Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-29T07:41:48.083Z Has data issue: false hasContentIssue false
  • English
  • Français

Sonochemically Produced Hemoglobin Microbubbles

Published online by Cambridge University Press:  15 February 2011

Mike Wong  and
Kenneth S. Suslick
Mike Wong
Affiliation:
School of Chemical Sciences, University of Illinois at Urbana-Champaign, 505 S. Mathews Ave., Urbana, IL 61801
Kenneth S. Suslick
Affiliation:
School of Chemical Sciences, University of Illinois at Urbana-Champaign, 505 S. Mathews Ave., Urbana, IL 61801
Get access

Abstract

Using high-intensity ultrasound, we have developed a method for the synthesis of airfilled hemoglobin (Hb) microbubbles (≈2.5 μm in diameter). Transmission electron, scanning electron, and optical microscopy show spherical particles with a shell thickness of approximately 35 nm, or roughly six protein molecules thick. The mechanism of microbubbles formation has been determined to involve both the dispersion of gas into micron-sized bubbles and the chemical cross-linking of cysteine residues between protein molecules. The primary oxidizing agent is superoxide (HO2), which is sonochemically produced from oxygen and water during acoustic cavitation. The Hb microbubbles possess many of the desired characteristics of a blood substitute. The microbubbles are smaller than red blood cells and will not block capillaries. The microbubbles are air-filled and provide a large O2 carrying capacity. The hemoglobins of the microbubbles retain their ability to bind oxygen reversibly. In addition, the oxygen affinities are similar to those of native Hb. Even more surprisingly, microbubbles show extensive cooperativity, as indicated by Hill coefficients as high as 18, which means that in the microbubble shell, there is communication between several of the crosslinked Hb tetramers upon binding oxygen. The Hb microbubbles show minimal degradation (>25%) after storage for six months at 4 °C.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 372: Symposium W1 – Hollow and Solid Spheres and Microspheres--Science and Technology , 1994 , 89
Copyright
Copyright © Materials Research Society 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Suslick, K.S. and Grinstaff, M.W., J. Am. Chem. Soc. 112, 7807 (1990); Proc. Natl. Acad. Sci. USA 88, 7708 (1990).Google Scholar
2. Suslick, K.S., Grinstaff, M.W., Kolbeck, K.J., Wong, M., Ultrason. Sonochem. 1, S65 (1994).Google Scholar
3. Geyer, R.F., Blood Substitutes, ed. Chang, T.M.S., Geyer, R.F. (Marcel Dekker, NY, 1989), p. 31.Google Scholar
4. Winslow, R. M., Hemoglobin-Based Red Cell Substitutes, (John Hopkins University Press, Baltimore, 1991) p. 6.Google Scholar
5. Sheffield, C.L., Biotech. Appl. Biochem. 14, 249 (1991).Google Scholar
6. Looker, D., Abbot-Brown, D., Cozart, P., Durfee, S., Hoffman, S., Mathews, A.J., Miller-Roehrich, J., Shoemaker, S., Trimble, S., Fermi, G., Komiyama, N.H., Nagai, K., Stetler, G.L., Nature 356, 258 (1992).Google Scholar
7. Pool, R., Science 250, 1655 (1990).Google Scholar
8. Lowe, K.C., Washington, C., Nature 358, 717 (1992).Google Scholar
9. Otto, B.R., Verweig-van-Vught, A.M.J.J., MacLaren, D.M., Nature 358, 23 (1992).Google Scholar
10. Vandegriff, K.D., Winslow, R.M., Chem. Ind. 14, 497 (1991).Google Scholar
11. Ogden, J.E., Trends Biotech. 10, 91 (1992).Google Scholar
12. Ascenzi, P., Bertollini, A., Coletta, M., Desider, A., Giardina, B., Polizio, F., Santucci, R., Scatena, R., Amiconi, G., Inog. Biochem. 50, 263 (1993).Google Scholar
13. Hyashi, A., Suzuki, T., Shin, M., Biochim. Biophys. Acta 310, 309 (1973).Google Scholar
14. Imai, K., Morimoto, H., Kotani, M., Watari, H., Hirata, W., Kuroda, M., Biochim. Biophys. Acta 200, 189 (1970).Google Scholar
15. Stryer, L., Biochemistry., (Freeman, W.H., New York, 1988), p. 151.Google Scholar
16. Rooney, J.A., in Ultrasound: Its Chemical, Physical, and Biological Effects, ed. Suslick, K.S. (VCH, New York, 1988), p. 74.Google Scholar
17. Suslick, K.S., Science 247, 1439 (1990).Google Scholar
18. Makino, K., Mossobo, M.M., Riez, P., J. Phys. Chem. 87, 1369 (1983).Google Scholar
19. Riesz, P., Berdahl, D., Christman, C.L., Environ. Health Perspect 64, 2333 (1985).Google Scholar
20. Weissler, A., J. Am. Chem. Soc. 81, 1077 (1959).Google Scholar
21. Felton, R.H., in The Porphyrins, ed. Dolphin, D. (Academic Press, N.Y., 1978) p. 111.Google Scholar
22. Fee, J.A., in Metal Ion Activation of Dioxygen, ed. Spiro, T.G. (Wiley, N.Y., 1980) p. 209.Google Scholar
23. Asada, K., Kanematsu, S., Agr. Biol. Chem. 40, 1891 (1976).Google Scholar
24. Bronskaya, L.M., El'piner, I.Y., Biophys. 8, 344 (1963).Google Scholar
25. Jocelyn, P.C., Biochemistry of the SH Group, (Academic Press, New York, 1976).Google Scholar
26. Imai, K., Allosteric Effectors in Hemoglobin, (Cambridge Univ. Press, Cambridge, 1982).Google Scholar
27. Chemow, B., The Pharmacological Approach to the Critically Ill Patient, 2nd ed. (Williams and Wilkins, Baltimore, 1988) p. 282.Google Scholar
28. Roughton, F.J.W., Severingham, J.W., J. Appl. Physiol. 35, 861 (1973).Google Scholar