-NE-N-GQDs showed higher drug loading (97.42 ± 1.15 %) and entrapment efficiency (98.14 ± 1.32 %) than the NE-N-GQDs (97.38 ± 1.46 %, 92.36 ± 1.68 %). The N-GQDs based nanocarriers displayed good antioxidant activity and hemocompatibility. The GE11-NE-N-GQDs displayed pH dependent and prolonged release (99.78 ± 2.20 %) at 50 h. The %cell viability of the GE11-NE-N-GQDs treated A549 (human lung adenocarcinoma) cells was less (IC₅₀: 1 µg/ml) than the NE-N-GQDs (IC₅₀: 3 µg/ml) and free NE (IC₅₀: 6.60 µg/ml). The GE11-N-GQDs enhanced intracellular uptake and arrested G1 phase which increased apoptosis and number of cells in sub-G1 phase. Hence, the results showed the GE11-N-GQDs as a promising approach to target EGFR overexpression in NSCLC.