# US 10,864,270 B2 · Nanostructured carriers for guided and targeted on-demand substance delivery

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- Number: US 10,864,270 B2
- Document ID: US10864270B2
- Status: Granted
- Kind: B2
- Application number: 16/111,090
- Filed: 2018-08-23
- Published: 2019-05-09
- Granted: 2020-12-15
- Earliest claimed: 2014-06-13
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Ratneshwar Lal; Preston B. Landon; Alexander Mo
- Web page: https://patentgrep.com/patent/US10864270B2

## CPC

- A61K 41/00: Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations}
- A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis}
- A61K 9/5115: {Inorganic compounds}
- A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5192: {Processes}
- A61K 38/05: Dipeptides
- A61K 41/0028: {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}
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- A61K 47/6941: {the form being a granulate or an agglomerate}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 2)

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

### Claim 4 (depends on 2)

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.

### Claim 5 (depends on 2)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 6)

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

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 8)

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.

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 1)

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.

### Claim 15 (depends on 14)

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

### Claim 16 (depends on 14)

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.

### Claim 17 (depends on 1)

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

### Claim 18 (depends on 13)

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.

### Claim 19 (depends on 16)

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.
