Cellular Uptake of Gold Nanoparticles and Their Movement in 3D Multicellular Tumor Spheroids: Effect of Molecular Weight and Grafting Density of Poly(2‐hydroxyl ethyl acrylate)

Abstract

It is known that the size of gold nanoparticles (GNPs) is not the only determining factor in the uptake by cells such as cancer cells. The surface functionalization plays a crucial role, in particular the nature of the ligand as well as the molecular weight and the grafting density. Here, poly(2-hydroxy ethyl) acrylate (pHEA) with molecular weights ranging from 10, 20 to 39 g mol −1 via reversible addition-fragmentation chain transfer polymerization is synthesized. These polymers are used directly to coat GNPs with sizes of 20, 40, and 70 nm as the trithiocarbonate functionality can strongly bind to the gold surface. The library of nine GNP is found to be nontoxic against lung carcinoma cells A549 and has negligible albumin protein absorption as determined by quartz crystal microbalance. Laser scanning confocal microscopy and flow cytometry reveal that GNP coated with medium length pHEA displays the highest cellular uptake while the effect of the size is not statistically significant. In contrast, multicellular tumor spheroids, which is a 3D model that simulates the tissue, enable the penetration of GNP coated with the longest pHEA chain while it also appears that smaller GNPs have now a clear advantage.The authors declare no conflict of interest.

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

“…An exploration of gold nanorods, nanospheres, and oligonucleotide-functionalized nanospheres was undertaken by Rane et al who showed the difference in uptake profiles present in a 3D model compared to the 2D monolayer [ 43 ]. Further studies on how functionalization and size of the GNPs have been explored recently, all agreeing that smaller GNPs will more effectively penetrate deeper into the cells [ 44 , 45 ]. More complex in vivo systems can also be reproduced in a spheroid model, such as a blood-brain barrier made up multiple cell types in a multicellular spheroid.…”

Benchtop X-ray fluorescence imaging as a tool to study gold nanoparticle penetration in 3D cancer spheroids

“…There is limited information in the literature about how ECM inuences nanoparticle penetration into tumours. [6][7][8][9] This is partially due to the fact that most studies rely on complex animal models, especially human tumour xenogras. These models are expensive, time-consuming, and have been raising more ethical concerns.…”

Adsorption of Polymer-Grafted Nanoparticles on Curved Surfaces

“…Therefore, consideration of the effect of various curvatures on the colloid-surface interaction forces can help expand this technique to include various degrees of roughness and concave surfaces as well. However, only limited studies have been conducted to date on the adhesion of PGNs as a function of surface curvature [17][18][19].…”