# US 8,147,802 B2 · Chelator-functionalized nanoparticles

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- Number: US 8,147,802 B2
- Document ID: US8147802B2
- Status: Granted
- Kind: B2
- Application number: 11/864,453
- Filed: 2007-09-28
- Published: 2009-04-02
- Granted: 2012-04-03
- Earliest claimed: 2007-09-28
- Assignees: General Electric Company
- Inventors: Zhebo Ding; Brian James Grimmond; Michael Luttrell; Slawomir Rubinsztajn; David Cheney deMoulpied; Margaret L. Blohm
- Web page: https://patentgrep.com/patent/US8147802B2

## CPC

- A61K 49/1881: {wherein the coating consists of chelates, i.e. chelating group complexing a (super)(para)magnetic ion, bound to the surface}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- 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)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Provided herein are chelator-functionalized nanoparticles comprising a passive core; and an active coating that demonstrate T1 magnetic resonance pattern upon exposure to a magnetic field. Also provided are methods of making such chelator-functionalized nanoparticles as well as imaging methods using the nanoparticles.

## Claims

### Claim 1

A nanoparticle comprising:
an MR-passive core having a coating comprising functionalized organosilane moieties and a plurality of linear chelators, wherein each of the plurality of linear chelators is attached to the passive core via an organosilane moiety through a single point of attachment; and
a plurality of non-paramagnetic counterions, wherein each of the plurality of non-paramagnetic counterions is complexed with the linear chelator; and wherein the DH of the nanoparticle is less than 35 nm.

### Claim 2 (depends on 1)

The nanoparticle of claim 1, wherein the linear chelator selected from ethylenediamine tetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), or Triethylenetetraminehexacetic acid (TTHA), N-tris(2-aminoethyl)amine-N′,N′,N″,N″,N′″,N′″-hexaacetate (TTAHA) or combinations thereof.

### Claim 3 (depends on 1)

The nanoparticle of claim 1, wherein the passive core comprises an inorganic material selected from silicon, aluminum, titanium, germanium, or derivatives thereof.

### Claim 4 (depends on 3)

The nanoparticle of claim 3, wherein the passive core comprises silica.

### Claim 5 (depends on 1)

The nanoparticle of claim 1, wherein the non-paramagnetic counterions are selected from sodium, triethylammonium, potassium, calcium, dimegulamine, protons, or combinations thereof.

### Claim 6 (depends on 1)

The nanoparticle of claim 1, wherein the non-paramagnetic counterions are substituted with paramagnetic ions selected from Gd, Fe, Mn, or combinations thereof.

### Claim 7 (depends on 6)

The nanoparticle of claim 6, wherein the surface density of paramagnetic ions complexed with the linear chelator is between 0.2 to 6 complexed paramagnetic ions per square nanometer.

### Claim 8 (depends on 6)

The nanoparticle of claim 6, wherein an r2/r1 ratio of the nanoparticle is greater than 1 and less than 2.5.

### Claim 9 (depends on 1)

The nanoparticle of claim 1, wherein the organosilane moiety is selected from N-(trimethoxysilylpropyl)ethylene diamine triacetic acid trisodium salt, N-(trimethoxysilylpropyl)-O-polyethylene oxide urethane, N-(trimethoxysilyl)propyl succinic anhydride, N-(trihydroxysilyl)propylmethylphosphonate, sodium salt, 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, 3-aminopropyltriethoxysilane, or combinations thereof.

### Claim 10 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle further comprises a pharmacokinetic modifier selected from PEG, dextran, alkyl chain, ethylene glycol, poly L,L-lactic acid (PLLA), poly-caprolactone (PCL), 3-(trihydroxysilyl)-propylmethylphosphonate (THPMP), poly(2-methyl-2-oxazolidinone), poly(2-ethyl-2-oxazolidinone), poly(vinylpyrrolidinone), poly(arylamides), phosphonates, or combinations thereof.