Systems and methods for targeted imaging and ablation of cardiac cells

Patent metadata

Field	Value
Publication number	US-2020188514-A1
Application number	US-201916708804-A
Country	US
Kind code	A1
Filing date	Dec 10, 2019
Priority date	Apr 23, 2012
Publication date	Jun 18, 2020
Grant date	—

Abstract

The present invention relates to nanoparticles. In particular, the present invention provides nanoparticles for clinical (e.g., targeted therapeutic), diagnostic (e.g., imaging), and research applications in the field of cardiology. For example, in some embodiments, the present invention provides a method of treating (e.g., ablating) cardiac tissue, comprising: a) contacting an animal with a nanoparticle comprising a matrix, a toxic (e.g., ablative) agent (e.g., sonosensitizer, chemotherapeutic agent (e.g., doxorubicin or cisplatin), or photosensitizer), and a cardiac targeting moiety; and b) administering an activator of the toxic agent (e.g., light, chemical (e.g., pharmaceutical agent) or ultrasound) to at least a portion of the cardiac tissue (e.g., heart) of the animal to activate the toxic agent.

First claim

1 - 23 . (canceled)

24 . A composition, comprising: a nanoparticle comprising a matrix, a toxic agent, and a cardiac targeting moiety.

25 . The composition of claim 24 , wherein said toxic agent is selected from the group consisting of a photosensitizer, a chemotherapeutic agent, and a sonodynamic agent.

26 . The composition of claim 25 , wherein said photosensitizer is selected from the group consisting of methylene blue, chlorin e6 (Ce6), Photofrin, 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH), coomasie blue, and gold.

27 . The composition of claim 24 , wherein said cardiac targeting moiety is cardiac targeting peptide.

28 . The composition of claim 27 , wherein said cardiac targeting peptide has the amino acid sequence of SEQ ID NO:1.

29 - 31 . (canceled)

32 . A system, comprising:
a) a nanoparticle comprising a matrix, a toxic agent, and a cardiac targeting moiety; and b) an instrument for delivery of an activator of said toxic agent.

33 . The system of claim 32 , wherein said toxic agent is selected from the group consisting of a photosensitizer, a chemotherapeutic agent, and a sonodynamic agent.

34 . The system of claim 33 , wherein said photosensitizer is selected from the group consisting of methylene blue, Ce6, coomasie blue, and gold.

35 . The system of claim 32 , wherein said cardiac targeting moiety is cardiac targeting peptide.

36 . The system of claim 35 , wherein said cardiac targeting peptide has the amino acid sequence of SEQ ID NO:1.

37 . The system of claim 32 , wherein said instrument is selected from the group consisting of a laser and an ultrasound instrument.

38 . The system of claim 32 , further comprising an imaging component.

39 - 41 . (canceled)

42 . A cell selective therapy for treating atrial fibrillation through the method of selective ablation of cardiomyocytes, the method comprising:
a) contacting an animal with a nanoparticle comprising a polymeric matrix, a photosensitizer, and a cardiac targeting moiety; wherein the cardiac targeting moiety is specific to cardiomyocytes; b) illuminating a cardiac tissue of the animal with light, thereby providing an illuminated cardiac tissue comprising illuminated cardiomyocytes and illuminated other cardiac tissue; c) whereby the light activates the photosensitizer; and, d) wherein the activation results in a selective ablation of the cardiomyocytes in the illuminated cardiac tissue, while not ablating the other illuminated cardiac tissue.

43 . The method of claim 42 , wherein the nanoparticle polymeric matrix is selected from the group of consisting of polyethylenglycol and polyacrylamide.

44 . The method of claim 43 , wherein the nanoparticle matrix consists essentially of polyethylglycol.

45 . The method of claim 43 , wherein the nanoparticle is 8-arm PEG.

46 . The method of claim 42 , wherein the light is a laser beam.

47 . The method of claim 42 , where the light comprises light having a wavelength of 647 nm.

48 . The method of claim 47 , wherein the light comprises light having a wavelength of 671 nm.

49 . The methods of claim 42 , wherein the animal is a human.

Assignees

• Univ Michigan Regents

Inventors

• Kalifa Jerome
• Kopelman Raoul
• Avula Uma Mahesh R
• Kim Gwangseong
• Lee Yong-Eun Koo
• Yoon Hyung Ki

Classifications

• A61K33/243 Primary

  Platinum; Compounds thereof · CPC title

• A61K9/5138

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K38/21

  Interferons {[IFN]} · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K31/5415

  ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam · CPC title