Platelet-Inspired Intravenous Nanomedicine for Injury-Targeted Direct Delivery of Thrombin to Augment Hemostasis in Coagulopathies.

Severe hemorrhage associated with trauma, surgery, and congenital or drug-induced coagulopathies can be life-threatening and requires rapid hemostatic management via topical, intracavitary, or intravenous routes. For injuries that are not easily accessible externally, intravenous hemostatic approaches are needed. The clinical gold standard for this is transfusion of blood products, but due to donor dependence, specialized storage requirements, high risk of contamination, and short shelf life, blood product use faces significant challenges. Consequently, recent research efforts are being focused on designing biosynthetic intravenous hemostats, using intravenous nanoparticles and polymer systems. Here we report on the design and evaluation of thrombin-loaded injury-site-targeted lipid nanoparticles (t-TLNPs) that can specifically localize at an injury site via platelet-mimetic anchorage to the von Willebrand factor (vWF) and collagen and directly release thrombin via diffusion and phospholipase-triggered particle destabilization, which can locally augment fibrin generation from fibrinogen for hemostatic action. We evaluated t-TLNPs in vitro in human blood and plasma, where hemostatic defects were created by platelet depletion and anticoagulation. Spectrophotometric studies of fibrin generation, rotational thromboelastometry (ROTEM)-based studies of clot viscoelasticity, and BioFlux-based real-time imaging of fibrin generation under simulated vascular flow conditions confirmed that t-TLNPs can restore fibrin in hemostatic dysfunction settings. Finally, the in vivo feasibility of t-TLNPs was tested by prophylactic administration in a tail-clip model and emergency administration in a liver-laceration model in mice with induced hemostatic defects. Treatment with t-TLNPs was able to significantly reduce bleeding in both models. Our studies demonstrate an intravenous nanomedicine approach for injury-site-targeted direct delivery of thrombin to augment hemostasis.

Spectroscopic response of soil organic matter in mining area to Pb/Cd heavy metal interaction: A mirror of coherent structural variation.

Understanding the interaction between heavy metals and soil organic matter (SOM) in mining area is important for the clarification of the environmental behaviors of heavy metals. In this work, the coherence of structural changes of SOM during interaction with Pb2+ and Cd2+ ions were examined by using UV-vis/fluorescence spectroscopy coupled with correlation analyses. The result showed that phenolic- and carboxylic-like groups of SOM were engaged in the complexation of heavy metals (Pb2+ and Cd2+) with SOM, resulting in the formation of highly conjugated macromolecules/aggregates and an increase in molecular weight/size. Fluorescent humic-like, fulvic-like, and protein-like species were involved in the binding with Pb2+/Cd2+ ions, which were closely correlated with phenolic-like and carboxylic-like constitutes. SOM was more favorable to bind with Pb2+ ions than Cd2+ ions, with a less susceptive of SOM structure to Pb2+/Cd2+ ions in the mining area compared to those off the mining area under heavy metal stress. These results may provide a new insight for the treatment and remediation of heavy metal-polluted soil in mining area.

Structural substitution for SO4 group in tooeleite crystal by As(V) and As(III) oxoanions and the environmental implications.

Two different SO4-free tooeleite were prepared for the first time through structural substitution for SO4 group by As(V) and As(III). As(III)-tooeleite and As(V)-tooeleite have similar crystalline structure to SO4-tooeleite but incorporate different anions in the interlayer space. The removal of As can reach 94% by forming SO4-free tooeleite crystals, and As leaching in TCLP tests can be much lower than that of SO4-tooeleite. Therefore, SO4-free tooeleite crystals are of great potential in As removal and immobilization. Moreover, our study indicates the different affinities of Fe(III) towards As(III), As(V) and SO4, which can explain that a) the coordination structure of As(III)-tooeleite is much closer to the ideal crystal structure but easily affected by As(V) and SO4 group; b) tooeleite mineral found in natural environments is commonly a SO4-containing mineral and associated with scorodite due to the abundance of As(V) and SO4 group.