title: A true theranostic approach to medicine: towards tandem sensor detection and removal of endotoxin in blood.
abstract: Sepsis is one of the leading causes of death around the world. The condition occurs when a local infection overcomes the host natural defense mechanism and suddenly spreads into the circulatory system, triggering a vigorous, self-injurious inflammatory host response. The pathogenesis of sepsis is relatively well known, one of the most potent immuno-activator being bacterial lipopolysaccharide (LPS) - also known as 'endotoxin'. Tests exist to detect endotoxin in bodily fluids, but are expensive, not necessarily user-friendly and require reporter molecules. In addition, the situation for safe and effective anti-endotoxin therapy is problematical. At the present time, endotoxin removal through cartridge hemoperfusion is one of the better alternatives to combat sepsis. The capability to both measure endotoxemia levels and offer an adapted response treatment in a timely manner is crucial for better management and improved prognosis, but is currently unavailable. In this context, we describe herein preliminary research towards the development of an alternative LPS biosensor and an innovative LPS neutralization cartridge to be eventually combined in an all-integrated configuration for the theranostic, personalized treatment of blood endotoxemia/sepsis. LPS detection is performed in a real-time and label-free manner in full human blood plasma, using ultra-high frequency acoustic wave sensing in combination with ultrathin, oligoethylene glycol-based mixed surface chemistry imposed on piezoelectric quartz discs. Biosensing platforms are functionalized with polymyxin B (PMB), a cyclic peptide antibiotic with high affinity for LPS. Analogous surface modification is used on glass beads for the therapeutic cartridge component of the combined strategy. Incubation of LPS-spiked whole blood with PMB-bead chemistry resulted in a significant decrease in the production of pro-inflammatory TNF-α cytokine. LPS neutralization is discussed in relation to the perturbation of its supramolecular chemistry in solution.
authors: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6; Econous Systems Inc., 80 St. George Street, Toronto, Ontario, Canada M5S 3H6. Electronic address: mikethom@chem.utoronto.ca.
authors: Michael
authors: M
authors: Thompson
authors: Econous Systems Inc., 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
authors: Christophe
authors: C
authors: Blaszykowski
authors: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
authors: Sonia
authors: S
authors: Sheikh
authors: Clinical Biochemistry, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8.
authors: Alexander
authors: A
authors: Romaschin
mesh_terms: D015374:Biosensing Techniques; D004731:Endotoxins / Q000097:blood / Q000302:isolation & purification* / Q000633:toxicity; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood / Q000302:isolation & purification* / Q000633:toxicity; D011112:Polymyxin B / Q000008:administration & dosage* / Q000737:chemistry; D057285:Precision Medicine; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B
keywords: Electromagnetic piezoelectric acoustic sensor (EMPAS); Endotoxemia; Lipopolysaccharide (LPS); Polymyxin B (PMB); Sepsis; Theranostics