Nanostructured carriers for guided and targeted on-demand substance delivery

Patent metadata

Field	Value
Publication number	US-10864270-B2
Application number	US-201816111090-A
Country	US
Kind code	B2
Filing date	Aug 23, 2018
Priority date	Jun 13, 2014
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

Methods, systems, and devices are disclosed for fabricating and implementing nanoscale and microscale structured carriers to provide guided, targeted, and on-demand delivery of molecules and biochemical substances for a variety of applications including diagnosis and/or treatment (theranostics) of diseases in humans and animals. In some aspects, a nanostructure carrier can be synthesized in the form of a nanobowl, which may include an actuatable capping particle that can be opened (and in some implementations, closed) on demand. In some aspects, a nanostructure carrier can be synthesized in the form of a hollow porous nanoparticle with a functionalized interior and/or exterior to attach payload substances and substances for magnetically guided delivery and controlled release of substance payloads.

First claim

What is claimed is:

1. A method to fabricate a carrier structure, comprising:
forming a template by attaching a plurality of mask particles on a core particle, the mask particles forming masked regions on the exterior surface of the core particle where they attach;
attaching nanoparticles to unmasked surface of the template, wherein the mask particles prevent the nanoparticles to attach to the masked regions of the exterior surface;
producing a shell structure over the unmasked surface of the template by forming a coating over the unmasked surface by material growth of the attached nanoparticles;
prior to removing the masking particles from the template, forming an outer layer around the shell structure to produce a bi-layered shell structure; and
producing a porous carrier structure by removing the mask particles from the template, wherein the removed mask particles form openings extending between an external surface of the bi-layered shell structure and the exterior surface of the core particle.

2. The method of claim 1 , wherein the mask particles attach to the core particle by electrostatic interaction.

3. The method of claim 2 , wherein the core particle includes cationic silica and the mask particles include polystyrene.

4. The method of claim 2 , wherein the core particle includes a size of 1 μm or less, and the mask particles include a size of 100 nm or less.

5. The method of claim 2 , wherein the mask particles include polystyrene particles with an outer functionalized coating having a carboxylated terminus.

6. The method of claim 1 , wherein the nanoparticles include gold nanoparticles.

7. The method of claim 6 , wherein the gold nanoparticles include a size of 5 nm or less.

8. The method of claim 1 , wherein the forming the coating includes immersing the template in a solution containing the material of the nanoparticles to cause nucleation and growth on the unmasked surface of the template.

9. The method of claim 8 , wherein the nanoparticles include gold nanoparticles and the solution includes gold hydroxide, the forming including producing gold seeds that nucleate into a gold shell structure.

10. The method of claim 1 , wherein the porous carrier structure includes an outer gold porous shell formed over a silica core particle.

11. The method of claim 1 , wherein the removing the mask particles from the template includes dissolving the mask particles in an organic solvent.

12. The method of claim 1 , further comprising:
attaching magnetic nanoparticles to an outside surface of the porous carrier structure.

13. The method of claim 1 , further comprising:
loading the porous carrier structure with a molecular payload, wherein the loading includes functionalizing a surface of the bi-layered shell structure or the core particle exposed through the openings, or both, with attachment molecules capable of linking the molecular payload.

14. The method of claim 1 , further comprising:
removing at least a portion of the core particle from the template to produce a hollow, porous carrier structure.

15. The method of claim 14 , further comprising:
attaching magnetic nanoparticles to a surface of the hollow porous carrier structure.

16. The method of claim 14 , further comprising:
loading the hollow porous carrier structure with a molecular payload, wherein the loading includes functionalizing an interior surface or an outside surface of the hollow porous carrier structure with attachment molecules capable of linking the molecular payload.

17. The method of claim 1 , wherein the outer layer includes silica, and the shell structure includes gold.

18. The method of claim 13 , wherein the molecular payload is capable of being controllably released based on a stimulus including at least one of a chemical substance, an emission of light, a change in pH environment, or a change in temperature to cause detachment of the molecular payload from the carrier structure.

19. The method of claim 16 , wherein the molecular payload is capable of being controllably released based on a stimulus including at least one of a chemical substance, an emission of light, a change in pH environment, or a change in temperature to cause detachment of the molecular payload from the carrier structure.

Assignees

• Univ California

Inventors

• Lal Ratneshwar
• Landon Preston B
• Mo Alexander

Classifications

• A61K9/0009 Primary

  involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis · CPC title

• A61K41/0028

  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

• A61K47/6923

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title

• A61K38/05

  Dipeptides · CPC title

• A61K47/6925

  the form being a microcapsule, nanocapsule, microbubble or nanobubble · CPC title