Understanding the Cellular Uptake of pH-Responsive Zwitterionic Gold Nanoparticles: A Computer Simulation Study

Abstract

Surface functionalization of nanoparticles (NPs) with stealth polymers (e.g., hydrophilic and zwitterionic polymers) has become a common strategy to resist nonspecific protein adsorption recently. Understanding the role of surface decoration on NP-biomembrane interactions is of great significance to promote the application of NPs in biomedical fields. Herein, using coarse-grained molecular dynamics (CGMD) simulations, we investigate the interactions between stealth polymer-coated gold nanoparticles (AuNPs) and lipid membranes. The results show that AuNPs grafted with zwitterionic polymers can more easily approach the membrane surface than those coated with hydrophilic poly(ethylene glycol) (PEG), which can be explained by the weak dipole-dipole interaction between them. For zwitterionic AuNPs which can undergo pH-dependent charge conversion, different interaction modes which depend on the polymer protonation degree are found. When the protonation degree is low, the particles just adsorb on the membrane surface; at moderate protonation degrees, the particles can directly translocate across the lipid membrane through a transient hydrophilic pore formed on the membrane surface; the particles are fully wrapped by the curved lipid membrane at high protonation degrees, which may lead to endocytosis. Finally, the effect of polymer chain length on the cellular uptake of zwitterionic polymer-coated AuNPs is considered. The results demonstrate that longer polymer chain length will block the translocation of AuNPs across the lipid membrane when the protonation degree is not high; however, it can improve the transmembrane efficiency of AuNPs at high protonation degrees. We expect that these findings are of immediate interest to the design and synthesis of pH-responsive nanomaterials based on zwitterionic polymers and can prompt their further applications in the field of biomedicine.

Surface Regulation Towards Stimuli‐Responsive Luminescence of Ultrasmall Thiolated Gold Nanoparticles for Ratiometric Imaging

“…To elucidate the mechanism how the thiolate surface ligands regulate the effect of the amine molecules (e.g., EDA) on the stimuli‐responsive emission from the thiolated AuNPs, MD simulations were performed, whose feasibility has been widely proven in studying interactions between ligands coated metal NPs and various other molecules . The thiolated AuNPs coated with three different surface ligands were simulated in EDA solutions ( C EDA : 10.0 or 100.0 m m ), the number of EDA molecules adsorbed around the different surface‐ligand coated AuNPs was quite different, among which MPS‐AuNPs absorbed the highest number of EDA molecules ( Figure a; Figure S14, Supporting Information).…”

The long life of unicorns

“…This disappointing physical reality has not prevented the publication of a large number of theoretical articles studying the diffusion of nanoparticles through membranes as if that hypothetical phenomenon were relevant to drug delivery and nanoparticle toxicity. [7][8][9][10][11][12][13] We will argue that these articles, instead of helping the understanding of interactions between nanoparticles and cells, sustain the unicorn. For example, they add to the confusion over a simple scientific question, namely, "do nanoparticles enter cells by diffusing through lipid membranes?"…”

“…27 Third, authors may claim that there is experimental evidence for the diffusion of nanoparticles through membranes. However, a non-exhaustive analysis reveals two distinct patterns: (1) articles where the claim is presented as common knowledge 7,[10][11][12] , such as it is not backed up by any reference to experimental evidence; and (2) articles where the introduction gives the impression that such experimental evidence exists but, on closer inspection, that is not what the references provided show. 8,9,13,22,28,29 9,22,29 There are also several theoretical articles [30][31][32][33][34] devoted to modeling stripy nanoparticle diffusion through membranes, but both the existence of those structures and their special properties are disputed.…”

Advances in the Experimental and Theoretical Understandings of Antibiotic Conjugated Gold Nanoparticles for Antibacterial Applications

“…Although the interaction of AuNPs with the cell membrane (both bacterial and animal cell) is studied in detail, there is a lack of studies on the interaction of antibiotic conjugated AuNPs with bacterial cells and opens new directions for theoretical research . However, few studies show that the interaction of antibiotic molecules to the AuNPs is very crucial for investigate the increasing activity of the antibiotic molecules .…”