Magnetic transducers
Embodiments herein relate to the production of biocompatible magnetic nanoparticles with a high SAR-value which produce a large amount of heat when exposed to an alternating magnetic field. The produced heat can be used among others for therapeutic purposes, in particular for combating cancer.
1. A method for the production of nanoparticles comprising the following steps:
A1) providing a composition of at least one iron-containing compound A in at least one organic solvent LM1, wherein the at least one iron-containing compound A is selected from the group consisting of iron complex compounds, iron carbonyl compounds, iron salts, organic iron compounds, and iron-sandwich-complexes, and wherein the at least one organic solvent LM1 is a high boiling solvent;
B1) heating of the composition to a temperature in the range of 50° C. to a temperature of 50° C. below the actual reaction temperature of the iron-containing compound A according to step C1 for a minimum period of 10 minutes;
C1) heating of the composition to an actual reaction temperature between 200° C. and 400° C. to obtain particles, wherein the heating step is carried out for at least 30 minutes;
D1) purifying the obtained particles, wherein the purification is performed by Soxhlet extraction;
E1) suspending the particles in water or an aqueous solution of an acid;
F1) adding a surface-active compound;
I1) producing a dispersion of the particles in a solvent mixture of (i) water and (ii) a solvent miscible with water; and
J1) adding an alkoxysilane to the dispersion of the particles in the solvent mixture according to step I1);
wherein the method further comprising step X2) following steps C1 or E1 or F1 or I1 or J1: X2) oxidizing the formed particles by suspending the particles in 0.5 to 2M HNO3, adding an Fe(III) salt and boiling the particles under reflux; and
wherein the nanoparticles have a specific absorption rate (SAR) of 10-40 W per g Fe at a field strength of 4 kA/m and at frequency of an alternating magnetic field of 100 kHz.
2. The method according to claim 1 , further comprising step A2) following step A1:
A2) adding an additive selected from the group consisting of: tensides, silanes, Si- or Al-containing organic compounds, phosphines, saturated or unsaturated fatty acids, amines, diamines, carboxylic acids and salts thereof, saturated and unsaturated fatty acids, and polymers.
3. The method according to claim 1 , further comprising step B2) following step B1:
B2) adding an additive selected from the group consisting of: tensides, silanes, Si- or Al-containing organic compounds, phosphines, saturated or unsaturated fatty acids, amines, diamines, carboxylic acids and salts thereof, saturated and unsaturated fatty acids, and polymers,
or
B2) adding a composition of at least one iron-containing compound B in at least one organic solvent LM2, wherein the at least one iron-containing compound B is selected from the group consisting of: iron complex compounds, iron carbonyl compounds, iron salts, organic iron compounds, and iron-sandwich-complexes, and wherein the at least one organic solvent LM2 is a high boiling solvent, or
B2) adding a composition of at least one iron-containing compound B in at least one organic solvent LM2, and addition of an additive selected from the group consisting of: tensides, silanes, Si- or M-containing organic compounds, phosphines, saturated or unsaturated fatty acids, amines, diamines, carboxylic acids and salts thereof, saturated and unsaturated fatty acids, and polymers.
4. The method according to claim 3 , wherein the at least one solvent LM2 has a minimum boiling point of 200° C.
5. The method according to claim 3 , wherein the at least one solvent LM2 is selected from the group consisting of: high-boiling amines, alkanes, olefms, alcohols or ethers, alkylene glycol monoethers, alkylene glycol diethers, ethylene glycol monoethers, ethylene glycol diethers, propylene glycol monothers, propylene glycol diethers, glycerin monoethers, glycerin diethers, glycerin triethers, and glycol diethers (glymes).
6. The method according to claim 3 , wherein the at least one iron-containing compound B is identical to the at least one iron-containing compound A and/or the at least one organic solvent LM1 is identical to the at least one organic solvent LM2.
7. The method according to claim 1 , further comprising a tempering step D1*) following step D1:
D1*) tempering of the obtained particles in high boiling solvents at up to 400° C. for 1-30 hours.
8. The method according to claim 1 , wherein the at least one iron-containing compound A is selected from the group consisting of: iron complex compounds, iron carbonyl compounds, iron salts, organic iron compounds, iron salts of saturated/unsaturated fatty acids and iron-sandwich-complexes.
9. The method according to claim 1 , wherein the at least one solvent has a minimum boiling point of 200° C.
10. The method according to claim 1 , wherein the at least one solvent LM1 is selected from the group consisting of: high-boiling amines, alkanes, olefins, alcohols, ethers, alkylene glycol-monoethers, alkylene glycol-diethers, ethylene glycol-monoethers, ethylene glycol- diethers, propylene glycol-monothers, propylene glycol diethers, glycerin monoethers, glycerin diethers, glycerin triethers, and glycol diethers (glymes).
11. The method according to claim 1 , wherein the aqueous solution of the acid has a pH of 2 to 6.
12. The method according to claim 1 , wherein the acid according to step E1) is a mineral acid selected from the group consisting of: hydrochloric acid, phosphoric acid, sulfuric acid, bromhydric acid, boric acid and nitric acid.
13. The method according to claim 1 , wherein the surface-active compound according to step F1) is selected from the group consisting of: fatty acids, fatty acid salts, tensides, polymers, polyvinyl alcohol, polyethylene glycol, polyacrylic acid, dextran, PLGA, chitosan and polyethylene imine.
14. The method according to claim 1 , wherein the solvent mixture according to step I1) is an alcohol-water mixture with a volume ratio of alcohol to water ranging from 1:1 to 1:5.
15. The method according to claim 14 , wherein the solvent mixture further comprises an amine or ammonia.
16. The method according to claim 14 , wherein the alcohol is selected from the group consisting of: methanol, ethanol, propanol and isopropanol.
17. The method according to claim 1 , wherein the alkoxysilane according to step J1) is selected from the group consisting of: tetraalkoxysilanes, trialkoxysilanes, dialkoxysilanes and monoalkoxysilanes.
18. The method according to claim 1 , wherein the molar ratio of particle to alkoxysilane according to step J1) ranges from 1:1 to 1:5.
19. The method according to claim 1 , wherein the alkoxysilane according to step J1) is added under ultrasonic treatment.
20. The method according to claim 1 , wherein the dispersion obtained according to claim J1) is treated with ultrasound for 1 to 8 hours.
21. The method according to claim 1 , further comprising step L1):
L1) Coupling of an anticancer compound, a monoclonal antibody, an aptamer, a nucleic acid, an amino acid, a peptide, a protein, a carbohydrate, a lipid, a glycoprotein, a glycan, a lipoprotein, or of an anti-proliferative, anti-migrative, anti-angiogenic, anti-thrombotic, anti-inflammatory, anti-phlogistic, cytostatic, cytotoxic, anti-coagulative, anti-bacterial, anti-viral, or anti-mycotic drug to the particles obtained.
22. The method according to claim 1 , further comprising a tempering step D2*) following step X2:
D2*) tempering of the obtained particles.
23. The method according to claim 1 , further comprising step G1) following step F1: G1) treating the aqueous solution according to step F1) with ultrasound.
24. The method according to claim 23 , further comprising step H1) following step G1: H1) purifying the aqueous dispersion of the particles obtained according to step G1.
25. The method according to claim 1 , further comprising step K1) following step J1: K1) purifying of the particles.
26. The method according to claim 1 , further comprising:
(a) step D1) following step C1: D1) purifying the obtained particles;
(b) step G1) following step F1: G1) treating the aqueous solution according to step F1) with ultrasound;
(c) step H1) following step G1: H1) purifying the aqueous dispersion of the particles obtained according to step G1; and
(d) step K1) following step J1: K1) purifying of the particles.
27. The method according to claim 1 , wherein the Fe(III) salt is selected from the group consisting of Fe(NO 3 ) 3 , FeCl 3 and FePO 4 .
28. The method according to claim 1 , wherein in step B1) the composition is heated at a temperature of 100-150° C. for a minimum period of 30 minutes.
29. The method according to claim 1 , wherein the heating according to step C1) is carried out over a minimum period of 10 hours.