Carbon dot-based polyplexes with cell penetration peptides for gene transfection

This study explores the synthesis, characterization, and gene-delivery efficacy of polyplexes comprising carbon nanomaterials, namely, graphene oxide quantum dots (GO QDs) and carbon dots (CDs), in conjunction with cell-penetrating peptides (CPPs), namely, PF14 or PF221, alongside gene therapeutic agents (pGL3 plasmids or splice-correcting oligonucleotides (SCO)). GO QDs were created using Hummers' method, followed by acid fragmentation, while CDs were generated by an eco-friendly solvothermal procedure utilizing ascorbic acid as a precursor. Structural and morphological characterization using X-ray diffraction (XRD), transmission electron microscopy (TEM), and zeta potential analysis confirmed the synthesis of nanocomplexes with distinct physicochemical properties. Gene transfection assays demonstrated that PF14-CD polyplexes attained superior efficiency in delivering pGL3 and SCO, surpassing GO QDs and PF221-based methods. Mechanistic studies revealed that the cellular uptake of PF14-SCO-CDs is predominantly mediated by scavenger receptor class A (SCARA), as evidenced by the significant inhibition observed with SCARA-specific inhibitors. The use of PF14 and CDs presents a promising model for efficient gene transport, primarily governed by receptor-mediated endocytosis.