Mesoporous silica nanoparticles for biomedical applications

Patent metadata

Field	Value
Publication number	US-10668024-B2
Application number	US-201815996377-A
Country	US
Kind code	B2
Filing date	Jun 1, 2018
Priority date	Dec 6, 2007
Publication date	Jun 2, 2020
Grant date	Jun 2, 2020

Abstract

A submicron structure includes a silica body defining a plurality of pores that are suitable to receive molecules therein, the silica body further defining an outer surface between pore openings of said plurality of pores; and a plurality of anionic molecules attached to the outer surface of the silica body. The anionic molecules provide hydrophilicity to the submicron structure and are suitable to provide repulsion between other similar submicron structures, and the submicron structure has a maximum dimension less than one micron.

First claim

We claim:

1. A submicron structure for delivering drugs into cells, said structure comprising:
a silica body comprising a plurality of pores, wherein said pores are suitable to receive RNA, DNA, or a small molecule therein and to subsequently release said RNA, DNA, or small molecule therefrom, said silica body further defining an outer surface between pore openings of said plurality of pores; and
a plurality of anionic molecules attached only to said outer surface of said silica body such that said plurality of pores are free of said plurality of anionic molecules thereby permitting said plurality of pores to receive said RNA, DNA, or small molecule therein and to subsequently release said DNA, RNA, or small molecule therefrom; and
where said anionic molecules provide hydrophilicity to said submicron structure and are suitable to provide repulsion between other similar submicron structures.

2. The submicron structure of claim 1 , wherein said RNA, DNA, or small molecule comprises a small molecule.

3. The submicron structure of claim 1 , wherein said RNA, DNA, or small molecule comprises RNA or DNA.

4. The submicron structure of claim 2 , wherein said small molecule comprises a hydrophobic anti-cancer drug.

5. The submicron structure of claim 4 , wherein said hydrophobic anti-cancer drug comprises a drug selected from the group consisting of camptothecin, paclitaxel, resveratrol, etoposide, carmustine, and combinations thereof.

6. The submicron structure of claim 1 , wherein said plurality of anionic molecules comprise a phosphonate moiety.

7. The submicron structure of claim 6 , wherein said plurality of anionic molecules comprise a trihydroxysilylpropyl methylphosphonate.

8. The submicron structure of claim 1 , wherein said plurality of anionic molecules provide a negative zeta potential to said submicron structure.

9. The submicron structure of claim 1 , wherein said submicron structure, when administered to a subject forms a protein corona on the surface of said structure.

10. The submicron structure of claim 1 , wherein said submicron structure comprises a plurality of targeting molecules attached to the outer surface of said silica body, where said targeting molecules bind to a cancer cell.

11. The submicron structure of claim 10 , wherein said targeting molecules comprise folate ligands.

12. The submicron structure of claim 1 , wherein said submicron structure comprises a material that is optically dense to x-rays.

13. The submicron structure of claim 12 , wherein said material that is optically dense to x-rays comprises a gold nanoparticle.

14. The submicron structure of claim 1 , wherein said submicron structure comprises a nanoparticle of magnetic material formed within said silica body of said submicron structure.

15. The submicron structure of claim 14 , wherein said nanoparticle of magnetic material comprises an iron oxide.

16. The submicron structure of claim 14 , wherein said nanoparticle of magnetic material has a maximum dimension greater than about 5 nm and less than about 30 nm.

17. The submicron structure of claim 1 , wherein said submicron structure comprises a fluorescent molecule attached to said silica body of said submicron structure.

18. The submicron structure of claim 17 , wherein said fluorescent molecule comprise an amine-reactive fluorescent dye attached by being conjugated with an amine-functionalized silane.

19. The submicron structure of claim 17 , wherein said fluorescent molecule is selected from the group consisting of fluorescein isothiocyanate, N-hydroxysuccinimide fluorescein (NHS-fluorescein), rhodamine B isothiocyanate, tetramethylrhodamine B isothiocyanate, and Cy5.5 NHS ester.

20. The submicron structure of claim 1 , wherein the average diameter of the submicron structure is at least 50 nm and less than 150 nm.

21. A method of delivering RNA, DNA, or small molecule to a cancer cell, said method comprising contacting said cancer cell with a submicron structure of claim 1 , wherein the pores of said submicron structure contain said RNA, DNA, or small molecule.

Assignees

• Univ California

Inventors

• Liong Monty
• Lu Jie
• Tamanoi Fuyuhiko
• Zink Jeffrey I
• Nel Andre E

Classifications

• A61K49/0093

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K49/0043

  Fluorescein, used in vivo · CPC title

• A61K9/5115 Primary

  Inorganic compounds · CPC title