IP Library Granted Patent US 10,561,745
Granted Patent B2
US 10,561,745 · App. 15/471,719 · Granted Feb 18, 2020

Stimuli-responsive magneto-plasmonic nanocarrier

Inventors: Asahi Tomitaka (Miami, FL); Madhavan Nair (Coral Gables, FL)
Assignee: THE FLORIDA INTERNATIONAL UNIVERSITY BOARD OF TRUSTEES
A61K49/0002A61K9/127A61K41/00A61K47/6923A61K47/6929A61K49/0065A61K49/0093A61K49/0423A61K49/183A61K9/0019
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Quick Facts
Patent No.
US 10,561,745
App. No.
15/471,719
Granted
Feb 18, 2020
Kind
B2
Abstract

Materials and methods for synthesizing magnetic core/gold shell nanoparticles and magneto-plasmonic nanostars are provided. Formulations comprising nanoparticles optionally bound to or co-loaded with a therapeutic agent encapsulated within liposomes are provided. A method for treating diseases (e.g., brain diseases) in a subject by administering to the subject a formulation comprising the nanoparticle formulation is also provided. Further, a method is provided for imaging a target site of a subject following the administering of the nanoparticle formulations.

Claims (39)

1. Magneto-plasmonic nanostars, having a magnetic core of iron oxide and a gold shell, synthesized by a method comprising the steps of:

a) contacting iron oxide nanoparticles with an acid and, optionally, sonicating the resultant mixture the iron oxide core having a hydrodynamic size between 49 nm and 77 nm;

b) adding a reducing agent to the mixture produced in step a) to coat iron oxide nanoparticles with the reducing agent and optionally, sonicating the resultant mixture;

c) washing and separating the coated iron oxide nanoparticles from the mixture produced in step b);

d) dispersing and sonicating the coated iron oxide nanoparticles produced in step c) in a solution of reducing agent and heating the resulting mixture to boiling temperature, optionally, with stirring;

e) adding a gold precursor to the mixture produced in step d) to produce magnetic core/gold shell nanoparticles (MNP@Au) with the magnetic core being the coated iron oxide nanoparticles, and MNP@Au having a hydrodynamic size of 51 nm to 220 nm, the MNP@Au having an average shell thickness of 2.3 nm;

f) dispersing the MNP@Au in a solution consisting of HAuCl 4 aqueous solution;

g) adding silver nitrate to the solution of step f);

h) adding an acid to the mixture of step g); and

i) neutralizing the solution of step h) with a base;

said nanostars having a single surface plasmon resonance (SPR) peak being about 700 nm to about 750 nm, and said nanostars are bound to a therapeutic agent, the agent being capable of being released from the nanostars by applying a near-infrared light source.

2. A method of treating a disease in a subject, the method comprising the steps of:

i) administering to the subject a formulation comprising magneto-plasmonic nanostars of claim 1 ; and

ii) applying an alternating current magnetic field to the subject to induce local electric charge oscillations in the MNP@Au to release the therapeutic agent.

3. The method of claim 2 , wherein the nanostars are capable of releasing the MNP@Au and the therapeutic agent when subjected to changes in one or more of the following stimuli: alternating current magnetic field, near-infrared light, pH, and temperature.

4. A method of visualizing a target site in a subject, the method comprising the steps of:

i) administering to the subject magneto-plasmonic nanostars of claim 1 ; and

ii) visualizing the target site by applying to the target site one or more of the following: magnetic field, X-rays, and non-ionizing radiation.

5. The magneto-plasmonic nanostars of claim 1 , wherein the acid of step a) is selected from hydrochloric acid, acetic acid, and sulfuric acid.

6. The magneto-plasmonic nanostars of claim 1 , wherein the reducing agent is selected from sodium citrate, ascorbic acid, sodium borohydride, and polyvinyl pyrrolidine.

7. The magneto-plasmonic nanostars of claim 1 , wherein the gold precursor is selected from HAuCl 4 , AuCl 3 , and Au(OH) 3 .

8. The magneto-plasmonic nanostars of claim 1 , wherein in step d) the reducing agent is used at a concentration between 0.5 mM and 20 mM and in step e) the gold precursor is used at a concentration between 1.5 μM and 15 μM.

9. The magneto-plasmonic nanostars of claim 1 , the method further comprising isolating MNP@Au produced at the end of step e) by administering a magnetic field and washing the isolated MNP@Au.

10. The magneto-plasmonic nanostars of claim 1 , the method further comprising binding the nanostars to a therapeutic agent via one or more of the following molecular interactions: ionic bond, electrostatic attraction, gold-sulfur bond, and metal-phosphate bond.

11. The magneto-plasmonic nanostars of claim 1 , the method further comprising encapsulating the nanostars bound to the therapeutic agent within liposomes, wherein the liposomes comprise lipids and optionally cholesterol.

12. The magneto-plasmonic nanostars of claim 1 , the method further comprising modifying the nanostars with a coating comprising thiol molecules.

13. The magneto-plasmonic nanostars of claim 12 , wherein the coating comprises one or more of the following: PEG-SH, HS-PEG-COOH, HS-PEG-NH 2 , 11-Mercaptoundecanoic acid, and peptides comprising thiol molecules.

14. A magnetic core/gold shell nanoparticle, comprising

an iron oxide core having a hydrodynamic size between 49 nm and 77 nm;

a shell covering the iron oxide core,

in which the shell comprises gold; and

a therapeutic agent bonded to the shell,

in which the magnetic core/gold shell nanoparticle is a nanostar having a single SPR peak being about 700 nm to about 750 nm, and the therapeutic agent is capable of being released from the nanostars by applying a near-infrared light source; and

the nanostars bound to the therapeutic agent being encapsulated within liposomes, the liposomes comprising lipids and cholesterol, the therapeutic agent to lipid ratio being from 0.1:34 to 1:34.

15. The magnetic core/gold shell nanoparticle of claim 14 , in which the nanoparticle is coated with thiol PEG, PEG-SH, HS-PEG-COOH, HS-PEG-NH 2 , 11-Mercaptoundecanoic acid, or thiol-containing peptides.

16. The magneto-plasmonic nanostars of claim 1 , in step d) the solution of reducing agent having an acidic pH.

17. The magneto-plasmonic nanostars of claim 16 , the acidic pH being 3.2, 5.5 or 6.

18. The magneto-plasmonic nanostars of claim 11 , the nanostars bound to the therapeutic agent within liposomes having a therapeutic agent to lipid ratio from 0.1:34 to 1:34.

19. The magneto-plasmonic nanostars of claim 1 , step h) having a reaction time of 1 min.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 13, 2017
From: TOMITAKA, ASAHI; NAIR, MADHAVAN
To: THE FLORIDA INTERNATIONAL UNIVERSITY BOARD OF TRUSTEES
Reel/Frame 042001/0352 →
Continuity (1)
Related Publication 20180280546A1 · Oct 4, 2018
Cited By (1)
US 12,692,398