Ultrasmall metallic nanoparticles and nanoclusters (usNPs) are a special type of nanostructure exhibiting distinctive physicochemical properties and in vivo behaviors, including improved renal clearance and tumor distribution. At present, however, the ability to precisely control the biobehaviors of usNPs is limited, partly because our understanding of their interactions in biological environments is incomplete. Therefore, we have been developing and applying a combination of biochemical and biophysical methodologies to gain fundamental knowledge on usNP-protein interactions, including their binding affinities, binding kinetics, and effects on protein structure and function. 

Engineered nanoparticles (NPs) have garnered significant attention in nanomedicine due to their ability to encapsulate and deliver poorly soluble drugs to targeted cells and tissues. However, despite decades of extensive research, the development of NP carriers that can selectively interact with and be efficiently internalized by specific cells remains a formidable challenge. One crucial yet often overlooked factor influencing the cellular binding and internalization of NPs is the cell-surface glycocalyx, a highly negatively charged carbohydrate-rich coat that surrounds the plasma membrane of all cells. To address this limitation, our current research investigates how the cell-surface glycocalyx might modulate the uptake of NPs. By understanding how NPs and the glycocalyx interact, we hope to improve our ability to control and optimize NP uptake in targeted drug delivery.