Small Highly Uniform Nanomedicine Compositions for Therapeutic, Imaging and Theranostic Applications

Patent metadata

Field	Value
Publication number	US-2020101176-A1
Application number	US-201916570784-A
Country	US
Kind code	A1
Filing date	Sep 13, 2019
Priority date	Sep 13, 2018
Publication date	Apr 2, 2020
Grant date	—

Abstract

A targetable nanoconstruct capable of simultaneously serving as a therapeutic platform for photodynamic therapy as well as an MR molecular imaging agent, free of heavy metal atoms. F3-cys targeting agent nanoconstructs, including 8PEGA-Ce6 NCs. A label-free 8PEGA nanoconstruct that can be directly and selectively imaged by MRI, using standard spin-echo imaging sequences with large diffusion magnetic field gradients to suppress the water signal.

First claim

1 . A composition having therapy, imaging, diagnostic or theranostic applications, the composition comprising:
a plurality of nanoparticles, wherein the nanoparticles comprise a backbone material; an active agent attached to the backbone; and, wherein, the plurality of nanoparticles has a predetermined particle size distribution defined by a D10=n−5, D50=n, D90=x+5.

2 . The composition of claim 1 , wherein n is a number in the range of about 5 nm to about 25 nm.

3 . The composition of claim 1 , wherein n is a number in the range of 7 nm to 22 nm.

4 . The composition of claim 1 , wherein n is a number in the range of about 10 nm to about 20 nm.

5 .- 54 . (canceled)

55 . A method of providing a PDT, the method comprising:
obtaining data from an MRI of nanoparticles in a subject; and, using the data, at least in part, to provide a PDT; wherein the nanoparticles are essential free from heavy metals.

56 . The method of claim 55 , wherein the nanoparticles have less than 1 ppm heavy metals.

57 . The method of claim 55 , wherein the nanoparticles have less than 0.1 ppm heavy metals.

58 . The method of claim 55 , wherein the nanoparticles have less than 0.01 ppm heavy metals.

59 . The method of claim 55 , wherein the nanoparticles have less than 0.001 ppm heavy metals.

60 . A method of providing a PDT, the method comprising:
obtaining data from an MRI of nanoparticles in a subject; and, using the data, at least in part, to provide a PDT; wherein the nanoparticles are essential free from gadolinium.

61 .- 64 . (canceled)

65 . A method of obtaining data for use in guiding therapeutic applications, the method comprising:
administering an imaging agent comprising a plurality of nanoparticles to a subject; the nanoparticles being essentially from gadolinium; and, performing a nuclear magnetic resonance scan of the subject after administration of the imaging agent; wherein the nanoparticles are directly imaged; thereby providing an MRI of the nanoparticles and data related to the nanoparticles and the subject.

66 . The method of claim 65 , wherein the nanoparticles have less than 1 ppm gadolinium.

67 . The method of claim 66 , wherein the nanoparticles have less than 0.1 ppm gadolinium.

68 .- 86 . (canceled)

87 . A nuclear magnetic resonance imaging agent, the imaging agent comprising:
a plurality of nanoparticles that are essentially free from heavy metals; the nanoparticles comprising PEG; wherein the nanoparticles are capable of being directly imaged by a magnetic field generated by a magnetic resonance imaging system.

88 .- 90 . (canceled)

91 . An imaging agent comprising nanoparticles that are capable of being directly imaged by the magnetic field in a magnetic resonance imaging device, the nanoparticles comprising:
a nanoconstruct comprising a backbone material, wherein the backbone material is non-paramagnetic; and, the nanoconstruct is capable of being directly imaged by a magnetic field.

92 . The imaging agent of claim 91 , wherein the nanoconstruct comprises about 2,000 to about 5,000 protons; and, wherein the nanoconstruct is less than 25 nm.

93 . The imaging agent of claim 91 , wherein the nanoconstruct comprises about 3,600 protons; and, wherein the nanoconstruct is less than 25 nm.

94 . The imaging agent of claim 91 , wherein the nanoconstruct comprises about 3,000 to about 5,000 protons; and, wherein the nanoconstruct is less than 20 nm.

95 . The imaging agent of claim 91 , wherein the nanoconstruct comprises about 5,000 to about 15,000 protons; and, wherein the nanoconstruct is less than 50 nm.

96 .- 102 . (canceled)

103 . An MRI system, the system configured to generate three magnetic fields; a first, a strong static magnetic field to create energy level differences in nuclei with spin angular momentum and gives rise to bulk nuclear magnetization; a second, a radio frequency field is used to tip the created nuclear magnetization so that it can be detected by RF coils; a third set of magnetic field gradients is used to spatially encode the signal to create a map of nuclear magnetization; the magnetic fields configured to generate an image of non-water protons present in an additive placed in a subject to be imaged; wherein the magnetic field gradients can be pulsed in a specific manner to sensitize the nuclei to motion due to flow or diffusion.

104 . A method of imaging an 8PEGA imaging agent, the method comprising: providing a diffusion weighted spin-echo imaging sequence having a repetition time TR=500 ms, an echo time TE=200 ms, a pair of diffusion encoding gradients with amplitude G diff =126 mT/m, duration δ=7.1 ms, and separation ∇=180 ms to generate a diffusion b value of 10 10 s/m 2 .

105 . The method of claim 104 , wherein the magnetic field gradients attenuate the MR signal intensity by S(b)=exp(−bD) where

b
=

(

γ



δ




G
diff

)

2



(

Δ
-

δ
3

)

.

106 .- 107 . (canceled)

108 . A method of obtaining an MRI image of a subject, the method comprising: administering an imaging agent to a subject; and obtaining an MRI image of the subject; wherein the MRI image comprising a direct image of non-water based protons contained in in the imaging agent.

109 . (canceled)

Assignees

• Univ Michigan Regents

Inventors

• Hopkins Thomas
• Swanson Scott D
• Kopelman Raoul

Classifications

• A61B5/055

  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging · CPC title

• B82Y30/00

  Nanotechnology for materials or surface science, e.g. nanocomposites · CPC title

• A61N5/062 Primary

  Photodynamic therapy, i.e. excitation of an agent · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• B82Y15/00

  Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors · CPC title