Unraveling Framework Nucleic Acid–Skin Cell Interactions with a Co-Culture System

Framework nucleic acid (FNA) is an emerging drug carrier platform, with its biodegradability and uniform, tunable structures. Recently, its applicability in transdermal drug delivery has been demonstrated, extending the range of applications that are predominantly based on intravenous injection. However, FNA's interaction and impact toward the skin cells are yet to be elucidated. This study employs an optically clear keratinocyte/fibroblast co-culture system to visualize the FNA–skin cell interactions. FNA's influence on these cells is evaluated through polymerase chain reaction analyses and metabolism assays. A size-dependent interaction and cellular internalization on both keratinocytes and fibroblasts is observed, with no adverse effects on cell viability and functions.