In‐situ Investigations on Gold Nanoparticles Stabilization Mechanisms in Biological Environments Containing HSA

Abstract

Nanoparticles (NPs) developments advance innovative biomedical applications. However, complex interactions and the low colloidal stability of NPs in biological media restrict their widespread utilization. The influence of NPs properties on the colloidal stability for gold NPs with 5 and 40 nm in diameter with two surface modifications, methoxy‐polyethylene glycol‐sulfhydryl (PEG) and citrate, in NaCl and human serum albumin (HSA) protein solution, is investigated. This study is based on small‐angle X‐ray scattering (SAXS) methods allowing the in‐situ monitoring of interactions in physiological conditions. The PEG coating provides high colloidal stability for NPs of both sizes. For 5 nm NPs in NaCl solution, a stable 3D self‐assembled body‐centered cubic (BCC) arrangement is detected with an interparticle distance of 20.7 ± 0.1 nm. In protein solution, this distance increases to 21.9 ± 0.1 nm by protein penetration inside the ordered structure. For citrate‐capped NPs, a different mechanism is observed. The protein particles attach to the NPs surfaces, and an appropriate concentration of proteins results in a stable suspension. Cryogenic transmission electron microscopy (Cryo‐TEM), UV–visible spectroscopy, and dynamic light scattering (DLS) support the SAXS results. The findings will pave the way to design and synthesize NPs with controlled behaviors in biomedical applications.

Time-Resolved Study on Self-Assembling Behavior of PEGylated Gold Nanoparticles in the Presence of Human Serum Albumin: A System for Nanomedical Applications

“…This is the starting point of NP ordering. Our earlier study shows that this peak corresponds to the (011) scattering plane in a BCC structure …”

“…Compared to the NPs-NaCl system, the (011) peak position locates a smaller q-range, indicating the proteins' presence inside the ordering domains and, consequently, domain expansion. 1 In addition, the peak intensity at the time points observed in the dynamic system is lower than the peak intensity at the corresponding times in the NPs-NaCl solution, and the second peak is not visible. These differences show that the ordering of NPs takes place much slower in this system.…”

“…Our earlier study shows that this peak corresponds to the (011) scattering plane in a BCC structure. 1 In addition, after 75 s, the second ordering peak appears as a shoulder ((112) scattering plane of the BCC structure). The intensity of the peaks increases and after 100 s, they are even more apparent.…”

“…It provides steric stabilization and a short-range repulsive hydration layer around the NPs, creating excellent long-term stability under high ionic strength (IS) and extreme pH conditions . In our previous study on gold NP colloidal stability in biological environments, a unique mechanism for 5 nm PEGylated gold NPs was discovered. In saline solution, upon increasing IS, these particles self-assemble in ordered domains with a body-centered cubic (BCC) arrangement, thereby maintaining their colloidal stability.…”

“…Nanoparticle (NP) colloidal stability in different environments is a crucial parameter that strongly affects NPs’ bio response and efficiency in biomedical applications. There are two main approaches to NP stabilization: (a) electrostatic stabilization by surface charge and (b) steric stabilization by polymer grafting on the NP surface. , Following the second approach, when two polymer-coated NPs approach, the polymer coatings’ outermost layers start to interact, and the NPs repel each other. PEG is the most used polymer for ensuring biocompatibility and stabilization of NPs in nanobiomedical applications.…”