Nanotubes as mitochondrial uncouplers

• US 8,357,845 B2
• Filed: 02/25/2011
• Issued: 01/22/2013
• Est. Priority Date: 05/06/2005
• Status: Active Grant

• Current Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Original Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Inventors: Sullivan, Patrick G.
• Primary Examiner(s): Ford, Allison
• Assistant Examiner(s): FERNANDEZ, SUSAN EMILY
• Application Number:
  US13/035,649
• Publication Number:
  US 20110160694A1
• Time in Patent Office: 697 Days
• Field of Search: None
• US Class Current: 977/915
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/717 Celluloses
• CPC Class Codes: A61K 31/718 Starch or degraded starch, e.g. amylose, amylopectin
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/242 Gold; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61K 33/44 Elemental carbon, e.g. charcoal, carbon black
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/1274 Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 977/734 : Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
• CPC Class Codes: Y10S 977/773 : Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/788 : Of specified organic or carbon-based composition
• CPC Class Codes: Y10S 977/81 : Of specified metal or metal alloy composition
• CPC Class Codes: Y10S 977/902 : Specified use of nanostructure
• CPC Class Codes: Y10S 977/904 : for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/915 : Therapeutic or pharmaceutical composition

Abstract

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Claims

1. A method of reducing weight in an individual comprising:

administering a therapeutically effective amount of nanotubes into the individual, wherein the nanotubes are self-rectifying metal nanotubes, having a length of less than 50 nm and a conductance such that the nanotubes conduct protons only when a proton gradient of about 120-220 mV is present.

2. The method of claim 1, wherein the individual is a mammal.

3. The method of claim 1, wherein the nanotubes have an inner diameter designed for uncoupling mitochondria.

4. The method of claim 1, wherein the self-rectifying metal nanotubes comprise at least one of gold and silver.