Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells

Abstract

We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).The chemical design and synthesis of nanoparticles have fueled the growth of nanotechnology. The foundation of nanotechnology research is based on the size and shape of the structures, where distinct optical, electronic, or magnetic properties can be tuned during chemical synthesis. There is an enormous interest in exploiting nanoparticles in various biomedical applications since their size scale is similar to that of biological molecules (e.g., proteins, DNA) and structures (e.g., viruses and bacteria). Furthermore, useful properties can be incorporated into the design of the nanoparticles for manipulation or detection of biological structures and systems. Nanoparticles are currently used in imaging, 1-6 biosensing, 7-9 and gene and drug delivery. 10-12As the field continues to develop, quantitative and qualitative studies on the cellular uptake of nanoparticles, with respect to their size and shape, are required in order to advance nanotechnology for biomedical applications. This will be important for assessing nanoparticle toxicity (i.e., if nanoparticles do not enter cells, they are less prone to killing cells or altering cellular function), for advancing nanoparticles for imaging, drug delivery, and therapeutic applications (i.e., how to maximally accumulate nanoparticles in cells, tumors, and organs?), and for designing multifunctional nanoparticles (i.e., are there dimensional limits to designing nanoparticles that can target and kill diseased cells?). Detailed studies of uptake kinetics of nanoparticles by cells have not been well characterized and quantified as a function of their size and shape (i.e., trends have not been determined). Most studies have focused on liposomes [13][14][15][16] and polymer particles, 17,18 which are generally larger than 100 nm. Furthermore, metallic, semiconductor, and carbon-based nanoparticles can be synthesized with greater size and shape variabilities than liposome and polymer particles.We selected gold nanoparticles as the model system for our studies; the rationale being that gold nanoparticles could be synthesized at a large size (1-100 nm diameter) and shape range (1:1 to 1:5 aspect ratio). Gold nanoparticles are also easy to characterize by the techniques of UV-vis spectrophotometry, inductively coupled plasma atomic emission spectroscopy (ICP-AES), and transmission electron microscopy (TEM). Furthermore, gold nanoparticles have recently been demonstrated...

Microglial Response to Gold Nanoparticles

“…36,37 Chan's group has shown that spheres, in particular 50 nm sized GNPs, are taken up to a significantly greater extent than rods, independently of their aspect ratio. 28,29 This observation has been confirmed by other studies. 38 So far, only two shapes (spheres vs rods) have been compared in terms of internalization.…”

“…In our studies, CTAB-coated gold spheres (10 11 GNPs/mL) lead to marked neural cell loss 24 h after exposure, while CTAB-coated gold rods exhibited a more modest reduction in viability, likely due to the increased uptake of spheres supporting the findings by Chan's group. 29 Dark-Field Microscopy and Hyperspectral Analysis of Gold Nanoparticles in Microglial Cells. Next, we performed intracellular imaging of GNPs using high contrast dark-field imaging ( Figure 3 and Supporting Information Figure S1).…”

Transfer of gold nanoparticles from the water column to the estuarine food web

“…Gold nanoparticles, including nanorods in this size range, have applications in industrial catalysis, chemical sensing and pharmaceutical technologies, and it is known they can be taken up by cells in culture [19][20][21][22][23] . This work reports the fate of gold nanoparticles in a complex ecosystem containing sediments, biofilms, primary producers, filter feeders, grazers and omnivores.…”

Nonendosomal cellular uptake of ligand‐free, positively charged gold nanoparticles

“…Previous studies have reported the internalization of chemically derived gold nanoparticles into several cell lines within 48 h or less, presuming or proving an endosomatic localization for the incorporated particles (8)(9)(10)(11). The latter raises the problem of transporting the particles into the cytosol to gain access to the location of interest.…”