Targeted nanoparticle conjugates

Patent metadata

Field	Value
Publication number	US-10363309-B2
Application number	US-201213983750-A
Country	US
Kind code	B2
Filing date	Feb 5, 2012
Priority date	Feb 4, 2011
Publication date	Jul 30, 2019
Grant date	Jul 30, 2019

Abstract

A composition for treating a disorder in a subject includes a polyethylene glycolylated (PEGylated) nanoparticle, at least one hydrophobic therapeutic agent coupled to the surface of the nanoparticle; and at least one targeting moiety coupled to polyethylene glycol of the nanoparticle for targeting the composition to a cell associated with disorder.

First claim

Having described the invention, the following is claimed:

1. A composition for treating a disorder in a subject, the composition comprising:
a polyethylene glycolylated (PEGylated) nanoparticle;
at least one hydrophobic therapeutic agent non-covalently coupled to the surface of the nanoparticle, wherein the at least one hydrophobic therapeutic agent has an amino or amine functionality for attachment to the surface of the nanoparticle; and
at least one targeting moiety coupled to polyethylene glycol of the nanoparticle for targeting the composition to a cell associated with the disorder, wherein the at least one therapeutic agent is released from the nanoparticle and differentially up taken by the cell upon targeting with reduced nanoparticle accumulation in the cell.

2. The composition of claim 1 , wherein the disorder is cancer and the at least one targeting moiety targets the composition to a cancer cell.

3. The composition of claim 2 , wherein the at least one hydrophobic therapeutic agent is an anti-cancer agent.

4. The composition of claim 3 , wherein the anti-cancer agent comprises Phthalocyanine 4.

5. The composition of claim 2 , wherein the at least one targeting moiety comprises a polypeptide that binds to epidermal growth factor receptor (EGFR).

6. The composition of claim 5 , wherein the polypeptide comprises an epidermal growth factor (EGF) peptide having the amino acid sequence of SEQ ID NO: 1.

7. A composition for treating cancer in a subject, the composition comprising:
a polyethylene glycolylated (PEGylated) gold nanoparticle;
at least one hydrophobic anti-cancer agent non-covalently coupled to the surface of the gold nanoparticle, wherein the at least one hydrophobic anti-cancer agent has an amino or amine functionality for attachment to the surface of the nanoparticle; and
at least one targeting moiety coupled to polyethylene glycol of the nanoparticle for targeting the composition to a cancer cell, wherein the at least one anti-cancer agent is released from the nanoparticle and differentially up taken by a cancer cell upon targeting with reduced nanoparticle accumulation in the cell.

8. The composition of claim 7 , wherein the at least one anti-cancer agent comprises Phthalocyanine 4.

9. The composition of claim 7 , wherein the at least one targeting moiety comprises a polypeptide that binds to epidermal growth factor receptor (EGFR).

10. The composition of claim 9 , wherein the polypeptide comprises an epidermal growth factor (EGF) peptide having the amino acid sequence of SEQ ID NO: 1.

11. A composition for treating brain cancer, the composition comprising:
a polyethylene glycolylated (PEGylated) gold nanoparticle;
Phthalocyanine 4 non-covalently conjugated to the PEGylated gold nanoparticle; and
a polypeptide coupled to polyethylene glycol of the nanoparticle, the polypeptide binding epidermal growth factor receptor (EGFR), wherein the Phthalocyanine 4 is released from the nanoparticle and differentially up taken by brain cancer cells upon targeting with reduced nanoparticle accumulation in the cell.

12. The composition of claim 11 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 1.

13. The composition of claim 11 , wherein the composition upon systemic administration to the subject crosses the blood brain barrier and targets the brain cancer cells.

14. The composition of claim 13 , wherein the Phthalocyanine 4 upon uptake is activated by light to cause the cancer death or suppress the cancer growth.

15. The composition of claim 1 , wherein the at least one hydrophobic therapeutic agent is selected from the group consisting of Phthalocyanine 4, 5-aminolevulinic acid, rosiglitazone, and pioglitazone.

16. The composition of claim 7 , wherein the at least one hydrophobic anti-cancer agent is selected from the group consisting of Phthalocyanine 4, 5-aminolevulinic acid, rosiglitazone, and pioglitazone.

Assignees

• Basilion James
• Burda Clemens
• Univ Case Western Reserve

Inventors

• Basilion James
• Burda Clemens

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K41/0071 Primary

  PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines · CPC title

• A61K47/6935

  the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol · CPC title

• A61K47/6923

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title