Exploiting Endocytosis for Non-Spherical Nanoparticle Cellular Uptake

Several challenges exist for successful nanoparticle cellular uptake—they must be able to cross many physical barriers to reach their target and overcome the cell membrane. A strategy to overcome this challenge is to exploit natural uptake mechanisms namely passive and endocytic (i.e., clathrin- and caveolin-dependent/-independent endocytosis, macropinocytosis and phagocytosis). The influence of nanoparticle material and size is well documented and understood compared to the influence of nanomaterial shape. Generally, nanoparticle shape is referred to as being either spherical or non-spherical and is known to be an important factor in many processes. Nanoparticle shape-dependent effects in areas such as immune response, cancer drug delivery, theranostics and overall implications for nanomedicines are of great interest. Studies have looked at the cellular uptake of spherical NPs, however, fewer in comparison have investigated the cellular uptake of non-spherical NPs. This review explores the exploitation of endocytic pathways for mainly inorganic non-spherical (shapes of focus include rod, triangular, star-shaped and nanospiked) nanoparticles cellular uptake. The role of mathematical modelling as predictive tools for non-spherical nanoparticle cellular uptake is also reviewed. Both quantitative structure-activity relationship (QSAR) and continuum membrane modelling have been used to gain greater insight into the cellular uptake of complex non-spherical NPs at a greater depth difficult to achieve using experimental methods.