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Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy

Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy. Presented by: Daniel To May 3, 2007. Outline. Types of Magnets How to produce nanomagnets and make them bioavailable Cancer therapies using these bioavailable nanomagnets. Types of Magnets.

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Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy

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  1. Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy Presented by: Daniel To May 3, 2007

  2. Outline • Types of Magnets • How to produce nanomagnets and make them bioavailable • Cancer therapies using these bioavailable nanomagnets

  3. Types of Magnets • Ferromagnetic materials the magnetic moments of neighboring atoms align resulting in a net magnetic moment. • Paramagnetic materials are randomly oriented due to Brownian motion, except in the presence of external magnetic field. B

  4. Superparamagnetic • Combination of paramagnetic and ferromagnetic properties • Made of nano-sized (<20nm) ferrous • magnetic particles, but affected by Brownian Motion. • They will align in the presence of an external magnetic field. • Magnetite naturally found in human body. Hergt, Rudolf. Journal of Physics: Condensed Matter v18 2006 s2919-2934

  5. Dextran Coated Magnetite Nanoparticles • Synthesis of polysaccharide covered superparamagnetic oxide colloids (5,262,176) • For MRI imaging • FDA max size for injectables = 220 nm. • Smaller sizes (<100 nm) have longer plasma half-life. • Blood clearance by Reticuloendothelial system (RES) • Liver and Spleen • Without coating, opsonin proteins deposit on Magnetite and mark for removal by RES US Patent 5262176

  6. Formation of Nanoparticles • Solution of Dextran and Ferric hexahydrate (acidic solution) • Less Dextran Larger Particles • Drip in Ammonium hydroxide (basic) at ~2oC • Stirred at 75oC for 75 min. • Purified by washing and ultra-centrifugation • Resulting Size ~ 10-20 nm • Plasma half-life: 200 min

  7. Variation of Formation • Change Coating Material • Various other starches, Sulfated Dextran (for functionalization) • Crosslinking coating material • Increases plasma half-life • Same Particle Size

  8. Magnetite Cationic Liposomes (MCL) • Why Cationic? • Interaction between + liposome and – cell • membrane results in 10x uptake. Shinkai, Masashige. Journal of Magnetism and Magnetic Materials 194 (1999) 176-184

  9. Formation of MCL • Colloidal magnetite dispersed in distilled water • N-(a-trimethyl-amminoacetyl)-didodecyl-D-glutamate chloride (TMAG) Dilauroylphosphatidylcholine (DLPC) Dioleoylphosphatidyl-ethanolamine (DOPE) added to dispersion at ratio of 1:2:2 • Stirred and sonicated for 15 min • pH raised to 7.4 by NaCl and Na phosphate buffered and then sonicated Shinkai, Masashige. Journal of Magnetism and Magnetic Materials 194 (1999) 176-184

  10. Uses of Nano Magnets • Hyperthermia • An oscillating magnetic field on nanomagnets result in local heating by (1) hysteresis, (2) frictional losses (3) Neel or Brown relaxation • External Magnetic field for nanoparticle delivery • Magnetic nanoparticles loaded with • drug can be directed to diseased site • for Drug Delivery or MRI imaging. Hergt, Rudolf. J.Physics: Condensed Matter 18 (2006) S2919-S2934 http://www.nist.gov/public_affairs/techbeat/tb2007_0201.htm#magnets

  11. History of Nano Magnet Hyperthermia • 1957 Gilchrist first proposed the use of microparticle hyperthermia (0.01-0.1 kW/g). • 1975 internationally recognized at the first international congress on hyperthermic oncology • 1993 Jordan showed nanoparticles (~1 kW/g) release more heat than microparticles. Ito. Cancer Immunological Immunotherapy (2006) v55 320-328 Jordan. Journal of Magnetism and Magnetic Materials v201 (1999) 413-419Hergt, Rudolf. Journal of Physics: Condensed Matter v18 2006 s2919-2934

  12. Delivery Magnetic nanoparticles • Magnetite nanoparticles encapsulated in liposomes • (1) Antibody conjugated (AML) • (2) Positive Surface Charge (MCL) • Sprague-Dawley rats injected with two human tumors. • Lipsomes injected into 1 • tumor (black) and applied • Alternating Magnetic Field Ito A., Honda H., Kobayashi T. Cancer Immunol Immunother Res 2006 55; 320-328

  13. Cancer Treatment • Heating due to magnetic field results in two possibilities • Death due to overheating • Increase in heat shock • proteins result in • anti-cancer immunity. Ito A., Honda H., Kobayashi T. Cancer Immunol Immunother Res 2006 55; 320-328

  14. Effect of Hyperthermia • Non-local heating in body is the result of eddy-currents • The currents resulting from the magnetic field produce heat Treated Tumor Before Treatment Untreated Tumor Rectum After Treatment

  15. Magnetic Drug Delivery System • Using Magnetic Nanoparticles for Drug Delivery • Widder & others developed method in late 1970s • Drug loaded magnetic nanoparticles introduced through IV or IA injection and directed with External Magnets • Requires smaller dosage because of targeting, resulting in fewer side effects Pankhurst, et. al. [2003] J Phys D 36:R167-R181. Dobson [2006]. Drug Dev Res 67:55-60. Widder, et. al. [1978]. Proc Soc Exp Biol Med 58:141-146.

  16. M M M Magnetite Core M M Starch Polymer M M Magnetic Nanoparticles/Carriers • Magnetite Core • Starch Polymer Coating • Bioavailable • Phosphate in coating for functionalization • Chemo Drug attached to Coating • Mitoxantrone • Drug Delivered to Rabbit with Carcinoma R. Jurgons. Journal of Physics: Condensed Matter v 18. (2006) S2893-S2902

  17. Results of Drug Delivery • External magnetic field (dark) • deliver more nanoparticles to tumor • No magnetic field (white) • most nanoparticles in non tumor regions R. Jurgons. Journal of Physics: Condensed Matter v 18. (2006) S2893-S2902

  18. Results of Drug Delivery • No treatment (white triangle) • Growth of tumor size (ie metastases) • With Treatment (dark circle) • Complete remission • Only 20% of normal dosage R. Jurgons. Journal of Physics: Condensed Matter v 18. (2006) S2893-S2902

  19. Conclusions • Nanomagnets can be made bioavailable by liposomal encapsulation with targeting • Nanoparticles smaller than 20 nm can be useful for local heat generation • Intracellular hyperthermia kills the cancer cell and releases heat shock proteins. These are used to target and kill other cancer cells. • Results in reduction in growth of tumor size Dobson [2006] “Mangetic nanoparticles for drug delivery.” Drug Dev Res 67:55-60. Kubo, et. al. [2000] “Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters.” Int J Oncol 17:309-316.

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