# US 8,771,741 B2 · In vivo photodynamic therapy of cancer via a near infrared agent encapsulated in calcium phosphate nanoparticles

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- Number: US 8,771,741 B2
- Document ID: US8771741B2
- Status: Granted
- Kind: B2
- Application number: 12/657,556
- Filed: 2010-01-22
- Published: 2010-09-30
- Granted: 2014-07-08
- Earliest claimed: 2009-01-23
- Assignees: The Penn State Research Foundation
- Applicants: James H. Adair; Mark Kester; Erhan I. Altinoglu; Brian M. Barth; Timothy J. Russin; James M. D. Kaiser; Thomas T. Morgan; Karen L. Eklund
- Inventors: James H. Adair; Mark Kester; Peter C. Eklund; Erhan I. Altinoglu; Brian M. Barth; Timothy J. Russin; James M. D. Kaiser; Thomas T. Morgan
- Web page: https://patentgrep.com/patent/US8771741B2

## CPC

- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- A61K 47/6921: {the form being a particulate, a powder, an adsorbate, a bead or a sphere}
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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

Nano-encapsulated photosensitizers and their use in the treatment of tumors and/or imaging is described. Preferably, the photosensitizers are encapsulated in a calcium phosphate nanoparticle (CPNP). Encapsulating the PS in a CPNP increases the half-life of the PS, increases absorption of the PS into the target cell tissue, increases the photostability of the PS, increases the photoefficiency of the PS, increases in vivo retention of the PS, or combinations thereof, ultimately making it a highly efficacious agent for use in photodynamic therapy, imaging target tissues, vessels, or tumors, and/or detecting or locating tumors.

## Claims

### Claim 1

A method of treating tumors or imaging targeted tissue in a subject, comprising:
administering to the subject in need thereof an effective amount of a photosensitizer (PS) encapsulated in a calcium phosphate nanoparticle (CPNP); and
exposing the tumor or tissue of the subject to a photo-activating amount of light at a wavelength that activates the PS for a sufficient amount of time to obtain a desired response.

### Claim 2 (depends on 1)

The method of claim 1 wherein the PS is a near-infrared PS.

### Claim 3 (depends on 1)

The method of claim 1 wherein the photosensitizer comprises indocyanine green, Cy3 Amidite, Cascade Blue©, 10-(3-Sulfopropyl)acridinium betaine (SAB), a fluorescein sodium salt, rhodamine WT, a coumarin or a porphyrin.

### Claim 4 (depends on 1)

The method of claim 1 wherein the nanoparticle comprises on its surface a carboxylate, PEG, or amine functional group.

### Claim 5 (depends on 1)

The method of claim 1 wherein the nanoparticle comprises on its surface a targeting moiety.

### Claim 6 (depends on 5)

The method of claim 5 wherein the targeting moiety comprises a ligand or an antibody.

### Claim 7 (depends on 1)

The method according to claim 1 wherein the nanoencapsulated near-infrared photosensitizer is administered topically, intravenously, orally, locally, subcutaneously, intramuscularly, or intraperitoneally.

### Claim 8 (depends on 1)

The method according to claim 1 wherein the PS accumulates in the tumor.

### Claim 9 (depends on 1)

The method according to claim 1 wherein the subject is a mammal.

### Claim 10 (depends on 1)

The method according to claim 1 wherein the subject is a human.

### Claim 11 (depends on 1)

The method according to claim 1 wherein the desired response is inhibition of tumor growth.

### Claim 12 (depends on 1)

The method according to claim 1 wherein the desired response is a protective response against tumor challenge in the subject.

### Claim 13 (depends on 1)

The method according to claim 1 wherein the desired response is eradication of distant tumors or metastasized tumors not directly targeted with the photosensitizer (PS) encapsulated in the CPNP.

### Claim 14 (depends on 1)

The method according to claim 1 wherein the tumor is a solid tumor.

### Claim 15 (depends on 1)

The method according to claim 1 wherein the subject is suffering from leukemia or a lymphoma.

### Claim 16 (depends on 1)

The method according to claim 1 wherein the desired response is the production of an increased amount of reactive oxygen species by the nano-encapsulated PS as compared to an amount of reactive oxygen species produced by a control wherein the PS is not nano-encapsulated.

### Claim 17 (depends on 1)

The method according to claim 1 wherein the desired response is the production of an increased amount of endogenous pro-apoptotic lipids by the nano-encapsulated PS as compared to an amount of endogenous pro-apoptotic produced by a control wherein the photosensitizer is not nano-encapsulated.

### Claim 18 (depends on 17)

The method according to claim 17 wherein the endogenous pro-apoptotic lipids comprise ceramide, dihydroceramide or combinations thereof.

### Claim 19 (depends on 1)

The method according to claim 1 wherein the radiation comprises light, ultrasound, magnetic force, electromagnetic radiation in the ultra violet or visible electromagnetic spectrum or near infrared.

### Claim 20 (depends on 1)

The method according to claim 1 further comprising imaging the tumor or target tissue using an effective amount of the encapsulated PS to obtain imaging data of the tumor or target tissue.

### Claim 21 (depends on 20)

The method according to claim 20 further comprising analyzing the imaging data to quantify a dosing schedule for the PS encapsulated in the CPNP photodynamic treatment of the tumor.

### Claim 22 (depends on 20)

The method according to claim 20 comprising imaging the target tissue or tumor prior to, concomitant with, or subsequent to treating the tumor or tissue with the encapsulated PS.

### Claim 23 (depends on 20)

The method according to claim 20 further comprising imaging deep target tissue or tumor cells.

### Claim 24 (depends on 23)

The method according to claim 23 further comprising imaging deep target tissue or tumor cells at a depth of about 3 cm to about 10 cm.

### Claim 25 (depends on 1)

The method according to claim 1 wherein the CPNP further comprises an agent for the treatment of cancer.

### Claim 26 (depends on 1)

The method according to claim 1 wherein the PS is used to image vessels to obtain data for determining atherosclerosis, restenosis or graft disease.
