Nanoscale Biosensor for Detection of Reactive Oxygen Species

  • Tarl W. Prow
  • Daniel Sundh
  • Gerard A. Lutty
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1028)

Abstract

Noninvasive detection of biological responses to reactive oxygen species (ROS) in vivo could shed light on mechanisms at work in diverse areas like developmental dynamics, therapeutic effectiveness, drug discovery, pathogenic processes, and disease prevention. Research on ROS is usually dependent on in vitro models without translational relevance. Nanoscale (<100 nm) particulates are attractive carriers and platforms for biosensor technology due to their small size, flexible assembly, and favorable toxicity profiles. Intracellular signalling pathways activated in response to ROS have been well documented and mechanisms elaborated. Likewise, there is a wealth of genetic reporter systems that utilize fluorescent proteins capable of being monitored noninvasively. We combined these elements into a platform technology that utilizes nanoparticle-tethered synthetic genetic elements that respond to cellular response elements to report endogenous responses to oxidative insult through fluorescent gene expression. We envision the future of this technology to play a research role quantifying oxidative stress in vivo and a future clinical role as an automated theragnostic for ROS-related diseases. The production of this nanobiosensor technology utilizes off-the-shelf components and can be carried out in a molecular biology laboratory. Assessment of fluorescent protein expression can be done with noninvasive imaging and quantitative protein expression analysis. This is a flexible nanoparticle-based reporter system for monitoring in vivo responses to ROS.

Key words

Magnetic nanoparticles Reactive oxygen species Non-invasive imaging Antioxidant response element 

References

  1. 1.
    Lin L, Grice JE, Butler MK et al (2011) Time-correlated single photon counting for simultaneous monitoring of zinc oxide nanoparticles and NAD(P)H in intact and barrier disrupted volunteer skin. Pharm Res 28(11):2920–2930CrossRefGoogle Scholar
  2. 2.
    Monteiro-Riviere NA, Wiench K, Landsiedel R, Schulte S, Inman AO, Riviere JE (2011) Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. Toxicol Sci 123(1):264–280CrossRefGoogle Scholar
  3. 3.
    Violante MR (1990) Potential of microparticles for diagnostic tracer imaging. Acta Radiol Suppl 374:153–156Google Scholar
  4. 4.
    Bernd H, De Kerviler E, Gaillard S, Bonnemain B (2009) Safety and tolerability of ultrasmall superparamagnetic iron oxide contrast agent: comprehensive analysis of a clinical development program. Invest Radiol 44:336–342CrossRefGoogle Scholar
  5. 5.
    Mahmoudi M, Hosseinkhani H, Hosseinkhani M et al (2011) Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. Chem Rev 111:253–280CrossRefGoogle Scholar
  6. 6.
    Grutzkau A, Radbruch A (2010) Small but mighty: how the MACS-technology based on nanosized superparamagnetic particles has helped to analyze the immune system within the last 20 years. Cytometry A 77:643–647Google Scholar
  7. 7.
    Prow TW, Kotov NA, Lvov YM, Rijnbrand R, Leary JF (2004) Nanoparticles, molecular biosensors, and multispectral confocal microscopy. J Mol Histol 35:555–564CrossRefGoogle Scholar
  8. 8.
    Prow T, Grebe R, Merges C et al (2006) Nanoparticle tethered antioxidant response element as a biosensor for oxygen induced toxicity in retinal endothelial cells. Mol Vis 12:616–625Google Scholar
  9. 9.
    Prow T, Smith JN, Grebe R et al (2006) Construction, gene delivery, and expression of DNA tethered nanoparticles. Mol Vis 12:606–615Google Scholar
  10. 10.
    Prow TW (2010) Toxicity of nanomaterials to the eye. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2:317–333CrossRefGoogle Scholar
  11. 11.
    Prow TW, Bhutto I, Kim SY et al (2008) Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium. Nanomedicine 4:340–349CrossRefGoogle Scholar
  12. 12.
    Prow TW, Bhutto I, Grebe R et al (2008) Nanoparticle-delivered biosensor for reactive oxygen species in diabetes. Vision Res 48:478–485CrossRefGoogle Scholar
  13. 13.
    Bergua A, Mayer B, Neuhuber WL (1996) Nitrergic and VIPergic neurons in the choroid and ciliary ganglion of the duck Anis carina. Anat Embryol (Berl) 193:239–248CrossRefGoogle Scholar
  14. 14.
    Brownlee M (2003) A radical explanation for glucose-induced beta cell dysfunction. J Clin Invest 112:1788–1790Google Scholar
  15. 15.
    Giardino I, Edelstein D, Brownlee M (1996) BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells. J Clin Invest 97:1422–1428CrossRefGoogle Scholar
  16. 16.
    Wiernsperger NF (2003) Oxidative stress as a therapeutic target in diabetes: revisiting the controversy. Diabetes Metab 29:579–585CrossRefGoogle Scholar
  17. 17.
    Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115–134CrossRefGoogle Scholar
  18. 18.
    Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefGoogle Scholar
  19. 19.
    Cory JG, Szentivanyi A (1987) Cancer biology and therapeutics. Plenum, New YorkCrossRefGoogle Scholar
  20. 20.
    Prochaska HJ, De Long MJ, Talalay P (1985) On the mechanisms of induction of cancer-protective enzymes: a unifying proposal. Proc Natl Acad Sci USA 82:8232–8236CrossRefGoogle Scholar
  21. 21.
    Prochaska HJ, Talalay P (1988) Regulatory mechanisms of monofunctional and bifunctional anticarcinogenic enzyme inducers in murine liver. Cancer Res 48:4776–4782Google Scholar
  22. 22.
    Friling RS, Bergelson S, Daniel V (1992) Two adjacent AP-1-like binding sites form the electrophile-responsive element of the murine glutathione S-transferase Ya subunit gene. Proc Natl Acad Sci USA 89:668–672CrossRefGoogle Scholar
  23. 23.
    Wasserman WW, Fahl WE (1997) Functional antioxidant responsive elements. Proc Natl Acad Sci USA 94:5361–5366CrossRefGoogle Scholar
  24. 24.
    Zhu M, Fahl WE (2000) Development of a green fluorescent protein microplate assay for the screening of chemopreventive agents. Anal Biochem 287:210–217CrossRefGoogle Scholar
  25. 25.
    Zhu M, Fahl WE (2001) Functional characterization of transcription regulators that interact with the electrophile response element. Biochem Biophys Res Commun 289:212–219CrossRefGoogle Scholar
  26. 26.
    Zhu M, Chapman WG, Oberley MJ, Wasserman WW, Fahl WE (2001) Polymorphic electrophile response elements in the mouse glutathione S-transferase GSTa1 gene that confer increased induction. Cancer Lett 164:113–118CrossRefGoogle Scholar
  27. 27.
    Dinkova-Kostova AT, Holtzclaw WD, Cole RN et al (2002) Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci USA 99:11908–11913CrossRefGoogle Scholar
  28. 28.
    Day RM, Suzuki YJ, Fanburg BL (2003) Regulation of glutathione by oxidative stress in bovine pulmonary artery endothelial cells. Antioxid Redox Signal 5:699–704CrossRefGoogle Scholar
  29. 29.
    Jaiswal AK (2000) Regulation of genes encoding NAD(P)H:quinone oxidoreductases. Free Radic Biol Med 29:254–262CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2013

Authors and Affiliations

  • Tarl W. Prow
    • 1
  • Daniel Sundh
    • 1
  • Gerard A. Lutty
    • 2
  1. 1.Dermatology Research CentrePrincess Alexandra Hospital, School of Medicine, The University of QueenslandBrisbaneAustralia
  2. 2.Wilmer Ophthalmological InstituteJohns Hopkins HospitalBaltimoreUSA

Personalised recommendations