In addition to a nanomaterial’s size, shape, and ligand density, surface charge is also important in
dictating cellular fate. Compared with nanoparticles with a neutral or negative charge, positively
charged nanoparticles are taken up at a faster rate (30, 31). It has been suggested that the cell
membrane possesses a slight negative charge and cell uptake is driven by electrostatic attractions
(17, 18). A recent study demonstrated that this electrostatic attraction between membrane and
positively charged nanoparticles favors adhesion onto the cell’s surface, leading to uptake. For
small nanoparticles (2 nm), a positive charge can perturb the cell membrane potential, causing
Ca2+ influx into cells and the inhibition of cell proliferation (32). For larger nanoparticles (4–
20 nm), surface charge induces the reconstruction of lipid bilayers (33). Binding of negatively
charged nanoparticles to a lipid bilayer causes local gelation, whereas binding of positively charged
nanoparticles induces fluidity. Several studies have confirmed the pivotal role surface charge plays
in downstream biological responses to nanoparticles. It is important to remember that, in the