IP Library › Granted Patent US 12,329,780
Granted Patent B2
US 12,329,780 · App. 16/608,713 · Granted Jun 17, 2025

Acute and chronic mitochondrial electron transport chain dysfunction treatments and graphenic materials for use thereof

Inventors: James M. Tour (Bellaire, TX); Lizanne Nilewski (La Jolla, CA); William Sikkema (Langley, CA); Kimberly Mendoza (Houston, TX); Thomas Andrew Kent (Houston, TX); William Dalmeida, Jr. (League City, TX); Paul J. Derry (Houston, TX); Ah-Lim Tsai (Sugarland, TX); Muralidhar L. Hegde (Houston, TX); Prakash Dharmalingam (Houston, TX); Pavana Dixit Hegde (Houston, TX); Sankar Mitra (Houston, TX); Joy Mitra (Houston, TX)
Assignees: William Marsh Rice University; Board of Regents, The University of Texas System; Baylor College of Medicine; Houston Methodist Research Institute; The United States Government
A61K33/36A61K9/1641A61K9/51A61K33/04A61K33/24A61K33/241A61K33/26A61K33/30A61K33/34A61P25/28
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Quick Facts
Patent No.
US 12,329,780
App. No.
16/608,713
Granted
Jun 17, 2025
Kind
B2
Abstract

Modified hydrophilic carbon clusters (HCCs), poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs) and similarly structured materials like graphene quantum dots (GQDs), PEGylated GQDs, small molecule antioxidants, and PEGylated small molecule antioxidants. These materials have been modified with an iron chelating moiety, deferoxamine, or a similar chelating moiety. By exploiting common binding sites, the carbon nanostructure facilitates intracellular transport including in mitochondria, reduces oxidative breakdown of the chelator moiety prior to treatment, and reduces both the cause and consequences of metal induced oxidative stress within the body thus providing a novel form of therapy for a range of oxidative and metal-related toxicities. Graphenic materials can be used for the treatment of acute and chronic mitochondrial electron transport chain dysfunction.

Claims (13)

1. A therapeutic composition comprising an antioxidant nanoparticle covalently modified with a chelating moiety, wherein

(a) the antioxidant nanoparticle has both antioxidant and pro-oxidant properties;

(b) the therapeutic composition is operable to act as a high capacity oxidant having an oxygen radical absorbance capacity value between 200 and 15,000 and directly transports electrons and reduces key mitochondrial enzymes when administered to a subject;

(c) the therapeutic composition has a chelation efficacy that is at least ten times greater as compared to a same amount of the chelating moiety without the antioxidant nanoparticle;

(d) the chelating moiety is a metal-chelating moiety; and

(e) the metal-chelating moiety is a chelator of a metal selected from a group consisting of aluminum, americium, arsenic, cadmium, cesium, chromium, copper, curium, iron, lead, mercury, plutonium, thallium, uranium, and zinc, wherein

(i) the chelating moiety is deferoxamine (DEF),

(ii) the antioxidant nanoparticle is selected from a group consisting of poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs), poly(ethylene glycol)-ylated graphene quantum dots (PEG-GQDs), and poly(ethylene glycol)-ylated perylenediimide (PEG-PDI),

(iii) the therapeutic composition is selected from a group consisting of deferoxamine poly(ethylene glycol)-hydrophilic carbon clusters (DEF-PEG-HCCs), deferoxamine poly(ethylene glycol)-ylated graphene quantum dots (DEF-PEG-GQDs), and deferoxamine poly(ethylene glycol)-ylated perylenediimide (DEF-PEG-PDI), and

(iv) ratio of poly(ethylene glycol) (PEG) to chelating moiety is between 1:3 and 3:1.

2. The therapeutic composition of claim 1 , wherein the therapeutic composition has a chelation efficacy that is at least 100 times greater as compared to a same amount of the chelating moiety without the antioxidant nanoparticle.

3. The therapeutic composition of claim 1 , wherein the metal is selected from a group consisting of arsenic, cadmium, copper, iron, lead, zinc, and combinations thereof.

4. The therapeutic composition of claim 1 , wherein the therapeutic composition is operable to treat or reduce mitochondrial injury.

Assignments (7)
CONFIRMATORY LICENSE Recorded Jul 26, 2023
From: RICE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064388/0215 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2023
From: TSAI, AH-LIM
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 063331/0648 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2023
From: HEGDE, MURALIDHAR L.; DHARMALINGAM, PRAKASH; HEGDE, PAVANA DIXIT; MITRA, SANKAR
To: HOUSTON METHODIST RESEARCH INSTITUTE
Reel/Frame 063331/0663 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2023
From: MENDOZA, KIMBERLY
To: WILLIAM MARSH RICE UNIVERSITY
Reel/Frame 063331/0628 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2023
From: KENT, THOMAS ANDREW; DALMEIDA, WILLIAM, JR.; DERRY, PAUL J.
To: BAYLOR COLLEGE OF MEDICINE
Reel/Frame 064103/0155 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2023
From: HEGDE, MURALIDHAR L.; MITRA, JOY
To: HOUSTON METHODIST RESEARCH INSTITUTE
Reel/Frame 063331/0681 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2022
From: TOUR, JAMES M.; NILEWSKI, LIZANNE G.; SIKKEMA, WILLIAM
To: WILLIAM MARSH RICE UNIVERSITY
Reel/Frame 059752/0967 →
Continuity (3)
Provisional Application 62556719 · Sep 11, 2017
Provisional Application 62491995 · Apr 28, 2017
Related Publication 20200222453A1 · Jul 16, 2020
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