# US 2023/0067643 A1 · Iron oxide nanoparticle for targeted chemo-immunotherapy

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- Number: US 2023/0067643 A1
- Document ID: US20230067643A1
- Status: Published application
- Kind: A1
- Application number: 17/821,794
- Filed: 2022-08-23
- Published: 2023-03-02
- Earliest claimed: 2021-08-26
- Assignees: University of Washington
- Applicants: University of Washington
- Inventors: Miqin Zhang; Qingxin Mu; Guanyou Lin
- Web page: https://patentgrep.com/patent/US20230067643A1

## CPC

- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- 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

## Abstract

Multifunctional nanoparticle for targeted therapeutic drug delivery, comprising (a) an iron oxide core having silica-polyethylene glycol coupled thereto to provide an iron oxide coated core, (b) a cytotoxic agent reversibly associated with the coated core; (c) an immunomodulating agent reversibly associate with the coated core; and (d) a tumor targeting agent associated with the coated core. Methods for using the nanoparticle to treat cancers and methods for making the nanoparticle.

## Claims

### Claim 1

A nanoparticle for targeted therapeutic drug delivery, comprising:
(a) an iron oxide core having silica-polyethylene glycol coupled thereto to provide an iron oxide coated core;
(b) a cytotoxic agent reversibly associated with the coated core;
(c) an immunomodulating agent reversibly associated with the coated core; and
(d) a tumor targeting agent associated with the coated core.

### Claim 2 (depends on 1)

The nanoparticle of claim 1, wherein the cytotoxic agent forms a first layer surrounding the coated core.

### Claim 3 (depends on 1)

The nanoparticle of claim 1, wherein the immunomodulating agent forms a second layer surrounding the first layer.

### Claim 4 (depends on 1)

The nanoparticle of claim 1, wherein the cytotoxic agent is a chemotherapeutic drug.

### Claim 5 (depends on 1)

The nanoparticle of claim 1, wherein the cytotoxic agent is selected from the group consisting of doxorubicin, daunorubicin, epirubicin, idarubicin, irinotecan, topotecan, mitoxantrone, vinblastine, cisplatin, and mixtures thereof.

### Claim 6 (depends on 1)

The nanoparticle of claim 1, wherein the immunomodulating agent is an agonist of a receptor in innate or adaptive immune response.

### Claim 7 (depends on 1)

The nanoparticle of claim 1, wherein the immunomodulating agent is polyinosinic:polycytidylic acid (PolyIC).

### Claim 8 (depends on 1)

The nanoparticle of claim 1, wherein the tumor targeting agent is a tumor target ligand or peptide against triple negative breast cancer, a tumor target ligand against tumor vasculature endothelia cells, a tumor target ligand folic acid against folate receptor, or a transferrin against transferrin receptors overexpressed by breast cancer.

### Claim 9 (depends on 1)

The nanoparticle of claim 1, wherein the cytotoxic agent is doxorubicin, the immunomodulating agent is polyinosinic:polycytidylic acid (PolyIC), and the tumor targeting agent is endoglin-binding peptide (EBP).

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

A method for treating breast cancer, comprising administering a therapeutically effective amount of a nanoparticle of claim 1 to a subject in need thereof.

### Claim 12 (depends on 11)

The method of claim 11, wherein the breast cancer is metastatic breast cancer.

### Claim 13 (depends on 11)

The method of claim 11, wherein the breast cancer is triple negative breast cancer (TNBC).

### Claim 14 (depends on 11)

The method of claim 11, wherein administering a therapeutically effective amount of the nanoparticle results in direct tumor cell killing.

### Claim 15 (depends on 11)

The method of claim 11, wherein administering a therapeutically effective amount of the nanoparticle results in dendritic cell-initiated innate immune response.

### Claim 16 (depends on 11)

The method of claim 11, wherein administering a therapeutically effective amount of the nanoparticle results in T cell-mediated adaptive immune response.

### Claim 17 (depends on 11)

The method of claim 11, wherein administering a therapeutically effective amount of the nanoparticle results in direct tumor cell killing, dendritic cell-initiated innate immune response, and T cell-mediated adaptive immune response.

### Claim 18 (depends on 1)

A method for inhibiting breast cancer tumor growth, comprising administering to a subject in need thereof an amount of a nanoparticle of claim 1 effective to inhibit tumor growth.

### Claim 19 (depends on 1)

A method for inhibiting breast cancer metastasis, comprising administering to a subject in need thereof an amount of a nanoparticle of claim 1 effective to inhibit metastasis.

### Claim 20

A method for making a multifunctional nanoparticle, comprising:
(a) forming a layer of silica-polyethylene glycol surrounding an iron oxide core to provide a coated iron oxide core;
(b) associating a tumor targeting agent to the coated core;
(c) forming a first layer of a cytotoxic agent surrounding the coated core; and
(d) forming a second layer of an immunomodulating agent surrounding the first layer to provide a nanoparticle comprising a tumor targeting agent, a cytotoxic agent, and an immunomodulating agent.
