Systems and methods for treatment of disease via application of mechanical force by controlled rotation of nanoparticles inside cells

Patent metadata

Field	Value
Publication number	US-2016367668-A1
Application number	US-201615255611-A
Country	US
Kind code	A1
Filing date	Sep 2, 2016
Priority date	Mar 4, 2014
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present disclosure describes systems, apparatus, and methods for application of dynamic magnetic field (DMF) treatment to direct movement, and specifically rotation, of magnetic particles associated with a target structure, so that mechanical force is applied to the target structure. In certain embodiments, the present disclosure demonstrates application of DMF treatment to direct rotation about the axis in individual magnetic particles (e.g., superparamagnetic nanoparticles), effecting permeabilization and/or other disruption of membranes (e.g., cell membranes and/or intracellular membranes). In certain embodiments, the present disclosure describes use of an alternating current superconductor (ACSC) to greatly enhance the magnetic field amplitude so that the field can penetrate deeper into a body with sufficient amplitude to control movement of the nanoparticles within a working volume.

First claim

1 - 45 . (canceled)

46 . A method of applying mechanical force to a target structure, the method comprising:
exposing a target structure to magnetic particles so that the particles bind to the target structure; and applying a dynamic magnetic field (DMF) to the nanoparticles sufficient to induce movement of the particles.

47 . The method of claim 46 , wherein the induced movement comprises rotation.

48 . The method of claim 46 , wherein a mechanical force within a range of from about 1 fN to about 1 nN is applied to the target structure without the particles being significantly heated.

49 . The method of claim 46 , wherein the particles are or comprise a member selected from the group consisting of nanoparticles, superparamagnetic nanoparticles, iron oxide nanoparticles (“SPIONs”).

50 - 51 . (canceled)

52 . The method of claim 46 , wherein the magnetic particles are characterized by an iron oxide core.

53 . The method of claim 46 , wherein the particles are characterized in losing their magnetism when not exposed to an external magnetic field.

54 . The method of claim 46 , wherein the magnetic particles are associated with a targeting agent that specifically binds to the target structure.

55 . The method of claim 54 , wherein the targeting agent is covalently linked to the magnetic particles.

56 . (canceled)

57 . The method of claim 54 , wherein the targeting agent is or comprises a member selected from the group consisting of an antibody, a polypeptide, a small molecule, a glycan, a lipid, a nucleic acid that specifically binds to a target moiety in or on the target structure, and combinations thereof.

58 . The method of claim 57 , wherein the target moiety is or comprises a member selected from the group consisting of a polypeptide, a glycan, and a nucleic acid.

59 - 60 . (canceled)

61 . The method of claim 46 , wherein the target structure is or comprises a member selected from the group consisting of a cell membrane, a tumor-associated marker, an ion channel, an intracellular membrane, a lysosomal membrane, an intracellular entity, and a tumor-associated entity.

62 - 66 . (canceled)

67 . The method of claim 61 , wherein the intracellular entity is or comprises an organelle.

68 . The method of claim 67 , wherein the organelle is selected from the group consisting of the endoplasmic reticulum (ER), the golgi apparatus, the mitochondria, and combinations thereof.

69 . The method of claim 66 , wherein the intracellular entity is or comprises a member selected from the group consisting of an organelle, a component of transcription machinery, a splicosome, and a ribosome.

70 . The method of claim 66 , wherein the target structure is or comprises a lysosomal membrane and the magnetic particles are associated with a targeting agent that specifically binds to the target structure.

71 . The method of claim 70 , wherein the targeting agent is covalently linked to the magnetic particles.

72 . The method of claim 71 , wherein the targeting agent specifically binds to a target moiety on the surface of the lysosomal membrane.

73 . The method of claim 72 , wherein the target moiety is or comprises LAMP-1 (CD107a), LAMP-2 (CD107b), or LAMP-3 (CD63).

74 . The method of claim 46 , wherein the step of exposing comprises exposing the target structure to the magnetic particles so that the nanoparticles bind to the target structure with a density sufficient to apply a desired force across a relevant area.

75 . The method of claim 74 , wherein the step of exposing comprises exposing the target structure to the magnetic particles so that, on average, about 1 to about 60 magnetic particles become bound to each lysosome.

76 . The method of claim 75 , wherein the step of exposing comprises exposing the target structure to the magnetic particles so that, on average, about 10 to about 50 magnetic particles become bound to each lysosome.

77 . The method of claim 75 , wherein the step of exposing comprises exposing the target structure to the magnetic particles so that, on average, about 30 magnetic particles become bound to each lysosome.

78 . The method of claim 46 , wherein the step of applying DMF treatment comprises applying a DMF field with a strength within the range of about 1 mT to 5 T.

79 . The method of claim 46 , wherein the step of applying DMF treatment comprises applying a DMF field with a reach selected from the group consisting of within the range of about 1 mm to about 1 cm, of at least 1 cm, of at least 2 cm to 5 cm, of at least 10 cm, and of at least 50 cm.

80 - 84 . (canceled)

85 . The method of claim 61 , wherein the tumor-associated entity is or comprises a member selected from the group consisting of a cell-surface entity and an intracellular entity.

86 - 95 . (canceled)

Assignees

• Memorial Sloan Kettering Cancer Center

Inventors

• Kircher Moritz F
• Renström Erik
• Koch Martin
• Stetter Ernst
• Reis Thomas

Classifications

• A61N2/02 Primary

  using magnetic fields produced by coils, including single turn loops or electromagnets (A61N2/12 takes precedence) · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K41/0028 Primary

  Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds · CPC title

• A61K47/48538

  Human Necessities · mapped topic

• A61K41/00 Primary

  Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations} · CPC title