# US 2023/0405362 A1 · Systems and methods for targeted neuroregeneration

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- Number: US 2023/0405362 A1
- Document ID: US20230405362A1
- Status: Published application
- Kind: A1
- Application number: 18/459,591
- Filed: 2023-09-01
- Published: 2023-12-21
- Earliest claimed: 2021-03-02
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University In the City of New York
- Inventors: Elisa KONOFAGOU; Antonios POULIOPOULOS
- Web page: https://patentgrep.com/patent/US20230405362A1

## CPC

- A61N 7/00: Ultrasound therapy (lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 {; using ultrasound for introducing media into the body A61M37/0092})
- 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 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- A61K 49/223: {Microbubbles, hollow microspheres, free gas bubbles, gas microspheres}
- A61M 37/0092: {using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis}
- A61N 2007/0026: {Stimulation of nerve tissue}
- A61N 2007/0039: {using microbubbles}
- A61N 2007/0052: {using the same transducer for therapy and imaging}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- 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)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

The present subject matter relates to techniques for treating a neurodegenerative disease. The disclosed system can include a transducer for stimulating a target tissue with focused ultrasound (FUS) and at least one nanocup. The transducer induces the FUS with a predetermined parameter to open the target tissue. The nanocup can include at least one gas pocket within a cavity of the nanocup and an effective amount of an active agent for neuroregeneration.

## Claims

### Claim 1

A system for treating a neurodegenerative disease, comprising:
a transducer for stimulating a target tissue with focused ultrasound (FUS), wherein the transducer induces the FUS with a predetermined parameter to open the target tissue; and
at least one nanocup, wherein the nanocup comprises at least one gas pocket within a cavity of the nanocup, wherein the nanocup comprises an effective amount of an active agent for neuroregeneration.

### Claim 2 (depends on 1)

The system of claim 1, wherein the nanocup is configured to react to the FUS with the predetermined parameter.

### Claim 3 (depends on 1)

The system of claim 1, wherein a size of the nanocup is less than about 100 nm.

### Claim 4 (depends on 1)

The system of claim 1, further comprising microbubbles configured to open the target tissue through cavitation.

### Claim 5 (depends on 5)

The system of claim 5, wherein the microbubbles comprise at least one gas-filled cavity configured to act as a contrast agent in pulse inversion or full-waveform inversion ultrasound imaging.

### Claim 6 (depends on 1)

The system of claim 1, wherein the active agent comprises a brain-derived neurotrophic factor (BDNF).

### Claim 7 (depends on 6)

The system of claim 6, wherein the BDNF is covalently conjugated with the nanocup.

### Claim 8 (depends on 1)

The system of claim 1, wherein the nanocup is configured to release the active agent after the FUS with the predetermined parameter is applied to the nanocup.

### Claim 9 (depends on 1)

The system of claim 1, further comprising a processor configured to map a spatial distribution of a cavitation activity of the nanocup through passive acoustic mapping.

### Claim 10 (depends on 1)

The system of claim 1, wherein the nanocup comprises a PEG layer that is configured to conjugate with a protein and/or an antibody.

### Claim 11 (depends on 1)

The system of claim 1, wherein the nanocup comprises an anti-Aβ antibody.

### Claim 12 (depends on 11)

The system of claim 11, wherein the nanocup has an Aβ binding efficiency more than about 80%.

### Claim 13 (depends on 1)

The system of claim 1, wherein the predetermined parameter to open the target tissue is selected from the group consisting of a center frequency, an outer diameter, an inner diameter, a radius of curvature, and a combination thereof.

### Claim 14 (depends on 12)

The system of claim 12, wherein the center frequency ranges from about 0.2 MHz to about 0.35 MHZ.

### Claim 15 (depends on 1)

The system of claim 1, further comprising a navigation guidance device configured to locate and/or monitor the target tissue, wherein the navigation guidance device comprises a cavitation detector configured to detect the microbubble cavitation and/or the nanocup cavitation.

### Claim 16

A method for treating a neurodegenerative disease, comprising:
administering at least one nanocup to a target tissue, wherein the nanocup comprises at least one gas pocket within a cavity of the nanocup, wherein the nanocup comprises an effective amount of an active agent for neuroregeneration; and
applying FUS using a transducer, wherein the transducer induces the FUS with a predetermined parameter to open the target tissue, the predetermined parameter is selected from the group consisting of a center frequency, an outer diameter, an inner diameter, a radius of curvature, and a combination thereof.

### Claim 17 (depends on 16)

The method of claim 16, further comprising imaging spatial distribution of the at least one nanocup through a full-waveform inversion imaging at various time points.

### Claim 18 (depends on 16)

The method of claim 16, further comprising administering at least one microbubble, and applying a low-pressure FUS to increase a permeability of the target tissue, wherein the low-pressure ranges from about about 0.1 MPa to about 1 MPa.

### Claim 19

The method of 18, wherein the applying FUS comprises applying a high-pressure FUS to trigger a release of an active agent from the nanocup, wherein the high-pressure ranges from about about 0.5 MPa to about 2 MPa.

### Claim 20 (depends on 18)

The method of claim 18, wherein the target tissue comprises a cortical brain structure, a subcortical brain structure, a hippocampus, a caudate putamen, a brain parenchyma, or a combination thereof.