Metal bisphosphonate nanoparticles for anti-cancer therapy and imaging and for treating bone disorders

Patent metadata

Field	Value
Publication number	US-9693957-B2
Application number	US-201214131575-A
Country	US
Kind code	B2
Filing date	Jul 9, 2012
Priority date	Jul 8, 2011
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

Metal-bisphosphonate nanoparticles are disclosed. Also disclosed are pharmaceutical compositions including the metal-bisphosphonate nanoparticles, methods of preparing the metal-bisphosphonate nanoparticles and materials comprising the nanoparticles, and methods of using the compositions to treat cancer or bone-related disorders (e.g., bone-resorption-related diseases, osteoporosis, Paget's disease, and bone metastases) and as imaging agents.

First claim

What is claimed is:

1. A metal-bisphosphonate nanoparticle comprising a core comprising a coordination complex between:
(a) M 1 , wherein M 1 is a multivalent metal ion; and
(b) a bisphosphonate, wherein the bisphosphonate comprises a metal complex having the formula M 2 L x-2 [O—C(═O)—NH—P(═O)(OR) 2 ] 2 , wherein x is an integer of 2 or greater, M 2 is a platinum ion, each L is a monodentate or bidentate ligand, and wherein each R is independently H, alkyl, substituted alkyl, aralkyl, aryl, substituted aryl, or a negative charge.

2. The metal-bisphosphonate nanoparticle of claim 1 , wherein each R is independently H, alkyl, or a negative charge.

3. The metal-bisphosphonate nanoparticle of claim 1 , wherein the nanoparticle further comprises one or more coating agents or layers surrounding at least a portion of an outer surface of the core.

4. The metal bisphosphonate nanoparticle of claim 3 , wherein the one or more coating agents or layers comprise at least one lipid coating layer or agent.

5. The metal-bisphosphonate nanoparticle of claim 1 , further comprising a non-bisphosphonate therapeutic agent or prodrug thereof and/or an imaging agent.

6. A pharmaceutical composition comprising a metal-bisphosphonate nanoparticle of claim 1 ; and a pharmaceutically acceptable carrier.

7. A method of treating a cancer or a bone related disorder selected from the group consisting of osteoporosis and Paget's disease in a subject in need of treatment thereof, wherein the method comprises administering to the subject an effective amount of a metal-bisphosphonate nanoparticle of claim 1 .

8. The metal-bisphosphonate nanoparticle of claim 5 , wherein the non-bisphosphonate therapeutic agent is a small interfering RNA.

9. The metal-bisphosphonate nanoparticle of claim 1 , wherein M 1 is Zn 2+ .

10. The metal-bisphosphonate nanoparticle of claim 1 , wherein x is 5 or 6 and wherein each L is independently selected from the group consisting of CI, Br, F, I, NH 3 , alkylamino, alkoxy, hydroxyl, diol, and diamine.

11. The metal-bisphosphonate nanoparticle of claim 1 , wherein M 1 is Zn 2+ , x is 6, each L is selected from halo and NH 3 , and wherein each R is H, alkyl or a negative charge.

Assignees

• Lin Wenbin
• Liu Demin
• Della Rocca Joseph
• Kramer Stephanie A
• Poon Christopher Y
• Univ North Carolina Chapel Hill

Inventors

• Lin Wenbin
• Liu Demin
• Della Rocca Joseph
• Kramer Stephanie A
• Poon Christopher Y

Classifications

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6929

  the form being a nanoparticle, e.g. an immuno-nanoparticle · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title