Core-shell hydrogel nanoparticles for low-abundance biomarker capture and amplification. Nanoparticles are engineered with a polymer shell with pore sizes constructed to eliminate high-abundance high-molecular-weight proteins from low-abundance low-molecular-weight TBI biomarkers through size sieving and high-affinity chemical bait dye molecule within the core that binds biomarkers. Due to mass action kinetics, most low-abundance protein markers exist pre-bound to high-abundance carrier proteins such as albumin that exist in billions of fold molar excess. Panel (a) Biomarkers are complexed to high-abundance proteins when nanoparticles are introduced into the saliva. Panel (b) Within seconds, the biomarkers are collected and concentrated within the nanoparticle as the high-affinity dye molecule out-competes the carrier protein for biomarker binding
A View to the Future for Nanoparticle-Based Salivary TBI Diagnostics
In addition to the potential for the saliva proteome as a new untapped archive for TBI-specific biomarkers, the use of nanoparticle-based biomarker harvesting could provide a new opportunity to characterize the potential aggregate neurodegenerative effects of chronic sub-concussive blows suffered by athletes and by soldiers in the military [71–74]. A salivary-based protein biomarker-profiling tool could provide a facile means to record an individual’s unique baseline biomarker signature and then serially track this profile for subtle changes longitudinally over time since saliva collection is so noninvasive. The result of this new opportunity could be a personalized approach to TBI diagnostics and monitoring to help clinicians determine when activity should be restricted, whether therapeutic interventions are effective, and whether the individual is ready to return to activity. In this view to the future, a baseline saliva sample could be taken at the beginning of a football player or soldier’s career and then a biomarker profile determined using nanoparticle-harvesting agents. This baseline salivary protein fingerprint could then be compared to subsequent saliva proteomic profiles measured at predetermined intervals for overall monitoring either in a pre- or post-concussion state and provide quantitative information to aid the clinician in managing any short- and long-term effects of TBI.
Emanuel Petricoin is a coinventor on issued patents relating to the nanoparticle technology described in this chapter and can receive royalties from the licenses taken. He is an equity interest holder, consultant, and cofounder of Ceres Nanosciences Inc., which has licensed the nanoparticle technology described in this chapter.
This project was made possible in part by nonrestrictive funding from the Potomac Health Foundation and the generous support of the College of Science and the College of Education and Human Development.
Mondello S, Papa L, Buki A, Bullock MR, Czeiter E, Tortella FC, Wang KK, Hayes RL. Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care. 2011;15:R156.PubMedCentralPubMedCrossRef
Marion DW. Current diagnostic and therapeutic challenges. Trauma Brain Inj. 2012:313–23.
Graham R, Rivara FP, Ford MA, Mason Spicer C. Eds. Treatment and management of prolonged symptoms and post-concussion syndrome. In: Sports-related concussions in youth: Improving the science, changing the culture. Institute of Medicine of the National Academies, The National Academies Press, Washington, DC, 2013. Available at www.iom.edu/Reports/2013/Sports-Related-Concussions-in-Youth-Improving-the-Science-Changing-the-Culture.aspx. Accessed November 13, 2013
Diaz-Arrastia R, Kochanek PM, Bergold P, Kenney K, Marx C, Grimes J, Loh Y, Adam G, Oskvig DB, Curley K. Pharmacotherapy of traumatic brain injury: state of the science and the road forward report of the Department of Defense Neurotrauma Pharmacology Workgroup. J Neurotrauma. 2013;31:135–58.CrossRef
Patel S, Shah RJ, Coleman P, Sabbagh M. Potential peripheral biomarkers for the diagnosis of Alzheimer’s disease. Int J Alzheimers Dis. 2011;2011:1–9.CrossRef