REMOTELY TRIGGERED RELEASE FROM HEATABLE SURFACES

• US 20090093551A1
• Filed: 12/07/2007
• Published: 04/09/2009
• Est. Priority Date: 12/08/2006
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Derfus, Austin M., von Maltzahn, Geoffrey, Bhatia, Sangeeta N.
• Application Number:
  US11/952,993
• Publication Number:
  US 20090093551A1
• Time in Patent Office: Days
• US Class Current: 514/773
• 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 particle conjugates for drug delivery. Such conjugates comprise one or more heatable surfaces, one or more thermally-responsive linkers, and one or more agents to be delivered. In some embodiments, conjugates and populations of conjugates can be used to treat and/or diagnose a disease, disorder, and/or condition. The present invention provides methods for producing and/or using thermally-responsive conjugates.

Claims

1. A conjugate, comprising:

(i) a heatable surface, wherein the heatable surface heats in response to an external stimulus,

(ii) at least one agent to be delivered; and

(iii) at least one thermally-responsive linker, wherein a first end of the thermally-responsive linker is associated with the heatable surface, wherein a second end of the thermally-responsive linker is associated with the agent to be delivered, and wherein the thermally-responsive linker is disrupted at a trigger temperature;

wherein the agent to be delivered is released from the conjugate when the thermally-responsive linker is heated to the trigger temperature or to temperatures higher than the trigger temperature.

5. The conjugate of claim 1, wherein the heatable surface comprises a nanoparticle.

7. The conjugate of claim 1, wherein the external stimulus is an electromagnetic (EM) field.

9. The conjugate of claim 1, wherein the thermally-responsive linker is selected from the group consisting of nucleic acids, peptides, proteins, lipids, carbohydrates, and polymers.

58. The conjugate of claim 1, wherein the agent to be delivered is a therapeutic agent, diagnostic agent, prophylactic agent, or nutraceutical agent.

80. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable excipient.

81. A plurality of the conjugates of claim 1, wherein all of the conjugates of the plurality of conjugates are identical to one another.

82. A plurality of the conjugates of claim 1, wherein the plurality of conjugates comprises one or more populations of non-identical conjugates.

90. A pharmaceutical composition comprising the plurality of conjugates of claim 81 or 82 and a pharmaceutically acceptable excipient.

91. A method of treating a disease, condition, or disorder comprising administering the conjugate of claim 1 to a subject.

92. A method of treating a disease, condition, or disorder comprising administering the plurality of conjugates of claim 81 to a subject.

93. A method of treating a disease, condition, or disorder comprising administering the plurality of conjugates of claim 82 to a subject.

95. A method, comprising steps of:

providing a subject; and

administering the pharmaceutical composition of claim 80 or 90 to a subject.

2-4. -4. (canceled)

6. (canceled)

8. (canceled)

10. (canceled)

11. The conjugate of claim 10, wherein the thermally-responsive linker is a nucleic acid, wherein the nucleic acid comprises a duplex region, and wherein the duplex region comprises two nucleic acid strands that are associated with one another via Watson-Crick base pairing.

14. The conjugate of claim 10, wherein the thermally-responsive linker is a single-stranded nucleic acid.

12-13. -13. (canceled)

15-57. -57. (canceled)

59-79. -79. (canceled)

83-89. -89. (canceled)

94. (canceled)

96-99. -99. (canceled)

100. A method, comprising:

providing at least one heatable surface, at least one thermally-responsive linker, and at least one therapeutic agent to be delivered; and

allowing the at least one heatable surface, at least one thermally-responsive linker, and at least one therapeutic agent to be delivered to self-assemble such that thermally-responsive conjugates are formed.

101. A method, comprising:

providing at least one heatable surface, at least one thermally-responsive linker, and at least one therapeutic agent to be delivered; and

covalently associating the at least one heatable surface, at least one thermally-responsive linker, and at least one therapeutic agent to be delivered to one another such that thermally-responsive conjugates are formed.

102. (canceled)

103. In a method of delivering an agent, the improvement that comprises:

delivering the agent in the context of a conjugate of the agent and a heatable surface that heats in response to an external stimulus,

wherein the agent and core are associated with one another in the conjugate by means of a thermally-responsive linker that breaks at or above a trigger temperature such that, when the conjugate is exposed to the stimulus, the core heats to a temperature at or above the trigger temperature and the linker breaks so that the agent is released.