Enzyme directed assembly of particle theranostics
AssigneeThe Regents of the University of California
InventorsNathan C. Gianneschi, Michael Hahn, Robert Mattrey
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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.
Claims26
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.
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.
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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.
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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.
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.
-28. (canceled)
Dependencies are inferred from the claim text.