Magnetic nanoparticle compositions, and methods related thereto
Disclosed are biocompatible magnetic nanoparticle compositions for various therapeutic or biological applications, and methods related thereto. Specifically, the present invention pertains to magnetic nanoparticle compositions prepared via high-pressure homogenization processes that include a turbulent flow zone. The methods of production may involve a two-step or a one-step process. The disclosed magnetic nanoparticle compositions may be useful in the treatment of the body, body part, tissue, cell, or body fluid of a subject for a variety of indications. The disclosed magnetic nanoparticle compositions may also be useful in the fixation, separation, transportation, marking or coding of targets, or energy transformation processes.
1 . A method for preparing a magnetic nanoparticle composition, comprising:
a. generating a metal-containing magnetic material by processing a preformed metal-containing magnetic material through a turbulent flow zone in a first step, and generating a magnetic nanoparticle composition using the resulting improved magnetic material of the first step and a biocompatible coating material, via a turbulent flow zone, in a second step; or
b. generating a metal-containing magnetic material from a metal-containing solution via a turbulent flow zone in a first step, and generating a magnetic nanoparticle composition using the resulting magnetic material of the first step and a biocompatible coating material, via a turbulent flow zone, in a second step; or
c. forming a magnetic nanoparticle composition by generating a metal-containing magnetic material from a metal-containing solution and processing it with a biocompatible coating material, via a turbulent flow zone, in a single step.
2 . A method according to claim 1 , wherein in the first and the second steps are carried out in a liquid medium comprising water, or an aqueous alkaline solution having an ammonia sodium or potassium hydroxide basis.
3 . A method according to claim 1 , wherein the preformed metal-containing magnetic material comprises one or a combination of two or more of a) different metals, b) different metal compounds, c) metal with different valences, or d) any combination thereof.
4 . A method according to claim 3 , wherein the preformed metal-containing magnetic material comprises a combination of Fe-(II) and Fe-(III) in a molar ratio of 1:1 to 1:2.
5 . A method according to claim 1 , wherein the metal-containing solution is prepared from a metal, metal salt, metal alkoxyde, metal hydroxide, metal oxide, metal oxide-hydrate, metallic alloy of two or more metals, or any combination thereof.
6 . A method according to claim 5 , wherein the metal-containing solution comprises a combination of Fe-(II) and Fe-(III) salts in a molar ratio of 1:1 to 1:2.
7 . A method according to claim 1 , wherein the generated metal-containing magnetic material comprises a metal, metal salt, metal alkoxyde, metal hydroxide, metal oxide, metal oxide-hydrate, metallic alloy of two or more metals, or any combination thereof.
8 . A method according to claim 7 , wherein the metal oxide is iron oxide.
9 . A method according to claim 8 , wherein the iron oxide is magnetite, hematite, maghemite, or any combination thereof.
10 . A method according to claim 8 , wherein the iron oxide is doped with bi- or tri-valent metal ions.
11 . A method according to claim 1 , wherein the biocompatible coating material comprises a polymer, metal compound, transfection agent, or any combination thereof.
12 . A method according to claim 11 , wherein the polymer is naturally occurring, synthetic, or semi-synthetic.
13 . A method according to claim 11 , wherein the polymer comprises at least one reactive or ionic group, or any combination thereof.
14 . A method according to claim 11 , wherein the polymer comprises a homo-polymer, a co-polymer, or a polymer-blend.
15 . A method according to claim 11 , wherein the polymer comprises a biological material.
16 . A method according to claim 15 , wherein the polymer comprises a polysaccharide, polyamino acid, protein, lipid, fatty acid, heparin, heparin sulfate, chondroitin sulfate, chitin, chitosan, alginate, glycosaminoglycan, cellulose, starch, histidine-containing polymer, hydrogel polymer, any derivative thereof, or any combination thereof.
17 . A method according to claim 16 , wherein the polysaccharide is dextran.
18 . A method according to claim 17 , wherein the dextran comprises one or more functional groups.
19 . A method according to claim 12 , wherein the synthetic polymer comprises a polyvinyl compound, polyamine, polyimine, polyol, polyether, polycarboxylic acid, polysilicic acid, polyacrylate, polysiloxane, polyalkylene glycol, parylene, polylactic acid, polyglycolic acid, or any derivative thereof, or any combination thereof.
20 . A method according to claim 2 , wherein the first and the second steps are processed in a liquid carrier medium at a pressure above 100 bar.
21 . A method according to claim 2 , wherein the first and the second steps are processed in a liquid carrier medium at a pressure above 1000 bar.
22 . A method according to claim 1 , wherein the first and the second steps are processed in a liquid carrier medium at a temperature in the range from about 40° C. and the boiling point of the medium.
23 . A method according to claim 1 , wherein the first and the second steps are processed in a liquid carrier medium at a temperature in the range from about 75° C. to about 95° C.
24 . A method according to claim 1 , wherein the components are processed at a flow rate in the range from about 20 ml/min to about 200 ml/min through a turbulent flow zone in each step.
25 . A method according to claim 2 , wherein the resulting magnetic nanoparticles form a stable aqueous colloid.
26 . A method according to claim 2 , wherein the resulting magnetic nanoparticles form a stable colloid in physiological solution.
27 . A method according to claim 2 , wherein the resulting magnetic nanoparticles are separated from the carrier medium via an external magnetic field.
28 . A method according to claim 27 , wherein the resulting magnetic nanoparticles are separated with permanent magnets.
29 . A magnetic nanoparticle composition, comprising:
a. at least one metal-containing magnetic nanoparticle possessing a low-field magnetization when an external magnetic field is applied to the at least one magnetic nanoparticle; and
b. a suitable medium for suspending the at least one nanoparticle,
wherein the at least one nanoparticle has a hydrodynamic diameter less than 200 nm, and contains at least 50 mass percent of metal, and
wherein the at least one metal-containing magnetic nanoparticle comprises a biocompatible coating material.
30 . A magnetic nanoparticle composition according to claim 29 , wherein the external magnetic field has an amplitude in the range from about 0 to about 400 Oersted.
31 . A magnetic nanoparticle composition according to claim 29 , wherein the nanoparticle composition has a PEG density in the range from about 2 μmol/g to about 250 μmol/g.
32 . A magnetic nanoparticle composition according to claim 29 , wherein the at least one magnetic nanoparticle comprises a) a metal, b) a metal oxide, c) a metal oxide-hydrate, d) a metal hydroxide, e) a metallic two or more metals, or f) any combination thereof.
33 . A magnetic nanoparticle composition according to claim 32 , wherein the at least one magnetic nanoparticle comprises an oxide of iron.
34 . A magnetic nanoparticle composition according to claim 33 , wherein the iron oxide is magnetite, hematite, maghemite, or any combination thereof.
35 . A magnetic nanoparticle composition according to claim 33 , wherein the iron oxide is doped with bi- or tri-valent metal ions.
36 . A magnetic nanoparticle composition according to claim 29 , wherein the at least one magnetic nanoparticle has ferro-, antiferro-, ferri-, antiferri- or superparamagnetic properties.
37 . A magnetic nanoparticle composition according to claim 29 , wherein the biocompatible coating material comprises a polymer.
38 . A magnetic nanoparticle composition according to claim 37 , wherein the polymer is naturally occurring, synthetic, or semi-synthetic.
39 . A magnetic nanoparticle composition according to claim 37 , wherein the polymer comprises a homo-polymer, a co-polymer, or a polymer-blend.
40 . A magnetic nanoparticle composition according to claim 37 , wherein the polymer comprises at least one reactive or ionic group, or any combination thereof.
41 . A magnetic nanoparticle composition according to claim 37 , wherein the polymer comprises a biological material.
42 . A magnetic nanoparticle composition according to claim 37 , wherein the polymer comprises a polysaccharide, polyamino acid, protein, lipid, fatty acid, heparin, heparin sulfate, chondroitin sulfate, chitin, chitosan, alginate, glycosaminoglycan, cellulose, starch, histidine-containing polymer, hydrogel polymer, any derivative thereof, or any combination thereof.
43 . A magnetic nanoparticle composition according to claim 42 , wherein the polysaccharide is dextran.
44 . A magnetic nanoparticle composition according to claim 43 , wherein the dextran comprises one or more functional groups.
45 . A magnetic nanoparticle composition according to claim 38 , wherein the synthetic polymer comprises a polyvinyl compound, polyamine, polyimine, polyol, polyether, polycarboxylic acid, polysilicic acid, polyacrylate, polysiloxane, polyalkylene glycol, parylene, polylactic acid, polyglycolic acid, or any derivative thereof, or any combination thereof.
46 . A magnetic nanoparticle composition according to claim 29 , wherein the magnetic nanoparticle composition comprises one or more sub-structures.
47 . A magnetic nanoparticle composition according to claim 46 , wherein the sub-structures comprise at least one ligand, chelator, or a combination thereof.
48 . A magnetic nanoparticle composition according to claim 47 , wherein the at least one ligand or chelator comprises a peptide, protein, nucleic acid, enzyme, antibody, antibody fragment, or any combination thereof.
49 . A magnetic nanoparticle composition according to claim 48 , wherein the antibody is ING-1.
50 . A magnetic nanoparticle composition according to claim 46 , wherein the sub-structures comprise a bioactive substance.
51 . A magnetic nanoparticle composition according to claim 50 , wherein the bioactive substance comprises a pharmaceutical agent, peptide, lipid, biochemical factor, or any combination thereof.
52 . A magnetic nanoparticle composition produced according to the method of claim 1 .
53 . A magnetic nanoparticle composition according to claim 52 , wherein the magnetic nanoparticle composition comprises one or more sub-structures.
54 . A magnetic nanoparticle composition according to claim 29 , wherein the composition is used in the fixation, separation, transportation, marking or coding of targets, or energy transformation processes.
55 . A magnetic nanoparticle composition according to claim 54 , wherein the composition is used in the separation or purification of biomolecules, or any combination thereof.
56 . A therapeutic method according to claim 54 , wherein the composition is used in the separation, purification, or any combination thereof of nucleic acids, nucleic acid derivatives, nucleic acid fragments, proteins, protein derivatives, protein fragments, or any combination thereof.
57 . A magnetic nanoparticle composition according to claim 54 , wherein the composition is used for the sorting and purification of cells.
58 . A magnetic nanoparticle composition according to claim 54 , wherein the composition is used in radionuclide therapy.
59 . A magnetic nanoparticle composition according to claim 54 , wherein the composition is used in analytical processes or diagnostic assays.
60 . A magnetic nanoparticle composition according to claim 59 , wherein the composition is used as contrast media.
61 . A therapeutic method, comprising:
a. administering a magnetic nanoparticle composition according to claim 46 to at least a portion of the body, body part, tissue, cell, or body fluid of a subject comprising a target, and
b. administering energy to the magnetic nanoparticle composition combined with the target.
62 . A therapeutic method according to claim 61 , further comprising the step of applying an alternating magnetic field (AMF).
63 . A therapeutic method according to claim 61 , wherein the composition is administered via injection, topical application, transdermal application, orally ingestion, rectal insertion, inhalation through the mouth or nose, or any combination thereof.
64 . A therapeutic method according to claim 61 , wherein the method is utilized for the treatment of a cancer, AIDS, adverse angiogenesis, restenosis, amyloidosis, tuberculosis, multiple sclerosis, cardiovascular plaque, vascular plaque, obesity, malaria, illnesses due to viruses, or any combination thereof.
65 . A therapeutic method according to claim 61 , wherein the magnetic nanoparticles transport and release bioactive substances.
66 . A therapeutic method, comprising:
a. administering a magnetic nanoparticle composition according to claim 53 to at least a portion of the body, body part, tissue, cell, or body fluid of a subject comprising a target, and
b. administering energy to the magnetic nanoparticle composition combined with the target.