Blood loss is the major cause of death in both civilian and battlefield traumas. Methods to staunch bleeding include pressure dressings and absorbent materials. For example, Quik-clot effectively halts bleeding by absorbing large quantities of fluid and concentrating platelets to augment clotting, but these treatments are limited to compressible and exposed wounds. An ideal treatment would halt bleeding only at the injury site, be stable at room temperature, be administered easily, and work effectively for internal injuries. We have developed synthetic platelets, based on ArgGly-Asp functionalized nanoparticles, that halve bleeding time after intravenous administration in a rat model of major trauma. The effects of these synthetic platelets surpass other treatments including recombinant factor VIIa, which is used clinically for uncontrolled bleeding. Synthetic platelets were cleared within 24 hours at a dose of 20 mg/ml, and no complications were seen out to 7 days after infusion, the longest time point studied. These synthetic platelets may be useful for early intervention in trauma and demonstrate the role that nanotechnology can have in addressing unmet medical needs.
Nanocomposite materials consisting of colloidal metal nanoparticles embedded in synthetic polymer hydrogels have attracted attention due to potential applications in catalysis, photonics, electronics, optics, and biomedicine.[1] Here we describe a method for synthesizing nanocomposite materials consisting of colloidal gold (Au) nanoparticles embedded in thermoresponsive poly(N-isopropylacrylamide) (PNIPAm) hydrogels. By incorporating thiol groups that have affinity to both Au 3+ ions and colloidal Au into the PNIPAm hydrogels, we demonstrate specific control over the size, morphology, and long-term stability of the Au nanoparticles by adjusting the concentration of thiols in the hydrogel side chains. Compared with the non-Au-containing PNIPAm hydrogels, the Au±PNIPAm nanocomposite hydrogels display remarkably different bulk properties of equilibrium swelling and thermoresponsive phase transition, which are related to the size and morphology, and possibly the surface charge, of the Au nanoparticles. One approach to synthesizing inorganic nanoparticles with potentially well-defined size and morphology is by using polymeric templates such as porous silica, [2a,b] block copolymers, [2c] dendrimers, [2d] lyotropic liquid crystals, [2e] and nonaqueous polymer resins [2f,g] and gels.
Undecanethiol (C11H23SH) and tri(ethylene glycol)-terminated undecanethiol (HO(C2H4O)3C11H22SH) self-assembled monolayers (SAMs) on clean gold surfaces were prepared and characterized. The SAMs were then immersed into either phosphate-buffered saline or calf serum. The SAM samples were investigated using several analytical techniques at numerous points over the next 35 days. Contact angles and current densities in voltammetry changed dramatically for the PBS samples over the time period, particularly after 21 days. Results indicate substantial loss of the integrity of the SAM. Similar alterations with time were observed for the calf serum samples in both contact angle and voltammetry measurements. X-ray photoelectron spectroscopy indicates that the likely origin is desorption of the alkanethiol moiety as evidenced by appreciable loss of the S 2p signal after 35 days.
The coiled‐coil‐based assembly of gold nanoparticles (see Figure and cover) is demonstrated. Control over the assembly and disassembly of nanostructures is achieved under mild conditions (near‐neutral pH and ambient temperature). The flexibility in design afforded by varying the peptide sequence to produce coiled coils with different stabilities is also highlighted by the generation of more stable binary nanoparticle systems with controlled spacing and architecture.
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