Targeted Nanoparticle Binding to Hydroxyapatite in a High Serum Environment for Early Detection of Heart Disease

Abstract

The impact of the protein-rich in vivo environment on targeted binding of functionalized nanoparticles has been an active field of research over the past several years. Current research aims at better understanding the nature of the protein corona and how it may be possible for targeted binding to occur even in the presence of serum. Much of the current research focuses on nanoparticles targeted to particular cell receptors or features with the aim of cellular uptake. However, similar research has not been performed on nanoparticles that are targeted to non-protein disease features, such as hydroxyapatite (HA). HA is a crystalline calcium-phosphate mineral that is present in large quantities in bone, and in smaller quantities in diseased cardiovascular tissue in cases of atherosclerosis or various stenoses. Our work aims to gain a better understanding of the behavior of PEGylated, peptide-coated superparamagnetic iron oxide nanoparticles (SPIONs) in a biologically-relevant high-protein environment (50% serum). We first determined that specific binding to HA occurs at significantly higher rates than non-specific binding in the absence of serum protein. We then examined nanoparticle interactions with serum proteins, including determination of the relative quantities of protein in the hard vs. soft protein corona. Finally, we examined specific and non-specific binding of targeted SPIONs in 50% serum, and determined that targeted binding may still occur with significant (p < 0.05) selectivity. We hypothesize that this may be because the nature of the binding interactions between the peptides and the HA are, by definition, less specific than the protein-protein interactions required for nanoparticles to bind to specific cells or cell features. These results suggest that these targeted SPIONs may be further developed for use in early detection of heart diseases such as atherosclerosis and aortic stenosis.

The Effect of Doping on the Electrical and Dielectric Properties of Hydroxyapatite for Medical Applications: From Powders to Thin Films

“…It is important to mention that the introduction of ion substitution and the doping of transition elements into the HA matrix have opened new avenues for the utilization of HA-based materials in the realm of medical and pharmaceutical sciences [34][35][36].…”

Understanding the Biomolecular Coronas of High-Density Lipoproteins on PEGylated Au Nanoparticles: Implication for Lipid Corona Formation in the Blood

“…In this regard, understanding protein coronas is critical in the field of nanomedicine. Over the past decade, extensive investigations have been performed for understanding protein coronas and their biological impacts. − The investigation has evolved to exploit the protein coronas for improving the efficacy of nanomedicines, for example, development of long-circulating NPs with improved targeting and drug delivery capability. − In contrast to protein coronas, coronas of other biogenic molecules such as lipids have been overlooked in these investigations, despite the apparent involvement of the latter in biomolecular coronas on NPs, which may additionally exert their own specific functions in bio-nano interactions in the biological systems. Therefore, the understanding of biomolecular coronas of biogenic molecules beyond proteins has emerged as an important research subject in recent years. − …”

An interview with Joyce Y Wong: ensuring all voices in biomaterials community are heard

“…aimbe.org/#inspire. Other projects with a clinical focus include: 'development of targeted nano-and micro-particle contrast agents for multi-modal (magnetic resonance, ultrasound, and optical) detection of calcific heart valves [11]; and engineering biomimetic systems to study restenosis and metastatic cancer [12]'.…”