Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
  • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
  • H01F1/0036—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties showing low dimensional magnetism, i.e. spin rearrangements due to a restriction of dimensions, e.g. showing giant magnetoresistivity
  • H01F1/0045—Zero dimensional, e.g. nanoparticles, soft nanoparticles for medical/biological use
  • H01F1/0054—Coated nanoparticles, e.g. nanoparticles coated with organic surfactant
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y40/00—Manufacture or treatment of nanostructures
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y25/00—Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance

Definitions

• the subject of the invention is a method for obtaining ultrafine superparamagnetic gamma iron(III) oxide nanoparticles doped with magnesium and nanoparticles produced by this method.
• Ultrafine superparamagnetic iron oxide nanoparticles are a nanomaterial with potential applications in nanomedicine, particularly in oncology treatment using magnetic hyperthermia (X. Liu, et al. Theranostics 2020, 10(8), 3793-3815; A. F. Sumser, et al. Int. J. Hyperthermia 2020, 37(1), 15-27; Y. Lu, et al. Int. J. Hyperthemia 2020, 37(3), 141-154; I. Raouf, et al. J. Therm. Biol. 2020, 91, 102644; S. Nardecchia, et al. Nanomaterials 2019, 9(2), 191; C.S.S.R. Kumar, F. Mohammad. Adv. Drug Deliv. Rev. 2011, 63(9), 789-808; B. Thiesen, A. Jordan, Int. J. Hyperthermia 2008, 24(6), 467-474).
• USPIO nanoparticles Another application of USPIO nanoparticles is known from application description US2014249413 Al as a treatment for a disease or condition associated with activated macrophages.
• the USPIO nanoparticles used are superparamagnetic iron oxide nanoparticles with diameters ranging from 1 to 50 nm, more commonly 5 to 40 nm, which are typically made of maghemite (Fe2O3) or magnetite (Fe3O4) with regions containing crystals with unpaired spins.
• maghemite Fe2O3
• Fe3O4 magnetite
• These magnetic domains are disordered in the absence of a magnetic field, but when a field is applied (i.e., during an MRI), the magnetic domains align, creating a magnetic moment much greater than the sum of the individual unpaired electrons without causing residual particle magnetization.
• USPIO nanoparticles When injected into the blood, USPIO nanoparticles are captured by macrophages and accumulate in inflamed tissues
• USPIO nanoparticles obtained by co-precipitation method starting from precursors of iron(II) and iron(III) salts are considered, resulting in nanoparticles of FesO4 type (C. M. Cheng, et al. J. Magn. Magn. Mater. 2009, 321, 2663-2669; A. Mukhopadhyay, et al. ACS Appl. Mater. Interfaces 2012, 4, 142-149; J. Muro-Cruces, et al. ACS Nano 2019, 13, 7716- 7728).
• a method of preparing a biologically active dispersed system (nano-liquid) based on iron(II, III) oxide nanoparticles is known from the application description RU2493857 Cl .
• the method includes the preparation of a 3-6% solution of low molecular weight polyvinylpyrrolidone 8000 ⁇ 2000 (MW), in which the solvent is a liquid containing 2.75-5.5 g of sodium chloride, 0.21- 0.42 g of potassium chloride, 0.25-0.5 g of calcium chloride, 0.00025-0.005 g of magnesium chloride, 0.115-0.23 g of sodium bicarbonate and water.
• the resulting solution is added to a powder mixture of USPIO-grade iron(II, III) oxide nanoparticles with sizes of 5-8 nm, deposited on sodium chloride crystals. The whole mixture is stirred and kept at +60 °C for 2 hours. The resulting liquid is gradually cooled to room temperature (+20 °C) with subsequent separation from the precipitate.
• the reaction was further carried out in a high-temperature/high-pressure reactor for 6 hours at 200 °C, then the particles were cooled to room temperature. The resulting particles were collected in an external magnetic field. The particles were washed two or three times with water and ethanol, then heated to 500 °C (at 1 °C/min) and sintered for 3 hours. From patent description KR101280808 Bl, ferritic superparamagnetic nanoparticles exhibiting high magnetic induction heating capability and specific loss force in low magnetic field and frequency range, harmless to the human body, and a method of producing them are known.
• iron(III) acetylacetonate and a raw material solution at room temperature containing at least one material selected from the group consisting of Mg, Mn, Ni, Zn and Co is heated to 195 °C and then maintained at the same temperature, after which it was heated to 200-204 °C and then to 203-210 °C.
• Fe(III) acetylacetonate and a raw material solution at room temperature containing at least one material selected from the group consisting of Mg, Mn, Ni, Zn and Co is heated to 120-140 °C for 25 min, and then maintained at the same temperature for 55 to 65 min.
• heating of the solution, of the raw material obtained in the preliminary stage is carried out to 200 to 210 °C for 18 to 23 minutes, and then maintained at the same temperature for 55 to 62 minutes.
• the next stage is heating for 6 to 12 minutes to the boiling point of the solvent, and then maintaining the raw material solution at the same temperature for 45 to 55 minutes.
• the application description US20160176722 presents a method for producing magnetite and ferrite nanoparticles in a single vessel in situ synthesis involving the following steps: mixing iron(III) nitrate [Fe(NOs)3] with fatty acid to form a mixture; mixing a solvent with the mixture; heating the solvent mixture and maintaining the solvent mixture at a temperature between 300 °C and 320 °C; and precipitating magnetite and ferrite nanoparticles; wherein the nanoparticles have a relative standard deviation of diameter less than or equal to 10%.
• a method for producing magnetic iron oxide nanoparticles which includes the following steps of adding Fe 2+ and Fe 3+ salts at a molar ratio of Fe 2+ salt to Fe 3+ salt (1.2-1.4) : 2 in distilled water, to which polyethylene glycol is added.
• the reaction is then carried out for 5-10 minutes under ultrasonic conditions at 30-50 °C to obtain the reaction liquid, carry out magnetic separation of the obtained reaction liquid with a magnet, and then wash the reaction liquid 3-5 times with ethanol to obtain iron oxide nanoparticles.
• the disclosed method does not require a nitrogen atmosphere, high pressure or high temperature, and has the advantages of simplicity, the use of readily available raw materials and the possibility of large-scale industrial production.
• reaction should be carried out with a device that allows the reaction mixture to be subjected to barbotage with an Ar/C mixture (volume ratio of 1 : 4).
• This activity requires the use of a suitable specialized apparatus, also bearing in mind the required flow rate of these gases indicated by the authors (100 mL min -1 ).
• EP2377811 A2 discloses a method for producing processed superparamagnetic ferrite nanoparticles doped with magnesium with a particle size of 10 nm.
• the disclosed method includes mixing a raw material containing iron(III) acetylacetonate, magnesium and a solvent; performing a primary heat treatment to produce nanoparticle embryos; and performing a secondary heat treatment to produce nanoparticles, followed by washing, centrifugation, drying and grinding of the nanoparticles.
• the temperature of the mixture was gradually raised to 200 °C over 30 minutes and maintained at that level for another 30 minutes.
• the second heat treatment the temperature of the mixture was gradually raised to the melting point of benzyl ether, that is, 296 °C, over about 30 minutes.
• the purpose of the invention is to develop a new method for obtaining ultrafine superparamagnetic gamma iron(III) oxide (USPIO) doped with magnesium nanoparticles with improved magnetic properties.
• USPIO superparamagnetic gamma iron(III) oxide
• ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium with improved magnetic properties can be easily obtained using milder process conditions in air, commercially available reactants, and without the need to carry out the reaction in an atmosphere of argon or Ar/Oi.
• USPIO superparamagnetic gamma iron(III) oxide
• the object of the invention is a method for obtaining ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium with improved magnetic properties, characterized in that it includes the following steps: a) mixing iron(III) acetylacetonate, magnesium acetate tetrahydrate, dibenzyl ether and oleic acid at room temperature; b) bringing the mixture obtained by step a) to a temperature of 190-200 °C in 25-30 min; c) heating the mixture for 50 min at 190-200 °C; d) heating the mixture for 80 min at 230-235 °C; e) cooling the mixture to room temperature and washing it out; f) separation of nanoparticles with a magnet; g) stabilization of purified nanoparticles with a stabilizer that is mPEG-silane; whereby, stages (a-g) are conducted in an atmosphere that is air.
• Another object of the invention are ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium obtained by the method according to the invention characterized by the fact that their average size is 27-28 nm, the maximum magnetization based on hysteresis loop registration is 65 emu/g.
• USPIO superparamagnetic gamma iron(III) oxide
• the invention provides the following benefits:
• nanoparticles e.g., improved magnetic and hyperthermal properties in an alternating magnetic field
• Nanoparticles produced by the method according to the invention may find application in nanomedicine, particularly in oncology treatment using magnetic hyperthermia.
• the invention relates to a method of obtaining ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium characterized by improved magnetic and hyperthermal properties in an alternating magnetic field.
• USPIO superparamagnetic gamma iron(III) oxide
• the reaction is carried out in air. Iron(III) acetylacetonate and magnesium acetate tetrahydrate are placed in a flask. After adding dibenzyl ether and oleic acid, the mixture is stirred at room temperature for 15 minutes. In 30 minutes, the mixture is brought to 200 °C and heated at 200 °C for 50 minutes. Then, the temperature of the reaction mixture is quickly (i.e., within about 5 minutes) raised to 230 °C and the process is continued at this temperature for 80 minutes. After the mixture has cooled to room temperature, rinsing is carried out.
• the mixture is brought to 190 °C in 25 minutes and then heated at this temperature for 50 minutes.
• the temperature of the reaction mixture is quickly (i.e., within about 5 minutes) raised to 235 °C and the process is continued at this temperature for 80 minutes. After the mixture has cooled to room temperature, rinsing is carried out.
• the obtained precipitate is centrifuged. After removing the supernatant after the last wash, the obtained precipitate is poured over a mixture of ethanol, oleic acid and ammonia and shaken at room temperature for 2 hours. The precipitate is separated from the supernatant with a magnet and washed with acetone. Toluene is added to the resulting precipitate, shaken for 10 minutes and then triethylamine and mPEG-silane (methoxy-poly(ethylene glycol)-silane) are added. The mixture is stirred with a magnetic stirrer at 80 °C for 24 hours.
• the invention relates to ultrafme superparamagnetic magnesium-doped gamma iron(III) oxide (USPIO) nanoparticles, which were produced by the method according to the invention, whose average size is 27-28 nm, the maximum magnetization based on hysteresis loop registration is 65 emu/g.
• the ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles obtained by the method according to the invention doped with magnesium according to the invention have the following properties:
• Average particle size (based on TEM): 28 nm
• Average particle size (based on XRD): 27 nm
• Powder diffractogram (XRD): 20 220, 311, 400, 422, 511, 440 deg
• the elemental composition (based on EDS) is shown in Table 1:
• the ablative temperature (43.5 °C) is reached in the first minute of magnetization.
• Example 1 The invention is shown in the following non-limiting implementation examples.
• Example 1 The invention is shown in the following non-limiting implementation examples.
• the reaction is carried out in air. Iron(III) acetylacetonate (2.0 mmol) and magnesium acetate tetrahydrate (0.13 mmol) are placed in a flask. After adding dibenzyl ether (20 mL) and oleic acid (1.2 mmol), the mixture is stirred at room temperature for 15 minutes. In 30 minutes, the mixture is brought to 200 °C and heated at 200 °C for 50 minutes. Then, the temperature of the reaction mixture is quickly raised to 230 °C and the process continues at this temperature for 80 minutes. After the mixture has cooled to room temperature, ethanol (70 mL) is added. The resulting precipitate is centrifuged (5000 rpm, 25 min) and washed several times with ethanol.
• the resulting precipitate is poured over a mixture of ethanol (20 mL), oleic acid (6 mL) and ammonia (1.5 mL) and shaken (500 rpm) at room temperature for 2 hours.
• the precipitate is separated from the supernatant with a magnet and washed with acetone.
• Toluene (15 mL) is added to the resulting precipitate, shaken for 10 minutes and then triethylamine (8 mL) and mPEG-silane (550 Da; 1 mL) are added.
• the mixture is stirred with a magnetic stirrer at 80 °C for 24 hours.
• the precipitate is separated from the supernatant using a magnet, washed with toluene, ethanol and water to obtain ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium with improved magnetic properties.
• USPIO superparamagnetic gamma iron(III) oxide
• the reaction is carried out in air. Iron(III) acetylacetonate (2.0 mmol) and magnesium acetate tetrahydrate (0.13 mmol) are placed in a flask. After adding dibenzyl ether (20 mL) and oleic acid (1.2 mmol), the mixture is stirred at room temperature for 15 minutes. In 25 minutes, the mixture is brought to 190 °C and heated at 190 °C for 50 minutes. Then, the temperature of the reaction mixture is quickly raised to 235 °C and the process continues at this temperature for 80 minutes. After the mixture has cooled to room temperature, ethanol (70 mL) is added.
• the resulting precipitate is centrifuged (5000 rpm, 25 min) and washed several times with ethanol. After removing the supernatant after the last washing, the resulting precipitate is poured over a mixture of ethanol (20 mL), oleic acid (6 mL) and ammonia (1.5 mL) and shaken (500 rpm) at room temperature for 2 hours. The precipitate is separated from the supernatant with a magnet and washed with acetone. Toluene (15 mL) is added to the resulting precipitate, shaken for 10 minutes and then triethylamine (8 mL) and mPEG-silane (550 Da; 1 mL) are added.
• Ultrafine superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium were produced by the method according to example 1.
• superparamagnetic gamma iron(III) oxide (USPIO) nanoparticles doped with magnesium have the following properties:
• Average particle size (based on TEM): 28 nm
• Average particle size (based on XRD): 27 nm
• Powder diffractogram (XRD): 20 220, 311, 400, 422, 511, 440 deg
• the elemental composition (based on EDS) is shown in Table 1.
• the ablative temperature (43.5 °C) is reached in the first minute of magnetization.

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• 2022
  • 2022-04-11 PL PL440904A patent/PL247933B1/pl unknown
• 2023
  • 2023-04-11 WO PCT/PL2023/000021 patent/WO2023200345A1/en not_active Ceased

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