The Effects of Chemical Functionalization vs. Biological Functionalization on Nanoparticle Binding Affinity
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The Effects of Chemical Functionalization vs. Biological Functionalization on Nanoparticle Binding Affinity Jason J Benkoski, Julia J Patrone, James Crookston, Huong Le, and Jennifer Sample Milton Eisenhower Research Center, The Johns Hopkins University Applied Physics Laboratory, 11100 Johns Hopkins Rd, Laurel, MD, 20723 ABSTRACT Due to their small size, high diffusivity, and chemically active surfaces, nanoparticles share much in common with water-soluble proteins. These similarities have generated great interest in using biofunctional nanoparticles as a route to deliver targeted therapeutics. Already nanoparticles have found applications in the hyperthermia of tumors, personal care lotions, and tissue scaffolding. Our study focuses on the targeting of such nanoparticles to specific biological sites. It therefore seeks to identify the factors that control the migration and capture of nanoparticles within living systems. In particular, we examine the affinity of anti-collagen coated magnetite nanoparticles for collagen IV-coated surfaces under flow stress. The studies are performed within microfluidic devices that are designed to mimic various fluid flow patterns within the body. We find, in this case, a large background signal due to nonspecific binding. Further examination shows a correlation between chemical functionality (e.g., surface charge, hydrophilicity) that suggests that a balanced approach between biological functionality and chemical functionality may reduce the background from nonspecific binding to acceptable levels. INTRODUCTION A promising alternative to traditional pharmaceuticals is an injectable nanoparticle carrier. Relative to simple organic molecules, nanoparticles potentially offer improved sitespecific delivery, increased intracellular penetration, and protection of the drug against degradation.1 These attributes arise from the small size, high diffusivity, and large specific surface area. Nanoparticles, in this sense, mimic the molecular machinery of the body. Site-specific delivery, in particular, has generated considerable interest. One of the most common methods is to coat the nanoparticles with an antibody that is specific for a surface at or near the region of interest. To investigate the efficacy of this method, we have chosen collagenIV antibodies and collagen-IV coated surfaces as our model system. This particular system was chosen because collagen-IV is a major component of the elastica interna in arterial walls and since most injectable nanoparticle carriers are introduced through the vascular system. From an application standpoint, this system may potentially lead to nanoparticle treatments for arteriovascular trauma, such as aneurysms. The clinical importance of aneurysms is witnessed by the fact that 27,000 Americans are estimated to suffer from ruptured intracranial aneurysms each year.2 The disorder is treatable because aneurysms take time to develop and grow before catastrophic failure.3 Unfortunately, current treatments involve invasive surgery, with either t
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