After an initial mechanical injury, such as in spinal cord injury, inevitable necrosis and the inflammatory response cause a cascade of biochemical secondary injury in the surrounding areas, sometimes greater than the primary traumatic injury itself. We describe a nanomedicine approach to reduce this secondary injury.A destructive, regenerating culprit, acrolein (2-propenal), has been implicated in this secondary injury cascade. The aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation, effectively regenerating itself. When acrolein attacks essential proteins and lipids, it creates a feed forward loop of oxidative stress in both the primary injury area and the surrounding areas, damaging tissue that is stressed but still functional. A small molecule used for hypertension, hydralazine, has been found to 'scavenge' acrolein after injury, but its delivery and short half-life hinder its application in halting the oxidative cascade.Nanomedical systems broaden the range of therapeutic availability and efficacy over conventional medicine. They allow for targeted delivery of therapeutic molecules to tissues of interest, reducing side effects of wayward therapies in unwanted areas. Nanoparticles made from silica form porous networks that can carry therapeutic molecules throughout the body. Most silica chemistry requires relatively mild conditions, and their diameter, shape, pore size, and interactive properties can be changed based on the reaction conditions. To attenuate the acrolein cascade and improve therapeutic availability, we have used a one-step, modified St�ber method to synthesize two types of silica nanoparticles. Both particles are stealth-coated with poly(ethylene) glycol (PEG), which is also a therapeutic agent by facilitating membrane repair. The two types of particles (mPEG-Amine and mPEG-Hydrazide) have been characterized and explored for their therapeutic potential for preventing extensive oxidative stress after primary injury.

Design of silica nanoparticles for oxidative stress attenuation in neurons

246th National Meeting (2013)

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