Exploration of RGD peptide-modified targeted delivery of doxorubicin using chitosan oligosaccharide-coated GQD carriers with different complexity

Cancer therapy is often limited by suboptimal tumor targeting and systemic toxicity. To address these challenges, a pre-modified drug with targeting ligands, such as the RGD-4C peptide, has emerged as a potential strategy. However, pre-modified doxorubicin (RGD-DOX) alters traditional interactions among the drug, delivery systems, and cancer cells. In this study, we investigated two graphene quantum dot (GQD)-based carriers with distinct complexities for delivering RGD-DOX. The first carrier, PEGylated GQDs with gold nanoparticles (APG), leveraged enhanced colloidal stability and multifunctionality, while the second, a chitosan oligosaccharide-coated GQD (CG), offered charge-based encapsulation and biodegradability. Both carriers effectively encapsulated RGD-modified DOX, demonstrating pH-responsive drug release triggered by the acidic tumor microenvironment. In vitro studies revealed that RGD-DOX delivered by both carriers induced significant cellular apoptosis through mechanisms similar to unmodified DOX, as evidenced by DNA damage and apoptotic markers. In vivo experiments further verified effective tumor suppression with less loaded DOX medicine, which could minimize systemic toxicity. These findings validate the potential of an RGD-pre-modified DOX based on one step assembly-GQD drug delivery systems, demonstrating high targeting efficiency with reduced potential side effects, and presenting a novel strategy for drug delivery system design.