Targeted nanoparticle conjugates

Patent metadata

Field	Value
Publication number	US-10905762-B2
Application number	US-201916526687-A
Country	US
Kind code	B2
Filing date	Jul 30, 2019
Priority date	Feb 4, 2011
Publication date	Feb 2, 2021
Grant date	Feb 2, 2021

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 method for treating cancer in a subject in need thereof, the method comprising:
administering to the subject with cancer a therapeutically effective amount of a composition comprising:
a polyethylene glycolylated nanoparticle;
at least one hydrophobic anti-cancer agent non-covalently coupled to the surface of the 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 the cancer cell upon targeting with reduced nanoparticle accumulation in the cancer cell.

2. The method of claim 1 , wherein the anti-cancer agent comprises Phthalocyanine 4.

3. The method of claim 2 , further comprising exposing the cancer cell to laser light, thereby inducing cytoxic effects of Phthalocyanine 4 up taken by the cancer cell.

4. The method of claim 1 , wherein the at least one targeting moiety comprises a polypeptide that binds to an epidermal growth factor receptor (EGFR).

5. The method of claim 4 , wherein the polypeptide comprises an epidermal growth factor (EGF) peptide having the amino acid sequence of SEQ ID NO: 1.

6. A method of treating brain cancer in a subject in need thereof, the method comprising:
administering parenterally to the subject with brain cancer a therapeutically effective amount of a composition comprising:
a polyethylene glycolylated nanoparticle;
at least one hydrophobic anti-cancer agent non-covalently coupled to the surface of the 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 brain cancer cell, wherein the at least one anti-cancer agent is released from the nanoparticle and differentially up taken by brain cancer cells upon targeting with reduced nanoparticle accumulation in the brain cancer cells.

7. The method of claim 6 , wherein the composition upon parenteral administration to the subject crosses the blood brain barrier and targets the brain cancer cells.

8. The method of claim 6 , wherein the anti-cancer agent comprises Phthalocyanine 4.

9. The method of claim 8 , further comprising exposing the brain cancer cell to light, thereby inducing cytoxic effects of Phthalocyanine 4 up taken by the brain cancer cell.

10. The method of claim 6 , wherein the at least one targeting moiety comprises a polypeptide that binds to an epidermal growth factor receptor (EGFR).

11. The method of claim 10 , wherein the polypeptide comprises an (EGF) having the amino acid sequence of SEQ ID NO: 1.

12. The method of claim 6 , wherein the composition is administered by intravenous injection.

13. A method for treating brain cancer in a subject in need thereof, the method comprising:
(a) administering parenterally to the subject with brain cancer a therapeutically effective amount of a composition comprising:
a polyethylene coated gold nanoparticle;
Phthalocyanine 4 non-covalently coupled to the surface of the nanoparticle, wherein the Phthalocyanine 4 is attached to the surface of the nanoparticle through electrostatic interactions; and
an EGF peptide consisting of amino acid sequence YHWYGYTPQNVI, wherein Phthalocyanine 4 is released from the nanoparticle and differentially up taken by the brain cancer cell with reduced nanoparticle accumulation in brain cancer cells; and
(b) exposing the brain cancer cell to laser light, thereby inducing cytoxic effects of Phthalocyanine 4 up taken by the brain cancer cells.

Assignees

• Univ Case Western Reserve

Inventors

• Basilion James
• Burda Clemens

Classifications

• A61K47/6923

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

• 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