METHODS TO REGULATE POLARIZATION AND ENHANCE FUNCTION OF CELLS

• US 20140336514A1
• Filed: 07/28/2014
• Published: 11/13/2014
• 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:
  US14/444,668
• Publication Number:
  US 20140336514A1
• Time in Patent Office: Days
• US Class Current: 600/473
• CPC Class Codes: A61B 2017/00345 Micromachines, nanomachines, microsystems
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• 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: 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• 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 of providing nanoparticles to a target cell in a patient in need of therapy and/or diagnosis using the nanoparticles, the method comprising

providing to an individual needing therapy and/or diagnosis a complex comprising nanoparticles, a targeting agent to a target cell, and a penetrating agent that enhances or imparts penetration of the complex into the cell,

accumulating the nanoparticles in the target cell, and

applying light to the targeted accumulated nanoparticles in the cell under conditions sufficient to controllably activate the nanoparticles in the target cell to controllably regulate target cell plasma membrane polarization resulting in therapy and/or diagnosis by repolarizing, hyperpolarizing, or hypopolarizing the target cell.

2. The method of claim 1 where the penetrating agent enhances endosomal escape of the complex in the cell.

3. The method of claim 1 where the penetrating agent is directly associated with, indirectly associated with, non-covalently conjugated to, or covalently conjugated to the nanoparticle in the complex.

4. The method of claim 1 where the penetrating agent is selected from the group consisting a micelle, a liposome, a dendrimer, a peptide, a polymer, and combinations thereof.

5. The method of claim 1 where the penetrating agent is a biocompatible or rendered biocompatible polymer, copolymer, or derivative thereof selected from the group consisting of (poly)ethylene glycol (PEG) moieties, poly(ester amide), poly-hydroxyalkanoates (PHA), poly(3-hydroxyalkanoate), poly(3-hydroxypropanoate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), poly(3-hydroxyhexanoate), poly(3-hydroxyheptanoate), poly(3-hydroxyoctanoate), poly(4-hydroxyalknaote), poly(4-hydroxybutyrate), poly(4-hydroxyvalcrate), poly(4-hydroxyhexanote), poly(4hydroxyheptanoate), poly(4-hydroxyoctanoate), 3-hydroxyalknnoate, 4-hydroxyalkanoate monomers, polyester, poly(D,L-lactide), poly(L-lactide), polyglycolide, poly(D,L-lactide-co-glycolide), poly(lactide-co-glycolide), polycaprolactone, poly(lactide-co-caprolactone), poly(glycolide-co-caprolactone), poly(dioxanone), poly(ortho ester), poly(anhydride), poly(tyrosine carbonate), poly(tyrosine ester), poly(imino carbonate), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acid), polycyanoacrylate, poly(trimethylene carbonate) poly(iminocarbonate), polyurethane, polyphosphazene, silicone, polyester, polyolefin, polyisobutylene and ethylene-alphaolefin copolymer, acrylate, vinyl halide. polyvinyl chloride, polyvinyl ether, polyvinyl methyl ether, polyvinylidene halide, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketone, polyvinyl aromatic, polystyrene, polyvinyl ester, polyvinyl acetate, copolymers of vinyl monomers with each other and olefins, ethylene-methyl methacrylate copolymer, acrylonitrile-styrene copolymer, ABS resin, ethylene-vinyl acetate copolymer, polyamide, Nylon 66, polycapro-lactam, alkyd resins, polycarbonate, polyoxymethylene, polyimide, polyether, poly(glyceryl sebacate), poly(propylene fumarate), epoxy resin, polyurethane, rayon, rayon-triacetate, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose pro-pionate, cellulose ether, carboxymethyl cellulose, polyether, copoly(ether ester), PEO/PLA;

polyalkylene oxide, poly(ethylene oxide), poly(propylene oxide), poly(ether ester), polyalkylene oxalates, polyphosphazene, phosphoryl choline, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers, hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropyl methacrylamide, PEG acrylate (PEGA), PEG methacrylate, 2-ethacryloyloxyethylphosphoryl-choline (MPC), n-vinyl pyrrolidone (VP), carboxylic acid bearing monomer, methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylatc, 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-isoprene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene PEG, polycaprolactone-PEG (PCL-PEG). PLA-PEG, poly(methyl methlcrylate)-PEG (PMMA-PEG), polydimethylsiloxane-co-PEG (PDMS-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), PLURONIC™

surfactants (polypropylene oxide-co-polyethylene glycol), poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone).

6. The method of claim 1 where the penetrating agent is selected from the group consisting of peptides, arginine-rich peptides, trans-activation transcriptional activator (Tat) peptides, biocompatible short peptides of naturally occurring amino acids that have the optical and electronic properties of semiconductor nano-crystals, short peptides of phenylalanine with particles consisting of both inorganic or organic materials, mono-layers of phospholipid, bilayers of phospholipid, a protein coating to direct nanoparticles to attach to a cell membrane, a member of a streptavidin-biotin pair, an immunoglobulin, a member of a cell-specific antibody-antigen pair, and combinations thereof.

7. The method of claim 1 where the nanoparticle is configured with an encapsulation and/or coating selected from the group consisting of silicon crosslinked micelles, polymers, (poly)ethyleneglycol (PEG) grafted polyethylenimines (PEI) and derivatives thereof, proton-absorbing polymers, PEG-chitosan and derivatives thereof, folate-chitosan and derivatives thereof, amphiphillic block copolymer micelles crosslinked or uncrosslinked, poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) with a PEO-PPO-PEO structure), and combinations thereof.

8. The method of claim 1 where the penetrating agent is a physiologic biomolecule.

9. The method of claim 8 where the physiologic biomolecule is selected from the group consisting of carbohydrate, cholesterol, glutathione, collagen, chitosan, alginate, fibrin, fibrinogen, cellulose, starch, dextran, dextrin, glycosamino glycan (GAG), polysaccharide, elastin, biotin, hyaluronic acid, heparin, and derivatives and combinations thereof.

10. The method of claim 1 where the penetrating agent is a cell-penetrating peptide (CPP), an activatable cell-penetrating peptide (ACPP), and combinations thereof.

11. The method of claim 10 where the CPP or ACPP is a naturally-occurring or artificially constructed protein segment less than about 30 amino acids rich in arginine, lysine, cysteine, histidine, and/or ornithine and optionally including a penetration accelerating peptide sequence (Pas) or an INF7 fusion peptide sequence.

12. The method of claim 10 where the CPP or ACPP is selected from the group consisting of transportan, penetratin, TAT, VP22, MAP, KALA, ppTG20, proline-rich peptides, MPG-derived peptides, Pep-1, nona-arginine, carboxy-terminal tail of TFPI-2, polyproline helices having cationic amino acids and/or cationic-functionalized amino acids within the helix, guanidinium-functionalized proline, a synthesized oligoarginine cell penetrating peptide based on the HIV-1 Tat protein motif bearing a terminal polyhistidine (His8) tract, oligoguanidinium scaffolds, cationic-functionalized calixarenes or cyclodextrins, arginine-functionalized calixarene, CPP comprising a INF7 fusion peptide and nona-arginine produces IR9/QD and IR9/DNA complexe, IR9, IR9/QD and IR9/DNA.

13. The method of claim 1 where the penetrating agent is a gene capable of modifying cell polarization.

14. The method of claim 13 where the gene encodes a protein selected from the group consisting of a cell membrane ion channel protein or transporter, G protein-coupled receptor, opsin family member, rhodopsin, photopsin, halorhodopsin, a neurotransmitter, glutamate/aspartate transporter, GABA transporter, glycine transporter, monoamine transporter, dopamine transporter, norepinephrine transporter, serotonin transporter, vesicular monoamine transporter.

15. The method of claim 1 where the penetrating agent is an organic or non-organic biodegradable compound.

16. The method of claim 15 where the compound is selected from the group consisting of silicon, porous silicon, aliphatic biodegradable polymer, and combinations thereof.

17. The method of claim 1 where the complex further comprises a biomolecule.

18. The method of claim 1 where the nanoparticle is selected from the group consisting of nanotubes, nanowires, nanocrystals, cadmium/selenium (Cd/Se) nanocrystals, graphene quantum dots, graphene-oxide quantum dots, graphene-zinc oxide quantum dots, graphene nanotubes, carbon nanotubes, and combinations thereof.

19. The method of claim 1 where the nanoparticle is associated with, complexed with, or conjugated to an agent by a linker selected from the group consisting of amino group, carboxyl group, S—

S deprotected sulfhydril groups in biomolecule, bissuccinimide derivative, maleimidosuccinimide/succinimidylpyridyldithio/-halosuccinimide derivative, N-(4-maleimido-phenyl)isocyanate, carbodiimide, sulfosuccinimidylsuberyl, synthetic tripyrrole-peptide, NHS-ester, esters, and combinations thereof.

20. The method of claim 19 where the linker is cleaved to enter a cell by a compound selected from the group consisting of a proteases, a matrix metalloproteinase-2, and combinations thereof.

21. The method of claim 1 where the targeting agent is selected from the group consisting of an antibody, a ligand for a receptor, and combinations thereof.

22. The method of claim 1 where light is applied under conditions to controllably activate the quantum dots by controlling at least one of time of exposure, intensity of exposure, or site of exposure and where the light applied is at least one of ambient light, ultraviolet light, visible light, or infrared light.

23. The method of claim 1 where the therapy is functional recovery and controlled regulated plasma membrane polarization of the cell and is selected from the group consisting of curative, palliative, and remediative, therapeutic, preventive, and combinations thereof.

24. The method of claim 1 where the target agent targets the complex to a specific cell or a specific body region selected from a specific organ, tissue type, and/or cell type, where the targeted location is the site of a disease or a location affected by a disease.

25. The method of claim 1 where the target cell is selected from the group consisting of a neuronal cell, a muscle cell, an ocular cell, an olfactory cell, an auditory cell, a retinal cell, an inferior laryngeal cell, a cardiac cell, and combinations thereof.

26. The method of claim 1 where controllably activating the nanoparticle controllably activates or de-activates an action potential in a cell.

27. The method of claim 1 wherein the individual requires diagnosis and/or therapy for a condition selected from the group consisting of Parkinson'"'"'s or Alzheimer'"'"'s disease with the quantum dots regulating a dopamine-responsive neuron, epilepsy, depression, spreading depression, migraines, mood disorders, restless leg syndrome, schizophrenia, senile dementia, Tourette syndrome, stuttering, cardiac dysrhythmia, and combinations thereof.