Delivery of Nanoparticles and/or Agents to Cells

• US 20080213377A1
• Filed: 12/07/2007
• Published: 09/04/2008
• Est. Priority Date: 12/08/2006
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Bhatia, Sangeeta N., Agrawal, Amit, Derfus, Austin M., von Maltzahn, Geoffrey, Harris, Todd, Min, Dal-Hee
• Application Number:
  US11/952,614
• Publication Number:
  US 20080213377A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 49/0067 quantum dots, fluorescent nanocrystals
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention provides systems, methods, and compositions for targeted delivery of nanoparticles and/or agents to tissues, cells, and/or subcellular locales. In general, compositions comprise a nanoparticle (e.g. quantum dot, polymeric particle, etc.), at least one modulating entity (such as a targeting moiety, transfection reagent, protective entity, etc.), and at least one agent to be delivered (e.g. therapeutic, prophylactic, and/or diagnostic agent). The present invention provides methods of making and using nanoparticle entities in accordance with the present invention.

Claims

1. A conjugate comprising:

a nanoparticle;

at least one modulating entity; and

at least one agent to be delivered.

2. The conjugate of claim 1, wherein the nanoparticle comprises a polymeric matrix.

6. The conjugate of claim 1, wherein the nanoparticle is a non-polymeric particle.

10. The conjugate of claim 1, wherein the modulating entity is a targeting entity.

11. The conjugate of claim 10, wherein the targeting entity is selected from the group consisting of peptides, nucleic acids, small molecules, carbohydrates, and lipids.

21. The conjugate of claim 1, wherein the modulating entity is polyethylene glycol (PEG).

23. The conjugate of claim 1, wherein the agent to be delivered is a nucleic acid.

28. The conjugate of claim 1, wherein the agent to be delivered is a protein.

31. The conjugate of claim 1, wherein the agent to be delivered is a small molecule.

36. The conjugate of claim 1, wherein the agent to be delivered is useful for treating liver diseases.

47. The conjugate of claim 1, wherein the nanoparticle is covalently associated with the modulating entity.

49. The conjugate of claim 47, wherein the covalent association is mediated by a linker.

51. The conjugate of claim 49, wherein the linker is a protease-cleavable linker.

52. The conjugate of claim 51, wherein the protease-cleavable linker is cleaved by a protease, wherein the protease is preferentially expressed in tumor cells relative to non-tumor cells.

73. A method comprising steps of:

providing a subject suffering from, susceptible to, or displaying one or more symptoms of a disease, disorder, or condition; and

administering the conjugate of claim 1 to the subject such that the disease, disorder, or condition is treated.

74. The method of claim 73, wherein the disease, disorder, or condition is cancer.

75. The method of claim 73, wherein the disease, disorder, or condition is a liver disease.

3-5. -5. (canceled)

7-9. -9. (canceled)

12-20. -20. (canceled)

22. (canceled)

24-27. -27. (canceled)

29-30. -30. (canceled)

32-35. -35. (canceled)

37-46. -46. (canceled)

48. (canceled)

50. (canceled)

53-66. -66. (canceled)

67. A conjugate comprising:

a nanoparticle;

a modulating entity;

polyethylene glycol (PEG); and

an agent to be delivered.

68-72. -72. (canceled)

76-86. -86. (canceled)

87. A method comprising steps of:

providing;

a nanoparticle;

at least one modulating entity; and

at least one agent to be delivered; and

contacting the nanoparticle, at least one modulating entity, and at least one agent to be delivered such that the nanoparticle, at least one modulating entity, and at least one agent become physically associated with one another.

88. A method comprising steps of:

providing;

a nanoparticle;

at least one modulating entity; and

at least one agent to be delivered; and

contacting the nanoparticle and the at least one modulating entity to allow formation of a complex comprising the nanoparticle and the modulating entity; and

contacting the complex with the agent to be delivered.