METHODS TO REGULATE POLARIZATION AND ENHANCE FUNCTION OF CELLS

• US 20150119794A1
• Filed: 01/07/2015
• Published: 04/30/2015
• Est. Priority Date: 08/05/2005
• Status: Abandoned Application

• Current Assignee: Gholam A. Peyman
• Original Assignee: Gholam A. Peyman
• Inventors: Peyman, Gholam A.
• Application Number:
  US14/591,158
• Publication Number:
  US 20150119794A1
• Time in Patent Office: Days
• US Class Current: 604/21
• CPC Class Codes: A61B 2017/00345 Micromachines, nanomachines, microsystems
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/00727 Apparatus for retinal reattachment
• CPC Class Codes: A61F 9/0079 using non-laser electromagnetic radiation, e.g. non-coherent light or microwaves
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 41/0042 Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0033 the non-active part being non-polymeric
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61K 48/0083 characterised by an aspect of the administration regime
• CPC Class Codes: A61K 49/0067 quantum dots, fluorescent nanocrystals
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/36046 of the eye
• CPC Class Codes: A61N 1/37205 : Microstimulators, e.g. implantable through a cannula
• CPC Class Codes: A61N 2005/063 : comprising light transmitting means, e.g. optical fibres
• CPC Class Codes: A61N 2005/0659 : infrared
• CPC Class Codes: A61N 2005/0661 : ultraviolet
• CPC Class Codes: A61N 2005/0662 : Visible light
• CPC Class Codes: A61N 5/062 : Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61N 5/0622 : Optical stimulation for exciting neural tissue
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Methods and compositions to controllably regulate cells at a target site. A quantum dot-targeting agent complex is administered to a patient in need of therapy, and the complex is stimulated using an implanted fiber optic system. In embodiments, the system includes an electrical sensor that detects and monitors electrical activity of the stimulated controllably regulated cells, and relays this information to a controller that can regulate further stimulation.

Claims

1. A method for delivering an opsin family gene to an anatomical and/or physiological site for stimulating, modifying polarization of, and/or inducing an action potential in a cell at the site, the method comprising

providing a complex comprising a nanoparticle carrier, a biocompatible molecule for cell uptake of the complex, an opsin family gene, a biocompatible fluid, and optionally a targeting moiety and/or a second gene, to the anatomical and/or physiological site, to result in formation of a light activated channel in a cell membrane permitting cell stimulation by an external or internal light transmitted by a fiber optic to modify polarization of, and/or induce an action potential in the cell at the site.

2. The method of claim 1 where the nanoparticle carrier is selected from the group consisting of fullerenes, buckyballs, dendrimers, liposomes, aptamers, and/or micelles.

3. The method of claim 2 where the dendrimer is selected from the group consisting of poly(amidoamine) (PAMAM), poly(amidoamine-organosilicon) (PAMAMOS), poly(propyleneimine) (PPIO), tecto, multilingual, chiral, hybrid, amphiphilic, micellar, multiple antipen peptide, Frechet-type dendrimers, and combinations thereof.

4. The method of claim 1 where the nanoparticle is functionalized to render or enhance biocompatibility.

5. The method of claim 1 where the complex is further treated or delivered to enhance cell penetration.

6. The method of claim 1 where the biocompatible molecule is directly or indirectly associated with, or covalently conjugated to, the nanoparticle carrier and is selected from the group consisting of cell penetrating peptides (CPP), arginine-CPP, cysteine-CPP, polyethylene glycol (PEG), biotin-streptavadin, acetyl cysteine, an antibody, a ligand for a receptor, and combinations thereof.

7. The method of claim 1 where the opsin family gene is selected from the group consisting of rhodopsin, halorhodopsin, photopsin, channelrhodopsin, and combinations thereof.

8. The method of claim 1 wherein the targeting moiety is an antibody or a ligand for a receptor.

9. The method of claim 1 wherein the second gene ameliorates a genetic or acquired degenerative disease or condition.

10. The method of claim 9 where the disease or condition is selected from the group consisting of a degenerative retinal condition, a degenerative central nervous system disease, and a degenerative cardiovascular disease.

11. The method of claim 9 where the second gene encodes a protein or is an inhibitory RNA (RNAi) for gene silencing.

12. The method of claim 1 where the cell is an excitable cell and is selected from the group consisting of a retinal cell, a cardiac cell, a muscle cell, a central nervous system cell (CNS), a spinal cord cell, a peripheral nerve cell, and combinations thereof.

13. The method of claim 1 where the cell is a non-excitable cell and is selected from the group consisting of a fibroblast cell, a glial cell, a stem cell, a pluripotential mesenchymal stem cell, and combinations thereof.

14. The method of claim 1 where the stimulation by light induces cell proliferation.

15. The method of claim 14 where the cell proliferation replaces cell loss at the site.

16. The method of claim 15 where cell loss is from a condition selected from the group consisting of age related macular degeneration, stoke, ischemia, and combinations thereof.

17. The method of claim 1 where providing the complex is by an injection at an intraocular, intravitreal, intraretinal, subretinal, or intrathecal location.

18. The method of claim 1 where the complex delivery to the cell is enhanced by electroporation or mechanical force.

19. The method of claim 1 where the complex is injected in a desired location with an insulated metallic needle connected to a power source to carry electricity into the location tissue for electroporation and delivery of the complex inside the cell.

20. The method of claim 1 further comprising administering a therapeutic agent to the site in association with the complex to ameliorate a condition, the therapeutic agent selected from the group consisting of stem cell therapy, immunomodulators, anti-VEGF agents, anti-integrins, anti-inflammatory agents, antibiotics, anti-viral agents, anti-fungal agents, anti-proliferative agents, and/or anti-cancer agents.