Abstract
The interaction between nanoparticles (NPs) and biological environments is profoundly influenced by a stable, strongly adsorbed "hard" protein corona. This corona significantly determines the NPs' pharmacokinetics and biological destiny. Our study delves into the mechanisms by which colloidal Au nanocrystals that are synthesized electrochemically without surface-capping organic ligands, known as CNM-Au8, traverse the blood-brain barrier (BBB) and target human brain tissue for treating neurodegenerative disorders. We discovered that upon interaction with human plasma, CNM-Au8 gold nanocrystals (AuNCs) effectively attract a variety of crucial apolipoproteins, notably apolipoproteins E, to their surfaces. This interaction likely facilitates their passage through the BBB. Furthermore, the coronas of these AuNCs exhibit a substantial presence of albumin and a notable absence of opsonin-based proteins, contributing to prolonged blood circulation. These characteristics align well with the clinical performance observed for the CNM-Au8 NCs. This study highlights that AuNCs with intentionally engineered structures and surfactant-free surfaces can create a distinct protein corona composition. This finding holds significant promise for the development of advanced therapeutic agents aimed at combating neurodegenerative diseases.
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