Design maps for cellular uptake of gene nanovectors by computer simulation

Understanding how nanovectors transport DNA molecules through cell membranes is of great importance in gene therapy. In this paper, we systematically investigate the mechanism of cellular uptake of cationic polymeric nanovectors containing DNA molecules through dissipative particle dynamics simulations. Our results show that the property of polyelectrolyte chains grafted to nanovector and DNA molecules can have important impacts on the endocytosis. Interestingly, it is found that the nanovector can be fully taken up with proper number of DNA molecules on its surface. On the contrary, in the absence of DNA it may become harder to be totally engulfed. Since the adsorption number of DNA is related to external pH, the cellular uptake could exhibit pH-responsive behavior. Further, we also provide insights into the comparison of uptake behaviors between cancer and normal cells, and importantly, we find that the enhanced uptake of gene nanovectors may be an inherent property of cancer cells. The present study may give some significant suggestions on future nanovector design for gene delivery.