Internalization of proteins into hollowed gold nanostructures

Patent metadata

Field	Value
Publication number	US-9562225-B2
Application number	US-201514676258-A
Country	US
Kind code	B2
Filing date	Apr 1, 2015
Priority date	Oct 7, 2014
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

Provided is a gold nanocage with pores, charged ligand molecules covalently bound to internal surfaces of the gold nanocage, and payload molecules electrostatically adsorbed onto said charged ligand molecules, wherein a pore diameter is between 1.2 and 20 times a gyration radius of the payload molecule. Also provided is a method for making a nanoparticle, including using polyvinylpyrrolidone as a capping agent in a galvanic replacement reaction to convert a silver nanocube into a gold nanocage having pores, replacing the polyvinylpyrrolidone on internal surfaces with charged ligand molecules, and electrostatically adsorbing payload molecules onto the charged ligand molecules, with a pore diameter less than twenty times a gyration radius of the payload molecule. Also provided is a method of delivering a pharmacological agent to a mammalian cell, including contacting the cell with a gold nanocage having pores, ligand molecules bound to internal surfaces, and pharmacological agent adsorbed onto ligand molecules.

First claim

The invention claimed is:

1. A nanoparticle comprising:
a gold nanocage comprising pores;
charged ligand molecules covalently bound to one or more surfaces of the gold nanocage, wherein at least some charged ligand molecules are covalently bound to internal surfaces of the gold nanocage; and
payload molecules electrostatically adsorbed onto said charged ligand molecules covalently bound to internal surfaces of the gold nanocage, wherein a diameter of one or more pores in the gold nanocage is between 1.2 and 20 times a gyration radius of the payload molecule.

2. The nanoparticle of claim 1 , wherein charged ligand molecules are covalently bound to an external surface of the gold nanocage and payload molecules are electrostatically adsorbed onto said charged ligand molecules covalently bound to external surfaces of the gold nanocage.

3. The nanoparticle of claim 1 , wherein the charged ligand molecules are negatively charged at physiological pH.

4. The nanoparticle of claim 1 , wherein charged ligand molecules are positively charged at physiological pH.

5. The nanoparticle of claim 1 , wherein payload molecules comprise nucleic acids, polypeptides, enzymes, antibodies, phospholipids, or any combination of the foregoing.

6. The nanoparticle of claim 1 , wherein payload molecules are not electrostatically adsorbed onto charged ligand molecules covalently bound to external surfaces of the gold nanocage.

7. The nanoparticle of claim 1 , wherein a radius of pores in the gold nanocage is between 1.2 and 5 times a gyration radius of the payload molecule and a length of the pores is between 1 nm and 20 nm.

8. The nanoparticle of claim 3 , wherein payload molecules comprise nucleic acids, polypeptides, enzymes, antibodies, phospholipids, or any combination of the foregoing.

9. The nanoparticle of claim 4 , wherein payload molecules comprise nucleic acids, polypeptides, enzymes, antibodies, phospholipids, or any combination of the foregoing.

10. A nanoparticle comprising:
a gold nanocage comprising pores;
charged ligand molecules covalently bound to one or more surfaces of the gold nanocage, wherein at least some charged ligand molecules are covalently bound to internal surfaces of the gold nanocage; and
payload molecules electrostatically adsorbed onto said charged ligand molecules covalently bound to internal surfaces of the gold nanocage, wherein a diameter of one or more pores in the gold nanocage is between 1.2 and 20 times a gyration radius of the payload molecule;
wherein the charged ligand molecules comprise ligands having a negative charge at physiological pH and the ligands having a negative charge at physiological pH are selected from the group consisting of mercaptohexanoic acid, para-mercaptobenzoic acid, mercaptohexadecanoic acid, and 11-mercaptoundecanoic acid.

11. The nanoparticle of claim 10 , wherein the ligands having a negative charge at physiological pH are 11-mercaptoundecanoic acid.

12. The nanoparticle of claim 10 , wherein charged ligand molecules are covalently bound to an external surface of the gold nanocage and payload molecules are electrostatically adsorbed onto said charged ligand molecules covalently bound to external surfaces of the gold nanocage.

13. The nanoparticle of claim 10 , wherein payload molecules comprise nucleic acids, polypeptides, enzymes, antibodies, phospholipids, or any combination of the foregoing.

14. The nanoparticle of claim 11 , wherein payload molecules comprise nucleic acids, polypeptides, enzymes, antibodies, phospholipids, or any combination of the foregoing.

15. The nanoparticle of claim 10 , wherein payload molecules are not electrostatically adsorbed onto charged ligand molecules covalently bound to external surfaces of the gold nanocage.

16. The nanoparticle of claim 10 , wherein a radius of pores in the gold nanocage is between 1.2 and 5 times a gyration radius of the payload molecule and a length of the pores is between 1 nm and 20 nm.

17. A nanoparticle comprising:
a gold nanocage comprising pores;
charged ligand molecules covalently bound to one or more surfaces of the gold nanocage, wherein at least some charged ligand molecules are covalently bound to internal surfaces of the gold nanocage; and
payload molecules electrostatically adsorbed onto said charged ligand molecules covalently bound to internal surfaces of the gold nanocage, wherein a diameter of one or more pores in the gold nanocage is between 1.2 and 20 times a gyration radius of the payload molecule;
wherein the charged ligand molecules comprise ligands having a positive charge at physiological pH and the ligands having a positive charge at physiological pH are selected from the group consisting of aminoethanethiol, N,N,N-trimethyl(11-mercaptoundecyl)ammonium chloride, and cysteamine.

18. The nanoparticle of claim 17 , wherein charged ligand molecules are covalently bound to an external surface of the gold nanocage and payload molecules are electrostatically adsorbed onto said charged ligand molecules covalently bound to external surfaces of the gold nanocage.

19. The nanoparticle of claim 17 , wherein payload molecules comprise nucleic acids, polypeptides, enzymes, antibodies, phospholipids, or any combination of the foregoing.

20. The nanoparticle of claim 17 , wherein payload molecules are not electrostatically adsorbed onto charged ligand molecules covalently bound to external surfaces of the gold nanocage.

21. The nanoparticle of claim 17 , wherein a radius of pores in the gold nanocage is between 1.2 and 5 times a gyration radius of the payload molecule and a length of the pores is between 1 nm and 20 nm.

Assignees

• Qian Xi
• Gagner Jennifer E
• Dordick Jonathan S
• Siegel Richard W
• Rensselaer Polytech Inst

Inventors

• Qian Xi
• Gagner Jennifer E
• Dordick Jonathan S
• Siegel Richard W

Classifications

• C12Y302/01017

  Lysozyme (3.2.1.17) · CPC title

• C12Y304/21001

  Chymotrypsin (3.4.21.1) · CPC title

• C23C18/1657

  Electroless forming, i.e. substrate removed or destroyed at the end of the process · CPC title

• C12N9/2462

  Lysozyme (3.2.1.17) · CPC title

• C23C18/1635

  Composition of the substrate · CPC title