# US 2023/0405145 A1 · Iron oxide nanoparticle for suppressing drug-resistant gene for the treatment of glioblastoma

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- Number: US 2023/0405145 A1
- Document ID: US20230405145A1
- Status: Published application
- Kind: A1
- Application number: 18/248,139
- Filed: 2021-10-06
- Published: 2023-12-21
- Earliest claimed: 2020-10-08
- Assignees: University of Washington
- Applicants: University of Washington
- Inventors: Miqin Zhang; Richard G. Ellenbogen; Kui Wang; Forrest M. Kievit; John R. Silber; Zachary Stephen; Peter A. Chiarelli
- Web page: https://patentgrep.com/patent/US20230405145A1

## CPC

- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- A61P 35/00: Antineoplastic agents
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A nanoparticle for targeted siRNA delivery comprising an iron oxide core and a chitosan-polyethylene glycol-polyethylenimine copolymer coating surrounding the core, chlorotoxin covalently coupled to the coating, and an siRNA reversibly associated to the coating by non-covalent interaction. Methods for making the nanoparticle and methods for using the nanoparticle to suppress the expression of O6-methylguanine-DNA methyltransferase (MGMT), treating brain cancer, and killing cancer stem cells.

## Claims

### Claim 1

A nanoparticle for targeted siRNA delivery, comprising:
(a) an iron oxide core and a chitosan-polyethylene glycol-polyethylenimine copolymer coating surrounding the core;
(b) chlorotoxin covalently coupled to the coating; and
(c) an siRNA reversibly associated to the coating by non-covalent interaction.

### Claim 2

A nanoparticle for targeted siRNA delivery, consisting of:
(a) an iron oxide core and a chitosan-polyethylene glycol-polyethylenimine copolymer coating surrounding the core;
(b) chlorotoxin covalently coupled to the coating; and
(c) an siRNA reversibly associated to the coating by non-covalent interaction.

### Claim 3 (depends on 1)

The nanoparticle of claim 1, wherein the iron oxide core has a size from about 4 to about 12 nm.

### Claim 4 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has a size from about 35 to about 80 nm.

### Claim 5 (depends on 1)

The nanoparticle of claim 1, wherein the chlorotoxin is present in an amount from 1 to about 200 chlorotoxins per nanoparticle.

### Claim 6 (depends on 1)

The nanoparticle of claim 1, wherein the siRNA is present in an amount from about 100 to about 400 siRNAs per nanoparticle.

### Claim 7 (depends on 1)

The nanoparticle of any-one-of-claims-1-6 claim 1, wherein the siRNA reduces the expression of O6-methylguanine-DNA methyltransferase in a subject.

### Claim 8 (depends on 1)

The nanoparticle of claim 1, wherein the siRNA is siMGMT.

### Claim 9 (depends on 1)

A pharmaceutical composition comprising the nanoparticle of claim 1 and a pharmaceutically acceptable carrier.

### Claim 10 (depends on 9)

The pharmaceutical composition of claim 9 formulated for intravenous injection.

### Claim 11 (depends on 7)

A method for suppressing the expression of O6-methylguanine-DNA methyltransferase in a subject, comprising administering an effective amount of a nanoparticle of claim 7 to a subject in need thereof.

### Claim 12 (depends on 7)

A method for treating brain cancer in a subject, comprising administering a therapeutically effective amount of a nanoparticle of claim 7 to a subject in need thereof.

### Claim 13 (depends on 12)

The method of claim 12, wherein the brain cancer is a glioblastoma.

### Claim 14 (depends on 12)

The method of claim 12, wherein the brain cancer is glioblastoma multiforme.

### Claim 15 (depends on 7)

A method for killing cancer stem cells in a subject, comprising administering a therapeutically effective amount of a nanoparticle of claim 7 to a subject in need thereof.

### Claim 16 (depends on 1)

A method for magnetic resonance imaging a tumor in a subject, comprising administering an effective amount of a nanoparticle of claim 1 to a subject in need thereof.

### Claim 17 (depends on 11)

The method of claim 11, wherein the nanoparticle is administered intravenously.

### Claim 18 (depends on 11)

The method of claim 11, wherein the subject is a human.

### Claim 19

A method for making a nanoparticle for targeted siRNA delivery, comprising contacting an siRNA with an iron oxide nanoparticle, wherein the iron oxide nanoparticle comprises an iron oxide core and a chitosan-polyethylene glycol-polyethylenimine copolymer coating surrounding the core, and a targeting agent covalently coupled to the coating.

### Claim 20 (depends on 19)

The method of claim 19, wherein the targeting agent is chlorotoxin.

### Claim 21

(canceled)