Triggered Self-Assembly of Nanoparticles In Vivo

• US 20090246142A1
• Filed: 03/09/2007
• Published: 10/01/2009
• Est. Priority Date: 03/10/2006
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Harris, Todd J., Bhatia, Sangeeta N., von Maltzahn, Geoffrey
• Application Number:
  US12/282,462
• Publication Number:
  US 20090246142A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 49/1833 having a (super)(para)magnetic core coated or functionalised with a small organic molecule oligomeric, polymeric, dendrimeric A61K49/1851
• CPC Class Codes: A61K 49/186 the organic macromolecular compound being polyethyleneglycol [PEG]
• CPC Class Codes: A61K 49/1866 the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid
• CPC Class Codes: A61K 49/1887 Agglomerates, clusters, i.e. more than one (super)(para)magnetic microparticle or nanoparticle are aggregated or entrapped in the same maxtrix
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention provides triggered self-assembly nanosystems. Such nanosystems comprise a population of triggered self-assembly conjugates, each conjugate comprising one or more monomeric units and one or more complementary binding moieties. In some embodiments, inventive nanosystems and conjugates can be used to treat and/or diagnose a disease, disorder, and/or condition.

Claims

1-36. -36. (canceled)

37. A self-assembly nanosystem, comprising:

a plurality of conjugates, wherein each conjugate comprises;

a biologically compatible monomeric unit,

at least one complementary binding moiety conjugated to the biologically compatible monomeric unit; and

at least one removably associated blocking agent, wherein the blocking agent shields the complementary binding moiety until the blocking agent is removed, and

wherein the monomeric unit, complementary binding moiety, and removably associated blocking agent are selected and arranged such that the conjugate adopts at least two relative configurations, a first relative configuration in which individual conjugates have not undergone self-assembly, and a second relative configuration in which individual conjugates have self-assembled to form an aggregate, wherein conversion from the first to the second relative configuration occurs in response to a trigger.

38. The self-assembly nanosystem of claim 37, wherein the biologically compatible monomeric unit is selected from the group consisting of a dendrimer, a nanoemulsion, a liposome, a polymer, a micelle, a protein, and a peptide.

39. The self-assembly nanosystem of claim 37, wherein the biologically compatible monomeric unit comprises a nanoparticle.

40. The self-assembly nanosystem of claim 37, wherein the biologically compatible monomeric unit comprises a microparticle.

41. The self-assembly nanosystem of claim 37, wherein the complementary binding moiety is selected from the group consisting of a ligand, an anti-ligand, a receptor, an antibody, an antigen, a phage-display derived peptide, a nucleic acid, an aptamer, a charge complex, and a reactive chemical moiety, and combinations thereof.

42. The self-assembly nanosystem of claim 37, wherein the complementary binding moiety is streptavidin.

43. The self-assembly nanosystem of claim 37, wherein the complementary binding moiety is biotin.

44. The self-assembly nanosystem of claim 37, wherein the removably associated blocking agent is selected from the group consisting of polaxamines;

poloxamers;

polyethylene glycol (PEG);

peptides or other synthetic polymers of sufficient length and density to both mask self-assembly and provide protection against non-specific adsorption, opsonization, and RES uptake.

45. The self-assembly nanosystem of claim 37, wherein the blocking agent is conjugated to the monomeric unit or complementary binding moiety via a cleavable linker.

46. The self-assembly nanosystem of claim 37, wherein the monomeric unit further comprises a cargo entity.

47. The self-assembly nanosystem of claim 37, wherein the cargo entity is a diagnostic agent.

48. The self-assembly nanosystem of claim 47, wherein the diagnostic is selected from the group consisting of T2 contrast agent from the association of iron oxide nanoparticles;

x-ray, optical, or ultrasound contrast from the periodic structure of an assembled aggregate;

multi-modal imaging from the association of multiple imaging or contrast agents in a single aggregate; and

combinations thereof.

49. The self-assembly nanosystem of claim 37, wherein the cargo entity is a therapeutic agent.

50. The self-assembly nanosystem of claim 49, wherein therapeutic is selected from the group consisting of activation of a drug from association of prodrug and activator carrying nanoparticles;

activation of photo-dynamic therapy (PDT) from association of PDT and bioluminescent carrying nanoparticles;

creation of single magnetic moment aggregates from the assembly of super-paramagnetic moment nanoparticles for subsequent targeting of super-paramagnetic nanoparticles to the diseased site; and

combinations thereof.

51. The self-assembly nanosystem of claim 37, wherein all of the conjugates of the plurality of conjugates are identical to one another.

52. The self-assembly nanosystem of claim 37, wherein the plurality of conjugates comprises one or more populations of non-identical conjugates.

53. The self-assembly nanosystem of claim 52, wherein one population of non-identical conjugates comprises one complementary binding moiety, and another population of non-identical conjugates comprises a different complementary binding moiety.

54. The self-assembly nanosystem of claim 52, wherein one population of non-identical conjugates comprises one monomeric unit, and another population of non-identical conjugates comprises a different monomeric unit.

55. The self-assembly nanosystem of claim 52, wherein one population of non-identical conjugates comprises one blocking agent, and another population of non-identical conjugates comprises a different blocking agent.

56. The self-assembly nanosystem of claim 45, wherein all of the conjugates of the plurality of conjugates are identical to one another.

57. The self-assembly nanosystem of claim 45, wherein the plurality of conjugates comprises one or more populations of non-identical conjugates.

58. The self-assembly nanosystem of claim 57, wherein one population of non-identical conjugates comprises one cleavable linker, and another population of non-identical conjugates comprises a different cleavable linker.

59. The self-assembly nanosystem of claim 57, wherein one population of non-identical conjugates comprises one cargo entity, and another population of non-identical conjugates comprises a different cargo entity.

73. A method of treating a disease, condition, or disorder comprising administering the self-assembly nanosystem of claim 37 to a subject.

74. The method of claim 73, wherein the disease, condition, or disorder is a cell proliferative disorder.

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

76. The method of claim 73, wherein the disease, condition, or disorder has an inflammatory component.

60-72. -72. (canceled)

77-81. -81. (canceled)