Non-specific cellular uptake of surface-functionalized quantum dots

Abstract

We report a systematic empirical study of nanoparticle internalization into cells via non-specific pathways. The nanoparticles were comprised of commercial quantum dots (QDs) that were highly visible under a fluorescence confocal microscope. Surface-modified QDs with basic biologically significant moieties, e.g. carboxyl, amino, and streptavidin, were used, in combination with surface derivatization with polyethylene glycol (PEG) for a range of immortalized cell lines. Internalization rates were derived from image analysis and a detailed discussion about the effect of nanoparticle size, charge and surface groups is presented. We find that PEG derivatization dramatically suppresses the non-specific uptake while PEG-free carboxyl and amine functional groups promote QD internalization. These uptake variations displayed a remarkable consistency across different cell types. The reported results are important for experiments concerned with cellular uptake of surface-functionalized nanomaterials, both when non-specific internalization is undesirable and when it is intended for material to be internalized as efficiently as possible.

Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection

“…The observed variations in timing of uptake between the cell lines (Figure 2A and B) may also be influenced by cell-related specificity of internalization mechanisms for quantum dots. It should be noted that phases 1 and 2 of quantum dot distribution in the cells were found earlier in the studies reported by Hoshino et al, 16 Clift et al, 20 and Jiang et al, 19 Kelf et al, 14 Williams et al, 15 and Corsi et al, 17 which showed formation of vesicular structures spread in the cytoplasm corresponding to phase 2. Phase 3, ie, localization of vesicular structures in the perinuclear region, was described by Zhang et al 22 and Xiao et al, 23 and reviewed by Parak et al 33 Phase 4 resembles the data on formation of multivesicular body-like structures and their redistribution in cytoplasm presented by Yuan et al 18 and Jiang et al 19 However, there has been no presentation of an overall picture illustrating the time-dependent nature of natural uptake and distribution of nontargeted negatively charged quantum dots in living cells.…”

“…Internalization of quantum dots can occur via several possible primary steps, ie, adsorption of proteins from the culture medium onto the surface of the quantum dots, followed by their internalization via receptor-mediated pathways 14 or nonspecific binding and clustering of the nanoparticles near cationic sites on the plasma membrane, triggering receptors and inducing subsequent endocytosis 12 ( Figure 7). The uptake process begins with adherence of quantum dots to cell surface receptors present in the plasma membrane.…”

“…1,11,12 Analysis of results presented in the literature reveals a very wide range of values for quantum dot internalization parameters, in particular, uptake time and intracellular localization. [13][14][15][16][17][18][19][20][21][22][23][24] This could be due to time-dependent changes in accumulation and intracellular distribution of quantum dots taking place even in a single cell line. The interpretation of results is even more complicated in the case of in vivo studies where the quantum dots would be internalized by different types of cells.…”

Transport of Nanoparticles through the Placental Barrier

“…The active transport systems play a key role in the intracellular transport of macromolecules and NP. Extensive studies have shown that NP internalization mainly occurs via endocytotic pathways and depends on NP properties (e.g., size, charge, functionalization) as well as on the cellular origin and physiology (Kelf et al 2010;Pi et al 2010;Tan et al 2010). Some authors report presence of transtrophoblastic channels which are thought to be membrane-lined tubular systems that originate from membrane invaginations of the basal syncytiotrophoblastic surface and cross the cell towards its apical surface (Kertschanska et al 1997;Benirschke and Kaufman 2000).…”

Interaction of polymer-coated silicon nanocrystals with lipid bilayers and surfactant interfaces

“…However, very little scrutiny has been directed at pure PEG in this regard, pre-sumably because of the assumed lack of interaction implicit in improved 'stealth'. Questions nonetheless persist about the uptake of nanoparticles with a pure-PEG corona [47,48].…”