Exocytosis - a putative road-block in nanoparticle and nanocomplex mediated gene delivery

Gene and drug delivery mediated by nanostructures has seen tremendous growth over the last decade. However, the efficiency of these delivery approaches needs to be improved for better effects. Amongst various factors, cellular retention is expected to play a critical role. Nanoparticles and nanocomplexes internalized by the cells can be recycled back to the outside through the process of exocytosis. Although it sounds reasonable that the efficiency of these delivery systems should not only depend on their cellular uptake but also on the ability of cells to retain them, the process of cellular retention and exocytosis is relatively less studied in the literature. In the context of gene delivery, both inorganic nanoparticles and organic nanocomplexes are used, but there is limited information on how these nanoparticles and nanocomplexes are recycled and what could be the possible effect of such recycling on the efficiency of these delivery vectors. In this review we try to summarize the existing literature in this area, putative mechanisms involved in recycling of the nanoparticles, methods used to quantify exocytosis and factors affecting exocytosis. The possibility of enhancing cellular retention by blocking recycling pathways as well as the in vivo implications is also discussed here.