Combined nanotechnology and sensor technologies for simultaneous diagnosis and treatment

• US 20050037374A1
• Filed: 12/23/2003
• Published: 02/17/2005
• Est. Priority Date: 11/08/1999
• Status: Abandoned Application

• Current Assignee: University of Florida (State University System of Florida)
• Original Assignee: University of Florida (State University System of Florida)
• Inventors: Melker, Richard J., Dennis, Donn Michael
• Application Number:
  US10/744,789
• Publication Number:
  US 20050037374A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61B 5/00 Measuring for diagnostic purposes radiation diagnosis A61B6/00; diagnosis by ultrasonic, sonic or infrasonic waves A61B8/00; Identification of persons
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61K 47/6931 the material constituting the nanoparticle being a polymer
• 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 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0423 Surface waves, e.g. Rayleigh waves, Love waves
• CPC Class Codes: G01N 2291/0426 Bulk waves, e.g. quartz crystal microbalance, torsional waves
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 29/4481 Neural networks
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Systems and methods for diagnosing and/or treating conditions, diseases, or disorders. The present invention uses nanoparticle-based assemblies, which comprise a nanoparticle; a surrogate marker; and a means for detecting a specific chemical entity. Such nanoparticle-based assemblies combine nanotechnology and sensor technology to provide an efficient and accurate means for diagnosing a condition, disease, or disorder as well as for focused treatment regimens.

Claims

1. A method for diagnosis of a condition, disease, or disorder, comprising:

(a) administering to a patient a composition comprising at least one nanoparticle-based assembly, wherein the nanoparticle-based assembly comprises a nanoparticle;

a surrogate marker, and a means for detecting a specific chemical entity (SCE);

(b) obtaining a sample of bodily fluid from the patient;

(c) applying sensor technology to the sample of bodily fluid to detect the presence of the surrogate marker.

2. The method according to claim 1, wherein the nanoparticle is a nanotube.

3. The method according to claim 1, wherein SCE-detecting means is selected from the group consisting of an antibody, a protein, and an aptamer.

4. The method according to claim 1, wherein the surrogate marker is selected from the group consisting of DMSO, benzodiazepine, a benzodiazepine metabolite, acetaldehyde, acetophenone, anise, benzaldehyde, benzyl alcohol, benzyl cinnamate, cadinene, camphene, camphor, cinnamon, citronellal, cresol, cyclohexane, eucalyptol, and eugenol, eugenyl methyl ether.

5. The method according to claim 1, wherein the surrogate marker is selected from the group consisting of sodium bisulfate, dioctyl sodium sulfosuccinate, polyglycerol polyricinoleic acid, calcium casein peptone-calcium phosphate, botanicals (i.e., chrysanthemum;

licorice;

jellywort, honeysuckle;

lophatherum, mulberry leaf;

frangipani;

selfheal;

sophora flower bud), ferrous bisglycinate chelate, seaweed-derived calcium, DHASCO (docosahexaenoic acid-rich single-cell oil) and ARASCO (arachidonic acid-rich single-cell oil), fructooligosaccharide, trehalose, gamma cyclodextrin, phytosterol esters, gum arabic, potassium bisulfate, stearyl alcohol, erythritol, D-tagatose, and mycoprotein.

6. The method according to claim 1, wherein the bodily fluid sample is selected from the group consisting of exhaled breath, whole blood, blood plasma, urine, semen, saliva, lymph fluid, meningal fluid, amniotic fluid, glandular fluid, sputum, feces, sweat, mucous, and cerebrospinal fluid.

7. The method according to claim 1, wherein the bodily fluid sample is a separated fraction of a solution or mixture containing homogenized solid materials selected from the group consisting of feces, tissues, and biopsy samples.

8. The method according to claim 1, wherein the SCE-detecting means has a specific action on compounds selected from the group consisting of acetaldehyde, acetone, ammonia, carbon monoxide, chloroform, diethylamine, hydrogen, isoprene, methanethiol, methylethylketone, O-toluidine, pentane sulfides and sulfides, H₂S, MeS, Me₂S, α

II-spectrin breakdown products and/or isoprostanes, prostate specific antigen, and GLXA.

9. The method according to claim 1, wherein the SCE-detecting means has a specific action on compounds selected from the group consisting of illicit, illegal, or controlled substances;

allergens;

toxins;

carcinogens;

infectious agents; and

cell markers for diseases.

10. The method according to claim 1, wherein the SCE-detecting means has a specific action on compounds selected from the group consisting of amphetamines, analgesics, barbiturates, club drugs, cocaine, crack cocaine, depressants, designer drugs, ecstasy, Gamma Hydroxy Butyrate, hallucinogens, heroin, morphine, inhalants, ketamine, lysergic acid diethylamide, marijuana, methamphetamines, opiates, narcotics, phencyclidine, prescription drugs, psychedelics, Rohypnol, steroids, stimulants, pollen, spores, dander, peanuts, eggs, shellfish, mercury, lead, other heavy metals, Clostridium Difficile toxin, acetaldehyde, beryllium compounds, chromium, dichlorodiphenyltrichloroethane (DDT), estrogens, N-methyl-N′

-nitro-N-nitrosoguanidine (MNNG), radon, Bordettella bronchiseptica, citrobacter, Escherichia coli, hepatitis viruses, herpes, immunodeficiency viruses, influenza virus, Listeria, micrococcus, mycobacterium, rabies virus, rhinovirus, rubella virus, Salmonella, yellow fever virus, T cell markers, B cell markers, myeloid/monocytic markers, maturity status markers, α

-Fetoprotein, β

2-Microglobulin, and Beta Human Chorionic Gonadotropin (b HCG.

11. The method according to claim 1, wherein the nanoparticle is formed with an interior void that contains the surrogate marker, wherein the nanoparticle has at least one open end to provide access to the interior void.

12. The method according to claim 11, wherein the interior void also contains a payload.

13. The method according to claim 11, wherein the nanoparticles further includes an end-cap to block the open end.

14. The method according to claim 13, wherein the end-cap is a particle that has a maximum dimension of less than 100 μ

m.

15. The method according to claim 13, wherein the end-cap is attached to the nanoparticle by covalent bonds.

16. The method according to claim 13, wherein the nanoparticle is in the form of a tubular body;

and wherein the SCE-detecting means is attached to the end-cap.

17. The method according to claim 1, wherein the nanoparticle is composed of silica.

18. The method according to claim 1, wherein the nanoparticle is composed of a polymer.

19. The method according to claim 18, wherein the SCE-detecting means is attached to a surface of the nanoparticle using copolymerization.

20. The method according to claim 18, wherein the polymer nanoparticle is composed of polymers selected from the group consisting of polystyrene, polyorganosiloxane, poly(methyl methacrylate), polystyrene, polylactic acids, and other biodegradable polymers, acrylic latexes, polyorganosiloxane, cellulose, polyethylene, poly(vinyl chloride), poly(ethyl methacrylate), poly(tetrafluoroethylene), poly(4-iodostyrene/divinylbenzene), poly(4-vinylpyridine/divinylbenzene), poly(styrene/divinyl benzene), crosslinked melamine particles, phenolic polymer colloids, polyamide 6/6, natural rubber, and naturally occurring biopolymers.

21. The method according to claim 18, wherein the polymer nanoparticle is composed of biodegradable polymers selected from the group consisting of poly(caprolactone), poly(glycolic acid), poly(lactic acid), poly(hydroxybutryate), poly(adipic anhydride), poly(maleic anhydride), polydioxanone, polyamines, polyamides, polyurethanes, polyesteramides, polyorthoesters, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, poly(methyl vinyl ether), poly(alkylene oxalate), poly(alkylene succinate), polyhydroxycellulose, chitin, chitosan, and copolymers.

22. The method according to claim 18, wherein the polymer nanoparticle is composed of biocompatible polymers selected from the group consisting of poly(lactide-co-glycolide), poly(ethylene glycol), and copolymers of poly(ethylene oxide) with poly(L-Lactic acid) or with poly(3-benzyl-L-aspartate.

23. The method according to claim 1, wherein the SCE-detecting means is incorporated into the nanoparticle.

24. The method according to claim 1, wherein the nanoparticle is produced in a shape selected from a group consisting of spherical;

elliptical;

cubic;

cylindrical;

tetrahedron;

polyhedral;

irregular-prismatic;

icosahedral; and

cubo-octahedral.

25. The method according to claim 1, wherein the nanoparticle has a dimension less than 500 nm.

26. The method according to claim 1, wherein the surface of the nanoparticle is stealthy.

27. A method for diagnosis and treatment of a condition, disease, or disorder, comprising:

(a) administering to a patient a composition comprising at least one nanoparticle-based assembly, wherein the nanoparticle-based assembly comprises a nanoparticle;

a surrogate marker, a means for detecting a specific chemical entity (SCE), and a payload;

(b) obtaining a sample of bodily fluid from the patient;

(c) applying sensor technology to the sample of bodily fluid to detect the presence of the surrogate marker.

28. The method according to claim 27, wherein the nanoparticle is a nanotube.

29. The method according to claim 27, wherein SCE-detecting means is selected from the group consisting of an antibody, a protein, and an aptamer.

30. The method according to claim 27, wherein the surrogate marker is selected from the group consisting of benzodiazepine, a benzodiazepine metabolite, acetaldehyde, DMSO, acetophenone, anise, benzaldehyde, benzyl alcohol, benzyl cinnamate, cadinene, camphene, camphor, cinnamon, citronellal, cresol, cyclohexane, eucalyptol, and eugenol, eugenyl methyl ether.

31. The method according to claim 27, wherein the surrogate marker is selected from the group consisting of sodium bisulfate, dioctyl sodium sulfosuccinate, polyglycerol polyricinoleic acid, calcium casein peptone-calcium phosphate, botanicals (i.e., chrysanthemum;

licorice;

jellywort, honeysuckle;

lophatherum, mulberry leaf;

frangipani;

selfheal;

sophora flower bud), ferrous bisglycinate chelate, seaweed-derived calcium, DHASCO (docosahexaenoic acid-rich single-cell oil) and ARASCO (arachidonic acid-rich single-cell oil), fructooligosaccharide, trehalose, gamma cyclodextrin, phytosterol esters, gum arabic, potassium bisulfate, stearyl alcohol, erythritol, D-tagatose, and mycoprotein.

32. The method according to claim 27, wherein the bodily fluid sample is selected from the group consisting of exhaled breath, whole blood, blood plasma, urine, semen, saliva, lymph fluid, meningal fluid, amniotic fluid, glandular fluid, sputum, feces, sweat, mucous, and cerebrospinal fluid.

33. The method according to claim 27, wherein the bodily fluid sample is a separated fraction of a solution or mixture containing homogenized solid materials selected from the group consisting of feces, tissues, and biopsy samples.

34. The method according to claim 27, wherein the SCE-detecting means has a specific action on compounds selected from the group consisting of acetaldehyde, acetone, ammonia, carbon monoxide, chloroform, diethylamine, hydrogen, isoprene, methanethiol, methylethylketone, O-toluidine, pentane sulfides and sulfides, H₂S, MeS, Me₂S, α

II-spectrin breakdown products and/or isoprostanes, prostate specific antigen, and GLXA.

35. The method according to claim 27, wherein the SCE-detecting means has a specific action on compounds selected from the group consisting of illicit, illegal, or controlled substances;

allergens;

toxins;

carcinogens;

infectious agents; and

cell markers for diseases.

36. The method according to claim 27, wherein the SCE-detecting means has a specific action on compounds selected from the group consisting of amphetamines, analgesics, barbiturates, club drugs, cocaine, crack cocaine, depressants, designer drugs, ecstasy, Gamma Hydroxy Butyrate, hallucinogens, heroin, morphine, inhalants, ketamine, lysergic acid diethylamide, marijuana, methamphetamines, opiates, narcotics, phencyclidine, prescription drugs, psychedelics, Rohypnol, steroids, stimulants, pollen, spores, dander, peanuts, eggs, shellfish, mercury, lead, other heavy metals, Clostridium Difficile toxin, acetaldehyde, beryllium compounds, chromium, dichlorodiphenyltrichloroethane (DDT), estrogens, N-methyl-N′

-nitro-N-nitrosoguanidine (MNNG), radon, Bordettella bronchiseptica, citrobacter, Escherichia coli, hepatitis viruses, herpes, immunodeficiency viruses, influenza virus, Listeria, micrococcus, mycobacterium, rabies virus, rhinovirus, rubella virus, Salmonella, yellow fever virus, T cell markers, B cell markers, myeloid/monocytic markers, maturity status markers, α

-Fetoprotein, β

2-Microglobulin, and Beta Human Chorionic Gonadotropin (b HCG.

37. The method according to claim 27, wherein the nanoparticle is formed with an interior void that contains the surrogate marker, wherein the nanoparticle has at least one open end to provide access to the interior void.

38. The method according to claim 37, wherein the interior void also contains a payload.

39. The method according to claim 37, wherein the nanoparticles further includes an end-cap to block the open end.

40. The method according to claim 39, wherein the end-cap is a particle that has a maximum dimension of less than 100 μ

m.

41. The method according to claim 39, wherein the end-cap is attached to the nanoparticle by covalent bonds.

42. The method according to claim 39, wherein the nanoparticle is in the form of a tubular body;

and wherein the SCE-detecting means is attached to the end-cap.

43. The method according to claim 27, wherein the nanoparticle is composed of silica.

44. The method according to claim 27, wherein the nanoparticle is composed of a polymer.

45. The method according to claim 44, wherein the SCE-detecting means is attached to a surface of the nanoparticle using copolymerization.

46. The method according to claim 44, wherein the polymer nanoparticle is composed of polymers selected from the group consisting of polystyrene, polyorganosiloxane, poly(methyl methacrylate), polystyrene, polylactic acids, and other biodegradable polymers, acrylic latexes, polyorganosiloxane, cellulose, polyethylene, poly(vinyl chloride), poly(ethyl methacrylate), poly(tetrafluoroethylene), poly(4-iodostyrene/divinylbenzene), poly(4-vinylpyridine/divinylbenzene), poly(styrene/divinyl benzene), crosslinked melamine particles, phenolic polymer colloids, polyamide 6/6, natural rubber, and naturally occurring biopolymers.

47. The method according to claim 44, wherein the polymer nanoparticle is composed of biodegradable polymers selected from the group consisting of poly(caprolactone), poly(glycolic acid), poly(lactic acid), poly(hydroxybutryate), poly(adipic anhydride), poly(maleic anhydride), polydioxanone, polyamines, polyamides, polyurethanes, polyesteramides, polyorthoesters, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, poly(methyl vinyl ether), poly(alkylene oxalate), poly(alkylene succinate), polyhydroxycellulose, chitin, chitosan, and copolymers.

48. The method according to claim 44, wherein the polymer nanoparticle is composed of biocompatible polymers selected from the group consisting of poly(lactide-co-glycolide), poly(ethylene glycol), and copolymers of poly(ethylene oxide) with poly(L-Lactic acid) or with poly(β

-benzyl-L-aspartate.

49. The method according to claim 27, wherein the SCE-detecting means is incorporated into the nanoparticle.

50. The method according to claim 27, wherein the nanoparticle is produced in a shape selected from a group consisting of spherical;

elliptical;

cubic;

cylindrical;

tetrahedron;

polyhedral;

irregular-prismatic;

icosahedral; and

cubo-octahedral.

51. The method according to claim 27, wherein the nanoparticle has a dimension less than 500 nm.

52. The method according to claim 27, wherein the surface of the nanoparticle is stealthy.

53. The method according to claim 27, wherein the payload is selected from the group consisting of genetic materials;

RNA;

oligonucleotides;

polynucleotides;

peptides;

proteins;

enzymes;

hormones;

steroids;

chemotherapeutics;

antibiotics;

antifungal agents;

anesthetics;

immunomodulators;

anti-inflammatory agents;

pain relieving agents;

autonomic drugs;

cardiovascular-renal drugs;

endocrine drugs;

hematopoietic growth factors;

blood lipid lowering drugs;

AIDS drugs;

modulators of smooth muscle function;

antileptics;

psychoactive drugs; and

drugs that act on the peripheral nerves, adrenergic receptors, cholinergic receptors, the skeletal muscles, the cardiovascular system, smooth muscles, the blood circulatory system, synoptic sites, neuroeffector junctional sites, endocrine and hormone systems, metabolic systems, the immunological system, the reproductive system, the skeletal system, autacoid systems, the alimentary and excretory systems, the histamine system, and the central nervous system.

54. The method according to claim 53, wherein the payload is selected from the group consisting of prochlorperzine edisylate, ferrous sulfate, aminocaproic acid, mecamylamine hydrochloride, procainamide hydrochloride, amphetamine sulfate, methamphetamine hydrochloride, benzamphetamine hydrochloride, isoproterenol sulfate, phenmetrazine hydrochloride, bethanechol chloride, methacholine chloride, pilocarpine hydrochloride, atropine sulfate, scopolamine bromide, isopropamide iodide, tridihexethyl chloride, phenformin hydrochloride, methylphenidate hydrochloride, theophylline cholinate, cephalexin hydrochloride, diphenidol, meclizine hydrochloride, prochlorperazine maleate, phenoxybenzamine, thiethylperzine maleate, anisindone, diphenadione erthyrityl tetranitrate, digoxin, Intal (disodium cromoglycate), codeine, morphine, sodium salicylate, salicylic acid, meperidine hydrochloride (DEMEROL), chlophedianol hydrochloride, epinephrine, isoproterenol, salbutamol, terbutaline, ephedrine, aminophylline, acetylcysteine, sulfanilamide, sulfadiazine, tetracycline, rifampin (rifamycin), dihydrostreptomycin, p-aminosalicylic acid, hypoglycemics tolbutamide (ORINASE), prednisone, prednisolone, prednisolone metasulfobenzoate, chlorambucil, busulfan, alkaloids, antimetabolites, 6-mercaptopurine, thioguanine, 5-fluorouracil, hydroxyurea, isoflurophate, acetazolamide, methazolamide, bendroflumethiazide, chloropromaide, tolazamide, chlormadinone acetate, phenaglycodol, allopurinol, aluminum aspirin, methotrexate, acetyl sulfisoxazole, erthyromycin, hydrocortisone, hydrocorticosterone acetate, cortisone acetate, dexamethasone and its derivatives such as betamethasone, triamcinolone, methyltestosterone, 17-S-estradiol, ethinyl estradiol, ethinyl estradiol 3-methyl ether, 17-α

-hydroxygrogesterone acetate, 19-norprogesterone, norgestrel, norethindrone, norethisterone, norethiederone, progesterone, norgesterone, norethynodrel, aspirin, indomethacin, naproxen, fenoprofen, sulindac, indoprofen, nitroglycerin, isosorbide dinitrate, propranolol, timolol, atenolol, alprenolol, crimetidine, clonidine, imipramine, levodopa, chlorpromazine, methyldopa, dihydroxyphenylanine, theophylline, calcium gluconate, ketoprofen, ibuprofen, cephalexin, erythromycin, haloperidol, zomepirac, ferrous lactate, vincamine, phenoxybenzamine, diltiazem, milrinone, mandol, quanbenz, hydrochlorothiazide, ranitidine, flurbiprofen, fenufen, fluprofen, tolmetin, alclofenac, mefenamic, flufenamic, difuinal, nimodipine, nitrendipine, nisoldipine, nicardipine, felodipine, lidoflazine, tiapamil, gallopamil, amlodipine, mioflazine, lisinolpril, enalapril, enalaprilat captopril, ramipril, famotidine, nizatidine, sucralfate, etintidine, tetratolol, minoxidil, chlordiazepoxide, diazepam, amitriptyline, and imipramine.

55. The method according to claim 53, wherein the payload is selected from the group consisting of bone morphogenic proteins, insulin, colchicines, glucagons, thyroid stimulating hormone, parathyroid hormones, pituitary hormones, calcitonin, rennin, prolactin, corticotrophin, thyrotropic hormone, follicle stimulating hormone, chorionic gonadotropin, gonadotropin releasing hormone, bovine somatotropin, porcine somatotropin, oxytocin, vasopressin, GRF, somatostatin, lypressin, pancreozymin, luteinizing hormone, LHRH, LHRH agonists and antagonists, leuprolide, interferons, consensus interferon, interleukins, growth hormones, bovine growth hormone, porcine growth hormone, fertility inhibitors, fertility promoters, growth factors, coagulation factors, and human pancreas hormone releasing factor.

56. The method according to claim 53, wherein the payload is a chemotherapeutic selected from the group consisting of carboplatin, cisplatin, paclitaxel, BCNU, vincrtistine, camptothecin, etopside, cytokines, ribozymes, interferons, oligonucleotides, and oligonucleotides that inhibit translation or transcription of tumor genes.