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1. WO2014081322 - SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES WITH ULTRA-THIN POLYMER LAYERS, THE METHOD OF THEIR PREPARATION AND APPLICATION

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Patent claims

1. Superparamagnetic iron oxide nanoparticles with ultra-thin polymer layers, wherein

nanoparticles consist of:

a. superparamagnetic iron oxides cores co-precipitated with a polycation, b. hydrophilic layer made of at least one ultrathin layer of a polyelectrolyte.

2. Superparamagnetic iron oxide nanoparticles according to claim 1, wherein first ultra-thin layer of polyelectrolyte is obtained as a result of co-precipitation of nanoparticles in the presence of polymer, and other odd layers, deposited on the surface of the obtained nanoparticles, consist of a polycation.

3. Superparamagnetic iron oxide nanoparticles according to claim 2, wherein polycation is selected from the group of natural or modified polysaccharides containing positively charged groups, such as: ammonium, pyridinium or phosphonium.

4. Superparamagnetic iron oxide nanoparticles according to claims 2 or 3, wherein the

polycation is chitosan modified with cationic ammonium groups.

5. Superparamagnetic iron oxide nanoparticles according to claim 1, wherein second ultra-thin layer of polyelectrolyte and more even layers consist of a polyanion.

6. Superparamagnetic iron oxide nanoparticles according to claim 5, wherein the polyanion is a polymer from the group consisting of natural or modified polysaccharides containing negatively charged functional groups, such as sulfonate, sulfate, carboxyl or phosphate.

7. Superparamagnetic iron oxide nanoparticles according to claims 5 or 6, wherein the

polyanion is a polymer constituting the anionic chitosan derivative or heparin.

8. Superparamagnetic iron oxide nanoparticles according to the claim 7, wherein the polymer forming an anionic chitosan derivative is carboxymethylchitosan modified with sulfur trioxide complex.

9. Superparamagnetic iron oxide nanoparticles according to the claim 1, wherein the

nanoparticles form a suspension in aqueous phase.

10. Superparamagnetic iron oxide nanoparticles according to claim 1, wherein the

nanoparticles are coated with such a number of coatings that their average size is 5-200 nm and/or the diameter of the iron oxide core is 5-20 nm and/or the thickness of the polymer coating is 0.1-100 nm.

11. Superparamagnetic iron oxide nanoparticles according to claim 1, wherein hydrophilic coating is functionalized by attaching a fluorescent probe and/or a gadolinium compound and/or antibodies and/or antibodies aptamers and/or polyelectrolyte layer having fluorinated groups to it.

12. Superparamagnetic iron oxide nanoparticles according to claim 11, wherein the fluorescent probe is selected from the group consisting of: fluorescamine, fluorescein, cyanine, rhodamines or functionalized quantum dots.

13. Superparamagnetic iron oxide nanoparticles according to claim 11, wherein the gadolinium compound is selected from the group consisting of chelates of gadolinium ions with diethylenetriaminepentaacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).

14. Superparamagnetic iron oxide nanoparticles according to claim 11, wherein the antibody is selected from the group consisting of monoclonal antibodies against cell adhesion molecules, including, in particular, VCAM-1, monoclonal antibodies against

P-selectin or monoclonal antibodies against E-selectin.

15. Superparamagnetic iron oxide nanoparticles according to claim 11, wherein the antibody aptamers are selected from the group consisting of monoclonal antibody aptamers against cell adhesion molecules, against P-selectin or E-selectin.

16. Superparamagnetic iron oxide nanoparticles according to claim 11, wherein the

polyelectrolyte layers having fluorinated groups are poly(N,N-dimethyl-N-4'-vinylbenzyl- N-2-(perfuorooctanoyl-N'-methylimino)ethylammonium chloride)-co-(N,N,N-trimethyl-N- 4'-vinylbenzylammonium chloride) .

17. The method of preparation of superparamagnetic nanoparticles according to claims from 1 to 16, wherein an aqueous solution of the cationic polysaccharide at a concentration of 0.1-10 g/dm3 is added to salts of iron(II) and iron(III) to iron ions concentration 0.001-0.500 mol/dm3, and then purged with an inert gas and stirred at 10 -60 °C, then mixed with the base to reach pH of the mixture higher than 8, in which the precipitation of

superparamagnetic iron oxide nanoparticles having durable positive charge occurs while purging with an inert gas and stirring, and after purification, the surface of the

superparamagnetic iron oxide nanoparticles with positive surface charge can be covered with at least one layer of the counter-charged polyelectrolyte and/or subsequently functionalized.

18. The method according to claim 17, wherein an aqueous solution of cationic polysaccharide is ammonium chitosan derivative.

19. The method according to claim 17, wherein the concentration of polysaccharide is 0.5-5 g/dm3.

20. The method according to claim 17, wherein as iron(II) and iron(III) salts, iron(II) and iron(III) chlorides are used.

21. The method according to claim 17 and 20, wherein iron(II) and iron(III) salts are used in a molar ratio of 1 :2.

22. The method according to claim 17, wherein the concentration of iron ions is 0.002-0.200 mol/dm3.

23. The method according to claim 17, wherein as a base, ammonia is used.

24. The method according to claim 17, wherein cationic polysaccharide solution containing iron ions is mixed with the base to reach the mixture pH higher than 9.

25. The use of superparamagnetic nanoparticles according to claims from 1 to 16 or made by the process according to claims from 17 to 24, as a contrast agent in magnetic resonance imaging and/or fluorescence imaging and/or fluorescence microscopy.