SELF-ASSEMBLED, MICROPATTERNED, AND RADIO FREQUENCY (RF) SHIELDED BIOCONTAINERS AND THEIR USES FOR REMOTE SPATIALLY CONTROLLED CHEMICAL DELIVERY

• US 20090311190A1
• Filed: 06/25/2007
• Published: 12/17/2009
• Est. Priority Date: 06/23/2006
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Ye, Hongke, Leong, Timothy Gar-Ming, Gracias, David H.
• Granted Patent: US 8,246,917 B2
• Time in Patent Office: Days
• US Class Current: 424/9.300
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/062 using magnetic field
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 6/032 Transmission computed tomography [CT]
• CPC Class Codes: A61K 49/1821 coated or functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: G01R 33/286 involving passive visualization of interventional instruments, i.e. making the instrument visible as part of the normal MR process
• CPC Class Codes: Y10S 977/70 Nanostructure
• CPC Class Codes: Y10S 977/902 Specified use of nanostructure
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/905 Specially adapted for travel through blood circulatory system
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10T 428/13 Hollow or container type article [e.g., tube, vase, etc.]
• CPC Class Codes: Y10T 428/1352 Polymer or resin containing [i.e., natural or synthetic]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

The present invention relates to a nanoscale or microscale particle for encapsulation and delivery of materials or substances, including, but not limited to, cells, drugs, tissue, gels and polymers contained within the particle, with subsequent release of the therapeutic materials in situ, methods of fabricating the particle by folding a 2D precursor into the 3D particle, and the use of the particle in in-vivo or in-vitro applications The particle can be in any polyhedral shape and its surfaces can have either no perforations or nano/microscale perforations The particle is coated with a biocompatible metal, e g gold, or polymer e g parvlene, layer and the surfaces and hinges of the particle are made of any metal or polymer combinations.

Claims

1. A three-dimensional particle comprising a plurality of two-dimensional faces capable of self-folding to form a hollow interior, wherein a size of the particle is microscale or nanoscale.

1a. a. A particle of claim 1, wherein the size of the particle ranges from 1 nm to 2 mm.

2. The particle of claim 1, wherein the particle further comprises at least one hinge.

3. The particle of claim 2, wherein the hinge comprises any liquefiable material.

4. The particle of claim 2, wherein the hinge is selected from the group consisting of a polymer, a gel, glass or a metal.

5. The particle of claim 1, wherein the particle has surfaces forming a polyhedral shape.

6. The particle of claim 5, wherein the shape is a cube.

7. The particle according to claim 1, wherein the two-dimensional faces are patterned with perforations or pores.

8. The particle according to claim 7, wherein the perforations or pores are created photolithographically, electrolytically, or by using electron beam lithography.

9. The particle according to claim 7, wherein the perforations or pores have a size from about 0.1 nm to about 1 cm.

10. The particle of claim 9, wherein the perforations or pores have a size from about 10 nm to about 1 cm.

11. The particle according to claim 1, wherein the particle is fabricated from at least one material selected from the group consisting of a metal, a polymer, a glass, a semiconductor, an insulator, and combinations thereof.

12. The particle according to claim 1, further comprising active electronic or semiconductor components including transistors, sensors, actuators, light emitting diodes, photodiodes and solar cells,

13. The particle according to claim 11, wherein the metal is copper or nickel.

14. The particle according to claim 1, wherein the particle is a Faraday cage.

15. The particle according to claim 1, wherein the particle is coated with a biocompatible material.

16. The particle according, to claim 15, wherein the particle is associated with a biosensor.

17. The particle according to claim 15, wherein the biocompatible material is a metal, a polymer, or a combination thereof.

18. The particle according to claim 1, further comprising at least one substance encapsulated within the particle.

19. The particle according to claim 18, wherein perforations or pores in the two-dimensional faces of the particle allow release of the contents of the particle.

20. The particle of claim 18, wherein the substance is a therapeutic agent.

21. The particle according to claim 20, wherein the therapeutic agent is selected from the group consisting of a cell, a chemical or biological agent, a pharmaceutical agent, a composition, a tissue, a gel, and a polymer.

22. The particle according to claim 1, wherein the particle is administered to a subject and location of the particle in the subject is non-invasively tracked by magnetic resonance imaging (MRI) or CAT scan (CT).

23. The particle according to claim 22, wherein the particle is imaged with negative contrast relative to background or positive contrast relative to background.

24. The particle of claim 20, additionally comprising a radio frequency tag,

25. The particle of claim 24, wherein the substance may be released upon the particle'"'"'s exposure to a pre-selected frequency.

26. The particle of claim 12, wherein the substance may be released upon the particle'"'"'s exposure to electromagnetic radiation.

27. The particle of claim 26, wherein the electromagnetic radiation is triggered remotely.

28. The particle of claim 26, wherein the electromagnetic radiation ranges from 1 KHz to 1 Peta Hz.

29. The particle of claim 20, wherein the substance may be released upon the particle'"'"'s exposure to inductive heating.

30. The particle of claim 29, wherein the inductive heating is triggered remotely.

40. A method of imaging a particle according to claim 1 that has been implanted into a subject, the method comprising the steps of:

(i) loading the hollow interior of the particle with at least one substance to form a loaded particle;

(ii) administering the loaded particle to the subject; and

(iii) noninvasively tracking the particle of step (ii) in the subject by magnetic resonance imaging.

41. The particle according to claim 40 wherein perforations or pores in the two-dimensional faces of the particle allow release of the substance in the hollow interior.

42. The particle according to claim 40, wherein the at least one substance of step (i) is a therapeutic agent.

43. The particle according to claim 42, wherein the therapeutic agent is selected from the group consisting of a cell, a pharmaceutical agent, a composition, a tissue, a gel, and a polymer.

44. A method of treating a condition comprising introducing into an animal in need of treatment at least one particle of claim 1 encapsulating a composition, wherein the composition is released through one or more pores within the particle into the mammal in an amount sufficient to treat the condition.

45. The method of claim 44, wherein the pharmaceutical composition is contained within one or more microbeads.

46. The method of claim 44, wherein the condition is diabetes, and the composition is one or more insulin-secreting cells.

47. A method for imaging a particle of claim 1 that has been introduced into a mammal wherein the method comprises using magnetic resonance imaging.

48. A method for targeting the particle of claim 1 to a cell within a subject comprising the steps of:

a) attaching to the particle an antibody against an antigen specific to the cell;

b) introducing the particle into the mammal,

wherein the particle is targeted to the cell.

49. A method of delivering one or more particles of claim 21 to a subject, wherein the particle is programmed to remotely release one or more reactants at a specific time and a specific location.

50. A method of claim 49, wherein the particle is remotely guided and imaged using MRI or CT.

51. A method of claim 50, wherein the particle is capable of releasing a contrast agent or of providing contrast to allow MRI or CT imaging of its contents or of substances within its vicinity.

31. A method of fabricating a three-dimensional particle comprising a multitude of two-dimensional faces that form a hollow polyhedral shape and containing a fillable center chamber, the method comprising the steps:

(a) fabricating a multitude of two dimensional faces;

(b) patterning the fabricated two-dimensional faces;

(c) patterning at least one image on the patterned two dimensional face to form a hinged edge;

(d) joining a hinged edge of a first patterned two dimensional face to a hinged edge of a second patterned two dimensional face to form a hinged joint;

(e) repeating step (d) to form a two dimensional precursor template having hinged joints between adjacent two dimensional faces; and

(f) liquefying the hinges of the two-dimensional template using heat to initiate self-folding;

thereby inducing the three-dimensional particle to self-assemble.

32. The method according to claim 31, wherein the hinges of step (c) comprise a material that can be liquefied.

33. The method according to claim 32, wherein the material is a solder, a metallic alloy, a polymer or a glass.

34. The method according to claim 31, step (a) further comprising the steps

(i) spinning a sacrificial film on a substrate to form a first layer;

(ii) layering a conductive second layer on the first layer; and

(iii) patterning the layered substrate by photolithography.

35. The particle according to claim 31, wherein the particle has a size that is microscale or nanoscale.

36. The particle according to claim 31, wherein in step (b) the two-dimensional faces are patterned with perforations or pores.

37. The particle according to claim 36, wherein the perforations or pores are created photolithographically.

38. The particle according to claim 36, wherein the perforations or pores have a size from about 0.1 nm to about 100 microns.

39. The particle according to claim 31, wherein the particle is a Faraday cage.

52. A method of conducting non-invasive biopsy or microsurgery, comprising directing the particles to a site within a subject using remote means, allowing the particle to capture one or more substances from the site, and obtaining the substance from the particle, thereby non-invasively conducting biopsy or microsurgery.