Integration of Peptides for Enhanced Uptake of PEGylayed Gold Nanoparticles

Abstract

Polyethylene glycol (PEG) has promoted the prospective applications of nanoparticles (NPs) in cancer therapy. PEG is used to evade the immune system allowing NPs accumulation within the tumor using its leaky vasculature. However, the cellular uptake of PEG-coated (PEGylated) NPs is lower in comparison to non-PEGylated NPs since PEG minimizes surface binding of ligands that mediate NP endocytosis. For improved outcome in therapeutic applications, it is necessary to enhance the uptake of PEGylated NPs. We added a peptide containing an integrin binding domain known as the RGD sequence to the NP surface in addition to PEG. We used gold NPs (GNPs) of sizes 14, 50, and 70 nm in this study. Our in vitro data for HeLa cells show enhanced uptake for NPs coated with both PEG and the peptide in comparison to PEGylated GNPs. NPs of size 50 nm had the highest uptake among the three sizes for all GNP surfaces. A similar size-dependent trend was observed for MDA-MB-231 cells for as-made GNPs with lower uptake in comparison to HeLa cells. However, only 14 nm peptide-modified PEGylated NPs had enhanced uptake. Hence, NP uptake was found dependent on cell type and NP surface properties. A properly designed NP system with both PEG and cell membrane targeting peptides can be used to protect it from the immune system and promote internalization by cells upon entry into tumor environment.

Gold Nanoparticle Uptake in Tumor Cells: Quantification and Size Distribution by sp-ICPMS

“…Overall, the uptake of gold nanoparticles into MDAMB231 cells was twice as high as into T47D cells, whatever the time of exposure, illustrating how important the quantification of nanoparticle uptake within the cells is for understanding AuNP biological effects. Such differences between cell lines have been reported in several publications but have not been rationalized yet [37][38][39]. For comparison, in MDAMB231 cells incubated with 14 or 50 nm AuNPs functionalized by thiolated PEG of MW 2000, Cruje and Chithrani found 160 or 40 particles per cell, respectively, which is consistent with our results [37].…”

“…Such differences between cell lines have been reported in several publications but have not been rationalized yet [37][38][39]. For comparison, in MDAMB231 cells incubated with 14 or 50 nm AuNPs functionalized by thiolated PEG of MW 2000, Cruje and Chithrani found 160 or 40 particles per cell, respectively, which is consistent with our results [37].…”

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells

“…The benefits of PEG on prolonging circulation time of colloidal carriers are well known (Cruje and Chithrani, 2015), but in this study, however, it is the role of PEG as a component part of the particulate matrix on cellular uptake that is of particular importance.…”

The Effect of Nanoparticle Size on In Vivo Pharmacokinetics and Cellular Interaction

“…Although the exact optimal diameter varies between applications, a ligand-coated, spherical nanoparticle between 30 and 60 nm in diameter can recruit and bind to enough cellular receptors to drive the membrane-wrapping process without a receptor shortage affecting endocytosis [31,32]. Most in vitro studies show a maximum cellular uptake within the 10-60 nm range, regardless of core composition or surface charge [9,12,22,[33][34].…”