Development of Nanoparticle-Enabled Protein Biomarker Discovery: Implementation for Saliva-Based Traumatic Brain Injury Detection

Fig. 6.1

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 [7174]. 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.
Schmid KE, Tortella FC. The diagnosis of traumatic brain injury on the battlefield. Front Neurol. 2012;3:90.PubMedCentralPubMedCrossRef
Jinguji TM, Bompadre V, Harmon KG, Satchell EK, Gilbert K, Wild J, Eary JF. Sport concussion assessment tool–2: baseline values for high school athletes. Br J Sports Med. 2012;46:365–70.PubMedCrossRef
Mansell JL, Tierney RT, Higgins M, McDevitt J, Toone N, Glutting J. Concussive signs and symptoms following head impacts in collegiate athletes. Brain Inj. 2010;24:1070–4.PubMedCrossRef
Chastain CA, Oyoyo UE, Zipperman M, Joo E, Ashwal S, Shutter LA, Tong KA. Predicting outcomes of traumatic brain injury by imaging modality and injury distribution. J Neurotrauma. 2009;26:1183–96.PubMedCrossRef
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
Prabhu SP. The role of neuroimaging in sport-related concussion. Clin Sports Med. 2011;30:103.PubMedCrossRef
Kumar R, Husain M, Gupta RK, Hasan KM, Haris M, Agarwal AK, Pandey CM, Narayana PA. Serial changes in the white matter diffusion tensor imaging metrics in moderate traumatic brain injury and correlation with neuro-cognitive function. J Neurotrauma. 2009;26:481–95.PubMedCrossRef
Nuwer MR, Hovda DA, Schrader LM, Vespa PM. Routine and quantitative EEG in mild traumatic brain injury. Clin Neurophysiol. 2005;116:2001–25.PubMedCrossRef
Maruta J, Suh M, Niogi SN, Mukherjee P, Ghajar J. Visual tracking synchronization as a metric for concussion screening. J Head Trauma Rehabil. 2010;25:293–305.PubMedCrossRef
Dash PK, Zhao J, Hergenroeder G, Moore AN. Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. Neurotherapeutics. 2010;7:100–14.PubMedCrossRef
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
Luchini A, Longo C, Espina V, Petricoin III EF, Liotta LA. Nanoparticle technology: addressing the fundamental roadblocks to protein biomarker discovery. J Mater Chem. 2009;19:5071–7.PubMedCentralPubMedCrossRef
Liotta LA, Petricoin EF. Omics and cancer biomarkers: link to the biological truth or bear the consequences. Cancer Epidemiol Biomarkers Prev. 2012;21:1229–35.PubMedCentralPubMedCrossRef
Casanova-Salas I, Rubio-Briones J, Fernández-Serra A, López-Guerrero JA. miRNAs as biomarkers in prostate cancer. Clin Transl Oncol. 2012;14:803–11.PubMedCrossRef
Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A. Biomarkers predicting clinical outcome of epidermal growth factor receptor–targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst. 2009;101:1308–24.PubMedCentralPubMedCrossRef
Socinski MA. The emerging role of biomarkers in advanced non–small-cell lung cancer. Clin Lung Cancer. 2010;11:149–59.PubMedCrossRef
Devic I, Hwang HJ, Edgar JS, Izutsu K, Presland R, Pan C, Goodlett DR, Wang Y, Armaly J, Tumas V. Salivary alpha-synuclein and DJ-1: potential biomarkers for Parkinson’s disease. Brain. 2011;134:e178.PubMedCentralPubMedCrossRef
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
Readnower RD, Chavko M, Adeeb S, Conroy MD, Pauly JR, McCarron RM, Sullivan PG. Increase in blood–brain barrier permeability, oxidative stress, and activated microglia in a rat model of blast-induced traumatic brain injury. J Neurosci Res. 2010;88:3530–9.PubMedCentralPubMedCrossRef
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Sep 17, 2015 | Posted by in General Dentistry | Comments Off on Development of Nanoparticle-Enabled Protein Biomarker Discovery: Implementation for Saliva-Based Traumatic Brain Injury Detection
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