Anchored but not internalized: shape dependent endocytosis of nanodiamond

Abstract

Nanoparticle-cell interactions begin with the cellular uptake of the nanoparticles, a process that eventually determines their cellular fate. In the present work, we show that the morphological features of nanodiamonds (NDs) affect both the anchoring and internalization stages of their endocytosis. While a prickly ND (with sharp edges/corners) has no trouble of anchoring onto the plasma membrane, it suffers from difficult internalization afterwards. In comparison, the internalization of a round ND (obtained by selective etching of the prickly ND) is not limited by its lower anchoring amount and presents a much higher endocytosis amount. Molecular dynamics simulation and continuum modelling results suggest that the observed difference in the anchoring of round and prickly NDs likely results from the reduced contact surface area with the cell membrane of the former, while the energy penalty associated with membrane curvature generation, which is lower for a round ND, may explain its higher probability of the subsequent internalization.

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“…Anisotropic gold nanoparticles with different shapes exhibited significant different cellular uptake (Xie et al, 2017). Similar results were also reported on other inorganic nanoparticles (Karaman et al, 2012;Dai et al, 2015), carbon nanotubes (Smith et al, 2012;Zhang et al, 2017), polymeric nanoparticles (Jurney et al, 2017), and folate nanocarriers (Tahmasbi Rad et al, 2019). Consistent with these findings, our result showed that LNSs obtained significantly enhanced cellular uptake and in vivo tumor extravasation ability compared with their spherical controls which shared the same length of lipid backbone.…”

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“…Furthermore, the smallest, isolated particles were observed to be free in the cytoplasm, when the bigger particles and aggregates were localized in the intracellular endocytic vesicles. Besides, the shape of a HPHT diamond nanoparticle appears to affect its internalization, trafficking inside the cell, and excretion from it [ 19 , 20 ]. Nevertheless, such behaviors are still debated in the scientific community.…”

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“…They explained that the curve shape of spherical particles allowed a limited number of their binding sites to interact with target cell receptors while the elongated nanoparticles had higher surface area, which facilitated the multivalent interaction of these particles with cell surface. Similarly, Zhang et al 109 mentioned that the prickly nanoparticles had a higher anchoring amount compared with the round nanoparticles. The results could be understood as originating from the contact surface area difference of the two types of nanoparticles with the plasma membrane.…”

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