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Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy

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Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy Presented by: Daniel To May 3, 2007 Outline Types of Magnets How to produce nanomagnets and ... – PowerPoint PPT presentation

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Title: Magnetic Nanoparticles Applications and Bioavailability for Cancer Therapy


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 (lt20nm) 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 (lt100 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 122
  • 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_affa
irs/techbeat/tb2007_0201.htmmagnets
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
Treated Tumor
Before Treatment
Untreated Tumor
Rectum
  • Non-local heating in body is the result of
    eddy-currents
  • The currents resulting from the magnetic field
    produce heat

After Treatment
15
Magnetic Drug Delivery System
Pankhurst, et. al. 2003 J Phys D 36R167-R181.
  • 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

Dobson 2006. Drug Dev Res 6755-60. Widder, et.
al. 1978. Proc Soc Exp Biol Med 58141-146.
16
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 6755-60. Kubo, et. al.
2000 Targeted delivery of anticancer drugs
with intravenously administered magnetic
liposomes in osteosarcoma-bearing hamsters. Int
J Oncol 17309-316.
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