Nanoparticle Geometry and Surface Orientation Influence Mode of Cellular Uptake

Abstract

The overall goal of this project is to determine the uptake patterns of silica nanoparticle geometries in model cells, in order to aid in the identification of the role of geometry on cellular uptake and transport. In our experiments we observed a significant difference in the viability of two phenotypes of primary macrophages; immortalized macrophages exhibited similar patterns. However, both primary and immortalized epithelial cells did not exhibit toxicity profiles. Interestingly uptake of these geometries in all cell lines, exhibited very different time dependent patterns. A screening of a series of chemical inhibitors of endocytosis was performed to isolate the uptake mechanisms of the different particles. The results show that all geometries exhibit very different uptake profiles and that this may be due to the orientation of the nanoparticles when they interact with the cell surface. Additionally, evidence suggests that these uptake patterns initialize different downstream cellular pathways, dependent on cell type and phenotype.

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

“…Far than chemical composition, size and shape are crucial factors determining the relationships between nanoparticles and increasingly complex biological systems (namely from cells to entire organisms) in critical aspects such as organ specificity and biodistribution [36][37][38][39][40], toxicity [41], and cell uptake and fate [39,[42][43][44][45]. Although previously checked in several types of nanostructures, mainly in crystalline nano-and micromaterials, the present study is the first evaluation of form (geometry) and function (cellular uptake) of protein nanoparticle populations.…”

Magnetic nanoparticles for precision oncology: theranostic magnetic iron oxide nanoparticles for image-guided and targeted cancer therapy

“…It has been shown that size of IONPs has a significant effect on their in vivo behavior and uptake by cells. Changes in nanoparticle size and shape could lead to alterations in receptor cross-linking and cellular responses [38][39][40]. It is generally agreed that nanoparticles at diameters ranging from 10 to 100 nm are optimal for in vivo applications with acceptable pharmacokinetics.…”

Macrophage uptake of cylindrical microparticles investigated with correlative microscopy

“…InteracƟons with biological systems differ for non-spherical parƟcles, opening up new opƟons for the design of drug delivery systems [1][2][3].…”

“…ModificaƟon of the geometry changes the Ɵme and mechanism required for uptake [3]. As a consequence, non-spherical parƟcles such as cylindrical parƟcles have the potenƟal to control clearance processes, a core prerequisite for a sustained release system for therapeuƟcs [2,4].…”