A New Aids Therapy Approach Using Magnetoliposomes

  • Detlef Müller-Schulte
  • Frank Füssl
  • Heiko Lueken
  • Marcel De Cuyper


A new concept for the treatment of the AIDS infection is described whereby a simple heat treatment is used to irreversibly inactivate the AIDS virus. The temperatures of more than 50°C required for the virus inactivation are achieved by inductively heating magnetoliposomes (ML) designed for in vivo administration. To ensure that the heat is transferred solely to the HIV and not to the adjacent tissue, the ML are pre-coated with CD4 receptor molecules, thus enabling a close attachment of the ML to the HIV via its gp 120 envelope protein. This process corresponds to the in vivo HIV infection pathway. To assess the feasibility of the new approach, serum albumin and IgG were used as model proteins for the CD4 receptor and successfully coupled to ML. Induction heating experiments with diverse ML suspensions and magnetic colloids clearly demonstrated that the magnetic particles can be selectively heated up to the required temperatures.


Human Immunodeficiency Virus Type Lauric Acid Magnetic Fluid Inductive Heating Chromotropic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Johnston MI and McGowan JJ (1992). Strategies and Progress in the Development of Antiviral Agents. in AIDS 3rd Ed., DeVita VT, Hellman S, Rosenberg SA (Eds), Philadelphia, JB Lippincott, 357–371.Google Scholar
  2. 2.
    Perelson AS, Neumann A, Markowitz M et al (1996). HIV-1 dynamics in vivo: Virion clearance rate, infected cell life-span, and viral generation time. Science 271 1582–1586.ADSCrossRefGoogle Scholar
  3. 3.
    Shirasaka T, Kavlick MF, Ueno T et al (1995). Emergence of human immunodeficiency virus type I variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Nat. Acad. Sci. 92, 2398–2402.ADSCrossRefGoogle Scholar
  4. 4.
    Narrer T (1995). HIV and AIDS. In Medizinische Immunologie. Baenkler (Ed), Landsberg/Lech, Ecomed Verlagsgesellschaft, 1–36.Google Scholar
  5. 5.
    Moutouh L, Corbeil J and Richman DD (1996). Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure. Proc. Nat. Acad. Sci. 93 6106–6111.ADSCrossRefGoogle Scholar
  6. 6.
    Lane HC and Kovacs JA (1994). Interleukin-2 as therapy for HIV disease. The New England Journal of Medicine 333 193.Google Scholar
  7. 7.
    Baier M, Werner A, Barmen N et al (1996). HIV suppression by interleukin-16. Nature 378 563.ADSCrossRefGoogle Scholar
  8. 8.
    McElrath MJ, Corey L, Greenberg PD et al (1996). Human immunodeficiency virus type 1 infection despite prior immunization with a recombinant envelope vaccine regimen. Proc. Nat. Acad. Sci. 93 3972–3977.ADSCrossRefGoogle Scholar
  9. 9.
    Fuxman YL (1993). On the mechanism of HIV disease: a hypothesis and the anti-AIDS therapy it suggests. Medical Hypothesis 41 467–469.CrossRefGoogle Scholar
  10. 10.
    AIDS Etiology, Diagnosis, Treatment and Prevention (1992). DeVita VT, Hellman S and Rosenberg SA (Eds), Philadelphia, JB Lippincott, 3rd Edition.Google Scholar
  11. 11.
    Walker BD (1994). The rationale for immunotherapy in HIV-1 infection. Journal of Acquired Immune Deficiency Syndrome 7 S6–S13.Google Scholar
  12. 12.
    Bour S, Geleziunas R and Wainberg MA (1995). The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiological Reviews 59 63–93.Google Scholar
  13. 13.
    Wong GHW, McHugh T, Weber R and Goeddel DV (1991). Tumor necrosis factor a selectively sensitizes human immunodeficiency virus infected cells to heat and radiation. Proc. Nat. Acad. Sci. 88 4372–4376.ADSCrossRefGoogle Scholar
  14. 14.
    Martin LS, McDougal JS and Loskoski SL (1985). Disinfection and inactivation of the human T lymphotropic virus type III/lymphadenopathy-associated virus. The Journal of Infectious Diseases 152 400–403.CrossRefGoogle Scholar
  15. 15.
    Müller-Schulte D, Füssl F, Lueken H and De Cuyper M (1995). Neuer Ansatz für die AIDS-Therpie unter Verwendung superparamagnetischer Nanopartikel. In Alma Mater Aquensis Band XXXI, University Aachen (Ed), 174–187.Google Scholar
  16. 16.
    Müller-Schulte D (1995). Mittel zur selektiven AIDS Therapy sowie Verfahren zur Herstellung und Verwendung derselben. German Patent DE 4412651.Google Scholar
  17. 17.
    Franconi C, Raganella L, Tiberio CA and Begnozzi L (1991). Low frequency RF hyperthermia; IV-A 27 MHz hybrid applicator for localized deep tumor heating. IEEE Transactions on Biomedical Engineering 38, 287–293.CrossRefGoogle Scholar
  18. 18.
    Lee CA, Phillips AN, Elford J et al (1992). Applications of CD4 counts in a cohort of HIV-1 seropositive patients with haemophilia. In Immunodeficiency in HIV infection and AIDS. Janossy G, Autran B and Miedema F (Eds), Windsor, Surrey, Karger, 32–46.Google Scholar
  19. 19.
    Shinkai M, Suzuki M, lijima S and Kobayashi T (1994). Antibody-conjugated magnetoliposomes for targeting cancer cells and their application in hyperthermia. Biotechnology and Applied Biochemistry 21 125–137.Google Scholar
  20. 20.
    Masuko Y, Tazawa K, Viroochatapan E et al (1995). Possibility of thermosensitive magnetoliposomes as new agent for electromagnetic induced hyperthermia. Biological Pharmaceutical Bulletin 18 1802–1804.CrossRefGoogle Scholar
  21. 21.
    Gordon RT (1987). Use of magnetic susceptibility probes in the treatment of cancer. U.S. Patent 4,662,359.Google Scholar
  22. 22.
    Jordan A, Wust P, Fähling H et al (1993). Inductive heating offerrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia. International Journal of Hyperthermia 9, 51–68.CrossRefGoogle Scholar
  23. 23.
    Litzinger DC, Buiting AMJ, van Rooijen and Huang L (1994). Effect of liposome size on the circulation time and intraorgan distribution ofamphipathic poly(ethylene glycol)-containing liposomes. Biochimica et Biophysica Acta 1190 99–107.CrossRefGoogle Scholar
  24. 24.
    Reimers GW and Khalafalla (1974). Production of magnetic fluids by peptization techniques. US Patent 3,843,540.Google Scholar
  25. 25.
    De Cuyper M and Joniau M (1990). Potentialities of magnetoliposomes in studying symmetric and asymmetric phospholipid transfer processes. Biochimica et Biophysica. Acta 1027 172–178.CrossRefGoogle Scholar
  26. 26.
    De Cuyper M and Joniau M (1988). Magnetoliposomes formation and structural charaterization. European Biophysics Journal 15 311–319.Google Scholar
  27. 27.
    De Cuyper M and Joniau M (1991). Mechanistic aspect of the adsorption ofphospholipids onto lauric acid stabilized. Fe nanocolloids. Langmuir 7 647–652.CrossRefGoogle Scholar
  28. 28.
    De Cuyper M (1996). Applications of magnetoproteoliposomes in bioreactors operating in high-gradient magnetic field. In Handbook of Nonmedical Applications of Liposomes Vol III. Barenholz Y and Lasic DD (Eds), Boca Raton, CRC Press Inc, 323–340.Google Scholar
  29. 29.
    Gabizon A and Papahadjopoulos D (1988). Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc. Nat. Acad. Sci. 85 6949–6953.ADSCrossRefGoogle Scholar
  30. 30.
    Woodle MC, Matthay KK, Newman et al (1992). Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. Biochimica et Biophysica Acta 1105 193–200.CrossRefGoogle Scholar
  31. 31.
    Allen TM, Austin GA, Chonn A et al (1991). Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size. Biochimica et Biophysica Acta 1061 56–64.CrossRefGoogle Scholar
  32. 32.
    De Cuyper M and Noppe W (1996). Extractability of the phospholipid envelope of magnetoliposomes by organic solvents. Journal of Colloid and Interface Science 182 478–482.CrossRefGoogle Scholar
  33. 33.
    Yaacob II, Nunes AC, Bose A et al (1994). Synthesis and characterization of magnetic nanoparticles in spontaneously generated vesicles. Journal of Colloid and Interface Science 168 289–301.CrossRefGoogle Scholar
  34. 34.
    Yaacob II, Nunes AC and Bose A (1995). Magnetic nanoparticles produced in spontaneous cationic-anionic vesicles; room temperature synthesis and characterization. Journal of Colloid and Interface Science 171 73–84.CrossRefGoogle Scholar
  35. 35.
    Mann S and Hannington JP (1988). Formation of iron oxides in unilamellar vesicles. Journal of Colloid and Interface Science 122 326–335.CrossRefGoogle Scholar
  36. 36.
    Bogdanov AA, Martin C, Weissleder R et al (1994). Trapping of dextran-coated colloids in liposomes by transient binding to aminophospholipid: preparation of ferrosomes. Biochimica et Biophysica Acta 1193 212–218.CrossRefGoogle Scholar
  37. 37.
    Viroonchatapan E, Ueno M, Sato H et al (1995). Preparation and characterization of dextran magnetite-incorporated thermosensitive liposomes: an on-line flow system for quantifying magnetic responsiveness. Pharmaceutical Research 12 1176–1183.CrossRefGoogle Scholar
  38. 38.
    Menager C and Cabuil V (1995). Synthesis of magnetic liposomes. Journal of Colloid and Interface Science 169 251–253.CrossRefGoogle Scholar
  39. 39.
    Weissleder R, Bogdanov AA, Neuwelt EA et al (1995). Long circulating iron oxides for MR imaging. Advances in Drug Delivery Review 16 321–334.CrossRefGoogle Scholar
  40. 40.
    Flasher D, Konopka K, Chamow SW et al (1994). Liposome targeting to human immunodeficiency virus type 1-infected cells via recombinant soluble CD4 and CD4 immunoadhesin (CD4-IgG). Biochimica et Biophysica Acta 1194 185–196.CrossRefGoogle Scholar
  41. 41.
    Hansen CB, Kao GY, Moase EH et al (1995). Attachment of antibodies to sterically stabilized liposomes: evaluation, comparison and optimization of coupling procedures. Biochimica et Biophysica Acta 1239 133–144.CrossRefGoogle Scholar
  42. 42.
    Heath TD, Macher BA and Papahadjopoulos D (1981). Covalent attachment of immunoglobulins to liposomes via glycosphingolipids. Biochimica et Biophysica Acta 649 66–81.CrossRefGoogle Scholar
  43. 43.
    Lentz RR, Alford DR and Dombrose FA (1980). Determination of Phosphatidylglycerol asymmetry in small, unilamellar vesicles by chemical modification. Biochemistry 19 2555–2559.CrossRefGoogle Scholar
  44. 44.
    Smith PK, Krohn RI, Hermanson GT et al (1985). Measurement of protein using bicinchoninic acid. Analytical Biochemistry 150 76–85.CrossRefGoogle Scholar
  45. 45.
    Chan DCF, Kirpotin DB and Bunn PA (1993). Synthesis and evaluation of colloid magnetic iron oxides for the site-specific radiofrequency-induced hyperthermia of cancer. Journal of Magnetism and Magnetic Materials 122 374–378.ADSCrossRefGoogle Scholar
  46. 46.
    Kittel C (1989). In Einführung in die Festkörperphysik. München,Wien, R. Oldenburg Verlag, 455–527.Google Scholar
  47. 47.
    Hanson M (1991). The frequency dependence of the complex susceptibility of magnetic fluids. Journal of Magnetism and Magnetic Materials. 96 105–113.ADSCrossRefGoogle Scholar
  48. 48.
    Sato T and Sunamoto J (1992). Recent aspects in the use of liposomes in biotechnology and medicine. Progress in Lipid Research 31 345–372.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Detlef Müller-Schulte
    • 1
  • Frank Füssl
    • 1
  • Heiko Lueken
    • 1
  • Marcel De Cuyper
    • 2
  1. 1.Institut für Anorganische ChemieRWTH AachenAachenGermany
  2. 2.Campus KortrijkKatholieke Universiteit LeuvenKortrijkBelgium

Personalised recommendations