Edge‐Grafted Polyarginine Functionalization of Graphene Nanocarriers Maintains Noncovalent Aromatic Drug Loading

Covalent peptide grafting is widely used to improve the biological performance of nanocarriers, especially through cell-penetrating peptides (CPPs) that enhance cellular uptake. However, when drug loading relies on noncovalent interactions, peptide function￾alization may interfere with surface adsorption processes. This concern is particularly relevant for graphene-based nanocarriers, where π-conjugated molecules bind via π–π interactions on the basal plane. Here, we present an orthogonal functionalization strategy in which peptide conjugation occurs selectively at the edges of graphene nanoparticles (B60), which bear carboxylic acid groups, while π-conjugated cargo is adsorbed on the basal plane. Poly-arginine-11 (R11) was covalently immobilized, preserving the aromatic surface for π-π interactions. Using 1-pyrenecarboxylic acid and compound 8, a π-conjugated NEK6 inhibitor, we show that R11 grafting does not affect loading capacity or thermally induced release. Spectroscopic and microscopic analyses confirm that the basal plane remains intact and accessible after functionalization. Molecular dynamics simulations indicate that peptide chains form a flexible, charged corona at the nanoparticle periphery without perturbing molecule–graphene interactions. Overall, edge-grafted R11 preserves π-π-mediated loading and supports the design of peptide–graphene hybrid systems for deliv￾ering poorly soluble aromatic bioactive compounds.