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

Abstract

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.