Hydrophobic nanotubes and nanoparticles as transporters for the delivery of drugs into cells

• US 8,246,995 B2
• Filed: 05/09/2006
• Issued: 08/21/2012
• Est. Priority Date: 05/10/2005
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Dai, Hongjie, Wender, Paul A., Liu, Zhuang, Wong Shi Kam, Nadine
• Primary Examiner(s): WOODWARD, CHERIE MICHELLE
• Application Number:
  US11/431,346
• Publication Number:
  US 20060275371A1
• Time in Patent Office: 2,296 Days
• Field of Search: None
• US Class Current: 424/489
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

Methods and materials for delivering biologically active molecules to cells in vitro or in vivo are provided. The methods and materials use carbon nanotubes or other hydrophobic particles, tubes and wires, functionalized with a linking group that is covalently bound to the nanotubes, or, alternatively, to the biologically active molecule, such as a protein. The biologically active molecule is preferably released from the nanotube when the complex has been taken up in an endosome.

Claims

1. A stable aqueous suspension of nanotube complexes suitable for delivery of a nanotube complex in said suspension to a living cell, said complex comprising:

(a) an individual carbon nanotube; and

(b) a biologically active molecule, wherein said biologically active molecule comprises a polynucleic acid or a polypeptide bound to a linking agent which is noncovalently bound to the carbon nanotube, whereby the complex may be disassociated to release the biologically active molecule in active form inside a cell; and

further comprising

(c) said linking agent comprising (i) a hydrophilic polymer and (ii) a hydrophobic polymer linked to the hydrophilic polymer, said hydrophilic polymer being covalently bound to the biologically active molecule.

2. The complex of claim 1 wherein said polypeptide is selected from the group consisting of enzymes, antibodies, peptides, and transcription factors.

3. The complex of claim 1 wherein said polynucleic acid is selected from the group consisting of RNA, siRNA, synthetic DNA, and cDNA.

4. The complex of claim 1 wherein said nanotubes are each between about 1 and 500 nm long and 1-5 nm in diameter.

5. The complex of claim 1 wherein the protein polypeptide has a molecular weight between 1 kD and 150 kD.

6. The complex of claim 1 wherein the nanotubes are single walled nanotubes.

7. The complex of claim 1 wherein the linking agent comprises a hydrophobic polymer comprising an aliphatic compound.

8. The complex of claim 3 wherein said siRNA silences an oncogene.

9. The complex of claim 3 wherein said siRNA silences a receptor.

10. The suspension of claim 1 wherein said linking agent comprises a cleavable linkage between said hydrophilic polymer and said biologically active molecule.

11. The suspension of claim 10 wherein said cleavable linkage comprises a disulfide linkage.

12. The suspension of claim 1 wherein said hydrophilc polymer is polyethylene glycol.

13. The suspension of claim 1 wherein said hydrophobic polymer is comprised in a phospholipid.

14. The suspension of claim 1 wherein said linking agent comprises polyethlene glycol-phospholipid.

15. The suspension of claim 14 wherein said phospholipid is terminated with an amine group for linkage to the hydrophilic polymer.