Effect of Lipid Corona on Phenylalanine-Functionalized Gold Nanoparticles to Develop Stable and Corona-Free Systems

Abstract

Conventional gold nanoparticles (Au NPs) have many limitations, such as aggregation and subsequent precipitation in the medium of high ionic strength and protein molecules. Furthermore, when exposed to biological fluids, nanoparticles form a protein corona, which controls different biological processes such as the circulation lifetime, drug release profile, biodistribution, and in vivo cellular distribution. These limitations reduce the functionality of Au NPs in targeted delivery, bioimaging, gene delivery, drug delivery, and other biomedical applications. To circumvent these problems, there are numerous attempts to design corona-free and stable nanoparticles. Here, we report for the first time that lipid corona (coating of lipid) formation on phenylalanine-functionalized Au NPs (AuPhe NPs) imparts excellent stability against the high ionic strength of bivalent metal ions, amino acids, and proteins of different charges as compared to bare nanoparticles. Moreover, this work is focused on the ability of lipid corona formation on AuPhe NPs to prevent protein adsorption in the presence of cell culture medium (CCM), oppositely charged protein (e.g., histone 3), and human serum albumin (HSA). The results demonstrate that the lipid corona successfully protects the AuPhe NPs from protein adsorption, leading to the development of corona-free character. This unique achievement has profound implications for enhancing the biomedical utility and safety of these nanoparticles.

Stealth and Biocompatible Gold Nanoparticles through Surface Coating with a Zwitterionic Derivative of Glutathione

“…However, the ability of PEG to prevent protein adsorption hinges on several critical factors, including the length, architecture, and grafting density of the PEG chains covering the AuNP surface. , In addition, PEG minimizes protein adsorption but does not completely avoid it, and repeated PEG exposure in vivo induces the production of PEG-specific antibodies. , PEGylation can also substantially increase the overall hydrodynamic diameter (HD) of AuNPs. To overcome the limitations associated with PEG conjugation, various other protective coatings can be utilized, including peptides, proteins, lipids, polymers, and zwitterionic molecules, each with its own set of distinct advantages and disadvantages. ,− Zwitterionic molecules, in particular, have been increasingly pursued as superior nonfouling coatings for inorganic NPs. − Zwitterionic coatings are surrounded by a tightly bound, electrostatically induced hydration layer. This layer creates a large energy barrier and a strong repulsive force against nonspecific protein adsorption. − However, many zwitterionic ligands developed to date entail complicated synthesis and characterization procedures, which can pose challenges for laboratories lacking expertise in organic synthesis. ,− The lack of facile protocols to prepare zwitterionic-coated NPs may ultimately hinder further development and testing of these nanomaterials, thereby delaying their real-world clinical applications.…”

“…To overcome the limitations associated with PEG conjugation, various other protective coatings can be utilized, including peptides, proteins, lipids, polymers, and zwitterionic molecules, each with its own set of distinct advantages and disadvantages. 15 , 21 − 27 Zwitterionic molecules, in particular, have been increasingly pursued as superior nonfouling coatings for inorganic NPs. 28 − 30 Zwitterionic coatings are surrounded by a tightly bound, electrostatically induced hydration layer.…”