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1. WO2017195127 - PROCESS FOR THE PREPARATION OF HOLLOW NANOPARTICLES WITH A METAL CORE

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[ EN ]

CLAIMS

1. A process for the preparation of silica hollow nanoparticles, having a diameter smaller than 100 nm and a metal core inside a cavity comprising inorganic nanostructures, each having a diameter smaller than 3 nm and forming together an aggregate with poly(4-vinylpyridine), said process comprising the following steps:

i) formation of ultra-small hydrophilic inorganic nanostructures, provided with a negatively charged coating, by reduction with sodium borohydride of an acid or a salt of a metal in alcoholic solution;

ii) formation of an aggregate with poly(4-vinylpyridine) as an aggregating agent of said hydrophilic inorganic nanostructure, by addition of said poly(4-vinylpyridine) to an alcoholic solution of the inorganic nanostructures obtained from step i);

iii) formation of said silica hollow nanoparticles having in the cavity a metal core comprising said aggregate of hydrophilic inorganic nanostructures by hydrolysis of tetraethyl orthosilicate catalysed by ammonia in a mixture of ethanol and water in the presence of said aggregate as obtained from step ii).

2. The process according to claim 1 , wherein said inorganic nanostructures are selected from among nanoparticles of superparamagnetic iron oxide, clusters of a metal selected from gold, silver and platinum, and mixtures of said clusters.

3. The process according to claim 2, wherein said metal is gold.

4. The process according to claim 1 , wherein said silica hollow nanoparticles have a diameter comprised between 30 and 40 nm, and said inorganic nanostructures have a diameter comprised between 1 and 2 nm.

5. The process according to any one of the preceding claims, wherein said coating of the inorganic nanostructures is formed by a coating agent provided with carboxylic acid groups.

6. The process according to claim 5, wherein said coating agent is glutathione.

7. The process according to any one of the preceding claims, wherein said inorganic nanostructures coming from step i) are subject to functionalization of the coating with one or more functional molecules having pharmacological activity before being aggregated in the subsequent step ii).

8. The process according to any one of the preceding claims, further comprising a

procedure of modification and/or functionalization of the outer surface of said silica nanoparticles with one or more molecules, for instance antibodies, aptamers, fluorophores, proteins, polymers or silanising peptides.

9. The process according to any one of the preceding claims, further comprising a procedure of lyophilisation of the silica nanoparticles obtained from step iii).

10. An intermediate in the process for the preparation of nanoparticles as defined in claims 1 to 9, consisting of an aggregate of inorganic nanostructures with a negatively charged coating, each having a diameter smaller than 3 nm and forming together an aggregate with poly(4-vinylpyridine).

1 1. Use of the intermediate as defined in claim 8, for the preparation of silica hollow nanoparticles with a metal core inside their cavity comprising inorganic nanostructures in the form of an aggregate.

12. Hollow silica nanoparticles obtainable by the process of preparation of nanoparticles as defined in claims 1 to 9, having a diameter smaller than 100 nm and a metal core inside their cavity comprising inorganic nanostructures with a negatively charged coating, each having a diameter smaller than 3 nm and forming together an aggregate with poly(4-vinylpyridine).

13. The nanoparticles according to claim 12, having a diameter ranging between 30 and 40 nm and comprising in the core inside their cavity inorganic nanostructures each of dimensions ranging between 1 and 2 nm.

14. The intermediate of claim 10 or the nanoparticles of claim 12, wherein said inorganic nanostructures are clusters of gold.

15. Use of the nanoparticles as defined in claims 12-14, as diagnostic and/or therapeutic agents suitable for administration by enteral or parenteral route into the human body for bioimaging techniques and/or for radio-therapy or chemo-therapy techniques.