Multi-Domain Short Peptide Molecules for in Situ Synthesis and Biofunctionalization of Gold Nanoparticles for Integrin-Targeted Cell Uptake

Abstract

We describe design and synthesis model of multidomain (modular) peptides (MDPs), which direct a reaction cascade coupling the synthesis and surface functionalization of gold nanoparticles (AuNPs) in a single step. The synthesis is achieved via simple mixing of the aqueous solutions of auric acid and MDPs at room temperature without the addition of any surfactants or toxic intermediate reagents. This method allows facile control over the nanoparticle size between ∼2−15 nm, which opens a practical window for biomedical applications. In contrast to the conventional citrate-mediated methods, peptide-mediated synthesis and stabilization provide increased colloidal stability to AuNPs. As a proof of this concept, we demonstrate active targeting of human breast adenocarcinoma cell line (MCF7) using the one-step-prepared engineered AuNPs. Overall, we propose a single-step, chemically greener, biologically safer method for the synthesis and surface functionalization of gold nanoparticles in a sizecontrolled manner. The chemical versatility of the MDP design broadens the applicability of this strategy, thereby emerging as a successful alternative for the currently available nanoparticle preparation technologies.

Intracellular Accumulation of Gold Nanoparticles Leads to Inhibition of Macropinocytosis to Reduce the Endoplasmic Reticulum Stress

“…To understand endocytosis and exocytosis behavior, we first investigated the mechanism of AuNPs uptake by HUVECs. Although the uptake mechanisms of bare and surface-functionalized AuNPs in a variety of sizes and shapes have been characterized in the literature, their internalization is difficult to generalize and may depend on processes such as macropinocytosis 37 , phagocytosis 38 39 , receptor mediated endocytosis 7 (clathrin- or caveolae-mediated endocytosis) and transcytosis 40 . Therefore, three of these major pathways (macropinocytosis, caveolae-mediated endocytosis, and clathrin-mediated endocytosis) were blocked by inhibitor treatment to observe whether AuNP uptake depended on any of these mechanisms ( Table S1 ).…”

“…This result suggests that AuNPs were predominantly entering into HUVECs via macropinocytosis. Gulsuner et al, showed that MDP-AuNPs which contains RGD sequence as targeting moiety enters into breast cancer cells via both clathrin-mediated endocytosis and macropinocytosis pathway 37 . The cells might use non-specific entry routes for endocytosis of non-functionalized AuNPs.…”

Decoration of gold nanoparticles with cysteine in solution: reactive molecular dynamics simulations

“…17,18 These molecules, besides being stably adsorbed on the AuNP surfaces, self-assemble and create dense networks of interconnected structures which prevent water from reaching the metal supports. 19,20 Moreover, while the thiol groups form strong bonds with the gold interface and stabilize the substrate, the other portions of the chains are involved in interactions with the surrounding environment (solvent, peptides, proteins, enzymes, lipids, etc.). 21,22 Given these premises, it would be crucial to disclose at the atomic level the behavior of AuNPs in solution when thiolcontaining amino acids (for example cysteine) are adsorbed on their faces and to understand in detail the dynamics of surface functionalization.…”

Green Peptide–nanomaterials; A Friendly Healing Touch for Skin Wound Regeneration

“…The peptides are natural compounds in synthesizing the biocompatible metal nanoparticles in mild conditions [135][136][137][138][139]. They act as reducing agent as well as the capping agent during nanomaterials synthesis.…”

“…In another research, Giese et al explained the synthesis of AgNPs under electron transfer conditions [136] where Ag+ ions bound by a histidine as the Ag-binding amino acid and a tyrosine as a photo inducible electron donor of the bound peptide. The application of a multidomain peptide (DOPA) for single-step, size-controlled synthesis of biofunctionalized AuNPs was described by Tekinay and coworkers [137]. The size-controlled synthesis of AuNPs was possible due to the presence of 3,4-dihydroxy-L-phenylalanine (L-DOPA) functional group in the peptide which is reductive in nature.…”