1 / 19

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.

gaetan
Download Presentation

Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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.

More Related