Shape-Dependent Dissolution and Cellular Uptake of Silver Nanoparticles

Abstract

The cellular uptake and dissolution of trigonal silver nanoprisms (edge length 42 ± 15 nm, thickness 8 ± 1 nm) and mostly spherical silver nanoparticles (diameter 70 ± 25 nm) in human mesenchymal stem cells (hMSC's) and human keratinocytes (HaCaT cells) were investigated. Both particles are stabilized by polyvinylpyrrolidone (PVP), with the prisms additionally stabilized by citrate. The nanoprisms dissolved slightly in pure water but strongly in isotonic saline or at pH 4, corresponding to the lowest limit for the pH during cellular uptake. The tips of the prisms became rounded within minutes due to their high surface energy. Afterward, the dissolution process slowed down due to the presence of both PVP stabilizing Ag{100} sites and citrate blocking Ag{111} sites. On the contrary, nanospheres, solely stabilized by PVP, dissolved within 24 h. These results correlate with the finding that particles in both cell types have lost >90% of their volume within 24 h. hMSC's took up significantly more Ag from nanoprisms than from nanospheres, whereas HaCaT cells showed no preference for one particle shape. This can be rationalized by the large cellular interaction area of the plateletlike nanoprisms and the bending stiffness of the cell membranes. hMSC's have a highly flexible cell membrane, resulting in an increased uptake of plateletlike particles. HaCaT cells have a membrane with a 3 orders of magnitude higher Young's modulus than for hMSC. Hence, the energy gain due to the larger interaction area of the nanoprisms is compensated for by the higher energy needed for cell membrane deformation compared to that for spheres, leading to no shape preference.

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“…Thus, cancerous cells typically have a lower stiffness (they are also defined as 'soft') when compared to the tumor tissue that they form and to normal cell lines, property which allows them to migrate and eventually metastasize [74,75]. The reported bending stiffness is 100 kPa for HaCaT cells [76], and varies from 0.76 kPa [77] to 3.9 kPa [78] for A375 cells depending on the experimental setup [79,80]. Considering those stiffness values, the stronger cytotoxicity that we observed on A375 compared to HaCaT could be explained by the high capacity According to ISO 10993-5, cell viability results can be interpreted as following: >80% no cytotoxicity, 80-60% weak cytotoxicity, 60-40% moderate cytotoxicity, and <40% strong cytotoxicity [60].…”

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“…Besides, the cellular compartment contained a lower AgNPs percentage (of the total Ag content) compared to the AgNPs percentage in the exposure concentration in the apical compartment. This suggests a preference towards cellular uptake/association of ionic silver over AgNPs or possible dissolution of the AgNPs cellularly following their uptake [44][45][46].…”

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“…[19] The shape of the nanomaterial also plays a role in dissolution, cellular uptake, and reactivity. [20,21] For example, nanocubes of silver have been shown to be less toxic to the roots of the plant Lolium multiflorum than nanowires or quasi-spherical nanosilver particles. [21] In an in vivo daphnid study Nassar et al (2016) found that gold nanorods were more toxic and caused more generation of ROS than did nanospheres.…”