Optimizing design for carbon nanotubes as gene delivery carriers: A computer study

Understanding the interaction mechanisms between carbon nanotubes (CNTs) and lipid membranes is crucial for advancing drug/gene delivery technologies. However, design principles for CNTs as drugs/genes with efficient transmembrane transport ability are still lacking. In this work, we used molecular dynamics (MD) simulations to systematically investigate the transmembrane mechanism for different properties of CNTs with varying aspect ratios, surface properties (including helical, striped, and hydrophobic modifications), single-walled carbon nanotubes (SWNTs), multi-walled carbon nanotubes (MWNTs) and the concentration of CNTs. Our results show that when either CNT length or diameter is smaller than the membrane thickness, they exhibit better membrane penetration and lower cytotoxicity. The initial angle of the CNT has little impact on its penetration ability. Surface modifications significantly affect the penetration process. Hydrophobic CNTs achieve the highest penetration efficiency, while striped modifications improve solubility and facilitate better membrane penetration compared to helical modifications. We also find that CNTs at higher concentrations tend to induce more significant cytotoxicity. Furthermore, loading genes inside CNT improves membrane penetration and reduces cytotoxicity, providing a safer and more efficient delivery method than outside loading. These findings highlight the importance of optimizing CNT properties such as aspect ratio, surface modification, and concentration to achieve safe and efficient transmembrane delivery, which guides the design of CNT for gene/drug delivery.