# US 2014/0193342 A1 · Enzyme directed assembly of particle theranostics

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0193342 A1
- Document ID: US20140193342A1
- Status: Published application
- Kind: A1
- Application number: 14/125,273
- Filed: 2012-06-11
- Published: 2014-07-10
- Earliest claimed: 2011-06-10
- Assignees: The Regents of the University of California
- Inventors: Nathan C. Gianneschi; Michael Hahn; Robert Mattrey
- Web page: https://patentgrep.com/patent/US20140193342A1

## CPC

- A61K 49/128: {comprising multiple complex or complex-forming groups, being either part of the linear polymeric backbone or being pending groups covalently linked to the linear polymeric backbone}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 47/585: {Ion exchange resins, e.g. polystyrene sulfonic acid resin}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)}
- A61K 49/0043: {Fluorescein, used in vivo}
- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- A61K 49/0082: {micelle, e.g. phospholipidic micelle and polymeric micelle}
- A61K 49/1809: {Micelles, e.g. phospholipidic or polymeric micelles}
- 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

Provided herein is a method for enzymatically triggered assembly of polymeric nanostructures for detection of cancer-associated enzymes in vivo. By detecting enzymatic signals associated with disease, one can sensitively determine the site, and extent of disease within a patient.

## Claims

### Claim 1

A hydrophilic polymer probe comprising:
(i) a hydrophilic polymer probe with an enzyme cleavable moiety and at least one of (ii) or (iii), wherein
(ii) is a visualizable label; and
(iii) is a therapeutic agent and a targeting moiety.

### Claim 2 (depends on 1)

The hydrophilic polymer probe of claim 1, wherein the visualizable label is a fluorophore, Gd3+ reporter, or a combination thereof.

### Claim 3 (depends on 1)

The hydrophilic polymer probe of claim 1, wherein the therapeutic agent is selected from the group comprising doxorubicin, paclitaxel, cisplatin, a tyrosine kinase inhibitor, a topoisomerase inhibitor, an alkylating agent, an anthracycline, and a chemotherapeutic agent.

### Claim 4 (depends on 1)

The hydrophilic polymer probe of claim 1, wherein the targeting moiety is peptide-based sequence or a nucleic acid-based sequence.

### Claim 5

A method of detecting diseased tissue in a subject comprising:
(a) administering a hydrophilic polymer probe to the subject;
wherein the hydrophilic polymer probe comprises a hydrophilic polymer with an enzyme cleavable moiety and a visualizable label;
wherein the enzyme cleavable moiety is cleaved by an enzyme present in a diseased tissue, and
wherein cleavage of the enzyme cleavable moiety in the hydrophilic polymer probe causes the hydrophilic polymer probe to self-assemble into an amphiphilic polymer aggregate comprising an amphiphilic polymer and the visualizable label; and
(b) determining the presence or absence of amphiphilic polymer aggregate in a tissue in the subject, wherein the presence of amphiphilic polymer aggregate in the tissue indicates that the tissue is diseased; and
(c) detecting diseased tissue in the subject where amphiphilic polymer aggregate is present.

### Claim 6

(canceled)

### Claim 7 (depends on 5)

The method of claim 5, wherein the cancer-associated enzyme is a matrix metalloprotease or matrix metalloproteinase (MMP).

### Claim 8

(canceled)

### Claim 9 (depends on 5)

The method of claim 5, wherein the enzyme is a protease or a nuclease.

### Claim 10 (depends on 5)

The method of claim 5, wherein the enzyme cleavable moiety is a peptide structure or a DNA structure.

### Claim 11

(canceled)

### Claim 12 (depends on 5)

The method of claim 5, wherein the diseased tissue is a MMP-mediated malignancy, sarcoma, or metastasis.

### Claim 13 (depends on 5)

The method of claim 5, wherein the visualizable label is a fluorophore, Gd3+ reporter, or a combination thereof.

### Claim 14 (depends on 5)

The method of claim 5, wherein the amphiphilic polymer aggregate forms a micelle.

### Claim 15

A method of treating a subject having cancer, the method comprising:
(a) administering a hydrophilic polymer probe to the subject;
wherein the hydrophilic polymer probe comprises a hydrophilic polymer with an enzyme cleavable moiety, a therapeutic agent, and a targeting moiety,
wherein the enzyme cleavable moiety is cleaved by an enzyme present in a diseased tissue, and;
wherein cleavage of the enzyme cleavable moiety in the hydrophilic polymer probe causes the hydrophilic polymer probe to self-assemble into an amphiphilic polymer aggregate comprising an amphiphilic polymer and the therapeutic agent;
(b) allowing the targeting moiety to localize the hydrophilic polymer probe to a targeted tissue in the subject as directed by the targeting moiety; and
(c) treating a subject with cancer in the subject by exposing the targeted tissue to the amphiphilic polymer aggregate.

### Claim 16 (depends on 15)

The method of claim 15, wherein the enzyme cleavable moiety is cleaved by a protease, a nuclease, a matrix metalloprotease or matrix metalloproteinase (MMP).

### Claim 17

(canceled)

### Claim 18 (depends on 15)

The method of claim 15, wherein the cancer is a MMP-mediated malignancy, sarcoma, or metastasis.

### Claim 19 (depends on 15)

The method of claim 15, wherein the enzyme is a protease, nuclease, matrix metalloprotease, or MMP.

### Claim at position 20

-21. (canceled)

### Claim 22 (depends on 15)

The method of claim 15, wherein the therapeutic agent is selected from the group comprising doxorubicin, paclitaxel, cisplatin, a tyrosine kinase inhibitor, a topoisomerase inhibitor, an alkylating agent, an anthracycline, and a chemotherapeutic agent.

### Claim 23 (depends on 15)

The method of claim 15, wherein the amphiphilic polymer aggregate forms a micelle.

### Claim 24 (depends on 15)

The method of claim 15, wherein the targeting moiety is peptide-based sequence or a nucleic acid-based sequence.

### Claim 25

An enzymatically-generated, self-assembled amphiphilic polymer aggregate comprising: an amphiphilic polymer comprising a hydrophilic cryptic-amphiphile associated with a polypeptide cleaved by a matrix metalloproteinase, and a visualizable label.

### Claim 26

An enzymatically-generated self-assembled amphiphilic polymer aggregate comprising: an amphiphilic polymer comprising a hydrophilic cryptic-amphiphile associated with a nucleic acid structure cleaved by an enzyme, and a visualizable label.

### Claim at position 26

-28. (canceled)