Surface Chemistry of Quantum Dots Determines Their Behavior in Postischemic Tissue

The behavior of quantum dots (QDs) in the microvasculature and their impact on inflammatory reactions under pathophysiological conditions are still largely unknown. Therefore, we designed this study to investigate the fate and effects of surface-modified QDs in postischemic skeletal and heart muscle. Under these pathophysiological conditions, amine-modified QDs, but not carboxyl-QDs, were strongly associated with the vessel wall of postcapillary venules and amplified ischemia-reperfusion-elicited leukocyte transmigration. Importantly, strong association of amine-QDs with microvessel walls was also present in the postischemic myocardium. As shown by electron microscopy and verified by FACS analyses, amine-modified QDs, but not carboxyl-QDs, were associated with endogenous microparticles. At microvessel walls, these aggregates were attached to endothelial cells. Taken together, we found that both the surface chemistry of QDs and the underlying tissue conditions (<i>i.e.</i>, ischemia-reperfusion) strongly determine their uptake by endothelial cells in microvessels, their association to endogenous microparticles, as well as their potential to modify inflammatory processes. Thus, this study strongly corroborates the view that the surface chemistry of nanomaterials and the physiological state of the tissue are crucial for the behavior of nanomaterials <i>in vivo.</i

Surface Chemistry of Quantum Dots Determines Their Behavior in Postischemic Tissue

The behavior of quantum dots (QDs) in the microvasculature and their impact on inflammatory reactions under pathophysiological conditions are still largely unknown. Therefore, we designed this study to investigate the fate and effects of surface-modified QDs in postischemic skeletal and heart muscle. Under these pathophysiological conditions, amine-modified QDs, but not carboxyl-QDs, were strongly associated with the vessel wall of postcapillary venules and amplified ischemia-reperfusion-elicited leukocyte transmigration. Importantly, strong association of amine-QDs with microvessel walls was also present in the postischemic myocardium. As shown by electron microscopy and verified by FACS analyses, amine-modified QDs, but not carboxyl-QDs, were associated with endogenous microparticles. At microvessel walls, these aggregates were attached to endothelial cells. Taken together, we found that both the surface chemistry of QDs and the underlying tissue conditions (<i>i.e.</i>, ischemia-reperfusion) strongly determine their uptake by endothelial cells in microvessels, their association to endogenous microparticles, as well as their potential to modify inflammatory processes. Thus, this study strongly corroborates the view that the surface chemistry of nanomaterials and the physiological state of the tissue are crucial for the behavior of nanomaterials <i>in vivo.</i

The Endothelial Glycocalyx Controls Interactions of Quantum Dots with the Endothelium and Their Translocation across the Blood–Tissue Border

Advances in the engineering of nanoparticles (NPs), which represent particles of less than 100 nm in one external dimension, led to an increasing utilization of nanomaterials for biomedical purposes. A prerequisite for their use in diagnostic and therapeutic applications, however, is the targeted delivery to the site of injury. Interactions between blood-borne NPs and the vascular endothelium represent a critical step for nanoparticle delivery into diseased tissue. Here, we show that the endothelial glycocalyx, which constitutes a glycoprotein–polysaccharide meshwork coating the luminal surface of vessels, effectively controls interactions of carboxyl-functionalized quantum dots with the microvascular endothelium. Glycosaminoglycans of the endothelial glycocalyx were found to physically cover endothelial adhesion and signaling molecules, thereby preventing endothelial attachment, uptake, and translocation of these nanoparticles through different layers of the vessel wall. Conversely, degradation of the endothelial glycocalyx promoted interactions of these nanoparticles with microvascular endothelial cells under the pathologic condition of ischemia–reperfusion, thus identifying the injured endothelial glycocalyx as an essential element of the blood–tissue border facilitating the targeted delivery of nanomaterials to diseased tissue