(512a) Modulation of the Protein Corona, Deposition Efficiency, and the Nano-Bio Interface Under Physiologically Relevant Conditions

Colloidal gold nanoparticles (AuNPs) are being increasingly utilized in biomedical applications, such as drug/gene delivery and bio-imaging techniques.  However, the effectiveness of these procedures are highly dependent upon sustained, strong interactions between AuNPs and the surrounding environment; referred to as the nano-bio interface.  Recently, it has been established that this interface is reliant on the formation of a protein-NP complex.  The protein corona surrounding NPs is dynamic by nature and is dependent upon numerous factors including the environmental composition and specific physicochemical properties of the particles.  Previous studies have demonstrated that the corona structure mediates NP deposition efficiency, membrane exchanges, and mechanism of endocytosis; making it a critical factor in the use of AuNPs for drug and gene delivery applications.  However, little is currently known about how physiological variables, such as fluid flow and biological fluids outside of blood, modulate the protein-NP complex and subsequent particokinetics. 

Firstly, we demonstrated that the addition of shear stress, introduced through dynamic fluid movement within the cellular system, severely disrupted the protein corona surrounding 13 nm AuNPs.  Furthermore, within a dynamic environment, both the NP behavior and the nano-bio interface were modulated; culminating in a dramatic drop in AuNP deposition efficiency versus a static system.  As drug/gene delivery require high AuNP delivery to a target, this loss of NP transport potential highlights a current limitation within the field.  Moreover, circulating NPs have a strong likelihood of encountering multiple physiological environments, such as interstitial and lysosomal fluids; of which the influence on the nano-bio interface has yet to be explored.  We determined that when dispersed in these biological fluids, both the protein corona and the deposited AuNP dose was altered; as a function of original surface chemistry.  These alterations to the nano-bio interface can be directly correlated to NP behavior in accurate physiological fluids.  Furthermore, we identified a unique synergistic response to the cellular system during exposure to tannic acid coated AuNPs in conjunction with interstitial fluid: the induction of cytotoxicity. 

Given these results, it was clear that under the influence of physiologically relevant variables both the protein corona and the nano-bio interface were disrupted; resulting in a loss of AuNP deposition efficiency.  As effective use of AuNPs for drug/gene delivery requires specific cellular targeting, to a high degree, we next sought to utilize the protein corona as a means of improving AuNP-cellular interactions.  This was accomplished by generating a corona comprised solely of epidermal growth factor (EGF) around AuNPs prior to cellular introduction.  These EGF-AuNPs demonstrated an increase in cellular deposition over stock AuNPs, presumably through augmented binding to predominant EGF receptors on the cellular surface.  This study demonstrated that AuNP pretreatment with target proteins could improve cellular deposition, providing a potential means for improving nano-based delivery mechanisms.