Aptamer-Directed Drug Delivery

• US 20110052697A1
• Filed: 05/17/2007
• Published: 03/03/2011
• Est. Priority Date: 05/17/2006
• Status: Abandoned Application

• Current Assignee: Brigham and Women's Hospital Incorporated, Gwangju Institute of Science and Technology, Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated, Gwangju Institute of Science and Technology, Massachusetts Institute of Technology
• Inventors: Zhang, Liangfang, Teply, Benjamin, Bagalkot, Vaishali, Levy-Nissenbaum, Etgar, Jon, Sangyong, Farokhzad, Omid C., Langer, Robert S.
• Application Number:
  US12/301,225
• Publication Number:
  US 20110052697A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 49/0019 characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0067 quantum dots, fluorescent nanocrystals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 a therapeutic agent organs, tissues, cells, extracellular matrix components, and intracellular compartments. The present invention provides a complex comprising a therapeutic or diagnostic agent and a nucleic acid targeting moiety, wherein the agent non-covalently associates with base pairs of the nucleic acid targeting moiety. The invention provides targeted particles comprising a particle and an inventive complex. The present invention provides methods of designing, manufacturing, and using inventive complexes and targeted particles.

Claims

1. A complex, comprising:

a nucleic acid targeting moiety; and

a therapeutic agent, wherein the therapeutic agent is capable of associating with the base pairs of the nucleic acid targeting moiety.

2. The complex of claim 1, wherein the therapeutic agent is non-covalently associated with the nucleic acid targeting moiety.

3. The complex of claim 1, wherein the nucleic acid targeting moiety is an aptamer.

18. The complex of claim 2, wherein the specific binding of the nucleic acid targeting moiety to a target results in delivery of the therapeutic agent to target cells, and wherein the target comprises a protein.

19. The complex of claim 1, wherein the target is selected from the group consisting of cell surface receptors, integrins, transmembrane proteins, ion channels, membrane transport proteins, intracellular proteins, soluble proteins, small molecules, tumor markers, characteristic portions thereof, and combinations thereof.

21. The complex of claim 2, wherein the specific binding of the nucleic acid targeting moiety to a target results in delivery of the therapeutic agent to target cells, and wherein the target is a prostate cancer specific marker.

23. The complex of claim 21, wherein the target is PMSA.

28. The complex of claim 2, wherein the specific binding of the nucleic acid targeting moiety to a target results in delivery of the therapeutic agent to target cells, and wherein the specific binding of the nucleic acid targeting moiety to the target depends on the three dimensional characteristics of the targeting moiety.

29. The complex of claim 1, wherein the therapeutic agent intercalates between the base pairs of the nucleic acid targeting moiety.

30. The complex of claim 1, wherein the therapeutic agent is an anthracycline.

4-17. -17. (canceled)

20. (canceled)

22. (canceled)

24-27. -27. (canceled)

31-44. -44. (canceled)

45. A targeted particle, comprising:

a particle; and

a complex;

wherein the complex comprises;

a nucleic acid targeting moiety; and

a therapeutic agent, wherein the therapeutic agent is capable of intercalating between the base pairs of the nucleic acid targeting moiety.

46. The targeted particle of claim 45, wherein the particle comprises a polymeric matrix, and wherein the polymeric matrix comprises a polyester.

51. The targeted particle of claim 46, wherein the polyester is selected from the group consisting of PLGA, PLA, PGA, polycaprolactone, and polyanhydrides.

53. The targeted particle of claim 45, wherein the polymeric matrix comprises two or more polymers.

57. The targeted particle of claim 53, wherein at least one polymer is polyethylene glycol (PEG).

58. The targeted particle of claim 45, wherein the polymeric matrix comprises a copolymer of two or more polymers.

113. The targeted particle of claim 45, wherein the complex is non-covalently associated with the particle.

47-50. -50. (canceled)

52. (canceled)

54-56. -56. (canceled)

59-112. -112. (canceled)

114-143. -143. (canceled)

144. A method of preparing a targeted particle comprising:

providing a nucleic acid targeting moiety;

providing a therapeutic agent, wherein the therapeutic agent is capable of intercalating between the base pairs of the nucleic acid targeting moiety;

mixing the nucleic acid targeting moiety with the therapeutic agent to prepare a complex;

providing a polymer, wherein the polymer comprises a polyester;

producing a particle comprising a polymeric matrix; and

associating the particles with the complex;

wherein the polymer comprises a polyester, and wherein the nucleic acid targeting moiety targets prostate cancer cells.

145. The method of claim 144, further comprising a step of purifying the particles.

146. The method of claim 144, further comprising a step of isolating particles of a predetermined size.

147-148. -148. (canceled)