Mucin-Inspired, High Molecular Weight Virus Binding Inhibitors Show Biphasic Binding Behavior to Influenza A Viruses

Multivalent binding inhibitors are a promising new class of antivirals that prevent virus infections by inhibiting virus binding to cell membranes. The design of these inhibitors is challenging as many properties, for example, inhibitor size and functionalization with virus attachment factors, strongly influence the inhibition efficiency. Here, virus binding inhibitors are synthesized, the size and functionalization of which are inspired by mucins, which are naturally occurring glycosylated proteins with high molecular weight (MDa range) and interact efficiently with various viruses. Hyperbranched polyglycerols (hPGs) with molecular weights ranging between 10 and 2600 kDa are synthesized, thereby hitting the size of mucins and allowing for determining the impact of inhibitor size on the inhibition efficiency. The hPGs are functionalized with sialic acids and sulfates, as suggested from the structure of mucins, and their inhibition efficiency is determined by probing the inhibition of influenza A virus (IAV) binding to membranes using various methods. The largest, mucin-sized inhibitor shows potent inhibition at pm concentrations, while the inhibition efficiency decreases with decreasing the molecular weight. Interestingly, the concentration-dependent IAV inhibition shows a biphasic behavior, which is attributed to differences in the binding affinity of the inhibitors to the two IAV envelope proteins, neuraminidase, and hemagglutinin

Blood circulation of soft nanomaterials is governed by dynamic remodeling of protein opsonins at nano-biointerface

The blood circulation time is important to the biomedical application of nanomaterials. Here, the authors explore the effect of protein corona formation on the blood residency of nanomaterials and show circulation times are governed by the dynamic remodelling of protein opsonins in vivo

Carbon Nanoparticles as Visible-Light Photocatalysts for Efficient CO2 Conversion and Beyond

Increasing atmospheric CO2 levels have generated much concern, driving the ongoing carbon sequestration effort. A compelling CO2 sequestration option is its photocatalytic conversion to hydrocarbons, for which the use of solar irradiation represents an ultimate solution. Here we report a new strategy of using surface-functionalized small carbon nanoparticles to harvest visible photons for subsequent charge separation on the particle surface in order to drive the efficient photocatalytic process. The aqueous solubility of the catalysts enables photoreduction under more desirable homogeneous reaction conditions. Beyond CO2 conversion, the nanoscale carbon-based photocatalysts are also useful for the photogeneration of H2 from water under similar conditions

Effect of Injection Routes on the Biodistribution, Clearance, and Tumor Uptake of Carbon Dots

National Basic Research Program of China (973 Program) [2013CB733802]; National Science Foundation of China (NSFC) [81201086, 81201129, 81101101, 51273165]; Intramural Research Program of the NIBIB, NIH; Henry M. Jackson Foundation; NIH [K99/R00]The emergence of photoluminescent carbon-based nanomaterials has shown exciting potential in the development of benign nanoprobes. However, the in vivo kinetic behaviors of these particles that are necessary for clinical translation are poorly understood to date. In this study, fluorescent carbon dots (C-dots) were synthesized and the effect of three injection routes on their fate in vivo was explored by using both near-infrared fluorescence and positron emission tomography imaging techniques. We found that C-dots are efficiently and rapidly excreted from the body after all three injection routes. The clearance rate of C-dots is ranked as intravenous > intramuscular > subcutaneous. The particles had relatively low retention in the reticuloendothelial system and showed high tumor-to-background contrast. Furthermore, different injection routes also resulted in different blood clearance patterns and tumor uptakes of C-dots. These results satisfy the need for clinical translation and should promote efforts to further investigate the possibility of using carbon-based nanoprobes in a clinical setting. More broadly, we provide a testing blueprint for in vivo behavior of nanoplatforms under various injection routes, an important step forward toward safety and efficacy analysis of nanoparticles

Effect of Injection Routes on the Biodistribution, Clearance, and Tumor Uptake of Carbon Dots

The emergence of photoluminescent carbon-based nanomaterials has shown exciting potential in the development of benign nanoprobes. However, the <i>in vivo</i> kinetic behaviors of these particles that are necessary for clinical translation are poorly understood to date. In this study, fluorescent carbon dots (C-dots) were synthesized and the effect of three injection routes on their fate <i>in vivo</i> was explored by using both near-infrared fluorescence and positron emission tomography imaging techniques. We found that C-dots are efficiently and rapidly excreted from the body after all three injection routes. The clearance rate of C-dots is ranked as intravenous > intramuscular > subcutaneous. The particles had relatively low retention in the reticuloendothelial system and showed high tumor-to-background contrast. Furthermore, different injection routes also resulted in different blood clearance patterns and tumor uptakes of C-dots. These results satisfy the need for clinical translation and should promote efforts to further investigate the possibility of using carbon-based nanoprobes in a clinical setting. More broadly, we provide a testing blueprint for <i>in vivo</i> behavior of nanoplatforms under various injection routes, an important step forward toward safety and efficacy analysis of nanoparticles