CN113797334A - Artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material and preparation and application thereof - Google Patents
Artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material and preparation and application thereof Download PDFInfo
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- CN113797334A CN113797334A CN202010469470.8A CN202010469470A CN113797334A CN 113797334 A CN113797334 A CN 113797334A CN 202010469470 A CN202010469470 A CN 202010469470A CN 113797334 A CN113797334 A CN 113797334A
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- artemisinin
- indocyanine green
- solution
- composite material
- nitrate
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- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 title claims abstract description 109
- 229960004191 artemisinin Drugs 0.000 title claims abstract description 109
- 229930101531 artemisinin Natural products 0.000 title claims abstract description 109
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 title claims abstract description 100
- 229960004657 indocyanine green Drugs 0.000 title claims abstract description 100
- 239000002131 composite material Substances 0.000 title claims abstract description 96
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 title claims abstract description 95
- 229960001545 hydrotalcite Drugs 0.000 title claims abstract description 95
- 229910001701 hydrotalcite Inorganic materials 0.000 title claims abstract description 95
- 239000002135 nanosheet Substances 0.000 title claims abstract description 92
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 60
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 20
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 18
- 229910001960 metal nitrate Inorganic materials 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 239000008367 deionised water Substances 0.000 claims description 12
- 229910021641 deionized water Inorganic materials 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 11
- 235000010344 sodium nitrate Nutrition 0.000 claims description 11
- 239000004317 sodium nitrate Substances 0.000 claims description 11
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 10
- 229920001223 polyethylene glycol Polymers 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 229910002651 NO3 Inorganic materials 0.000 claims description 7
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 7
- 239000011261 inert gas Substances 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 229910021645 metal ion Inorganic materials 0.000 claims description 6
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 230000001376 precipitating effect Effects 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 150000001450 anions Chemical class 0.000 claims description 4
- PHFQLYPOURZARY-UHFFFAOYSA-N chromium trinitrate Chemical compound [Cr+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O PHFQLYPOURZARY-UHFFFAOYSA-N 0.000 claims description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 4
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 claims description 4
- 239000002002 slurry Substances 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 claims description 3
- MYLBTCQBKAKUTJ-UHFFFAOYSA-N 7-methyl-6,8-bis(methylsulfanyl)pyrrolo[1,2-a]pyrazine Chemical compound C1=CN=CC2=C(SC)C(C)=C(SC)N21 MYLBTCQBKAKUTJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- UFMZWBIQTDUYBN-UHFFFAOYSA-N cobalt dinitrate Chemical compound [Co+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O UFMZWBIQTDUYBN-UHFFFAOYSA-N 0.000 claims description 3
- 229910001981 cobalt nitrate Inorganic materials 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- 229920000331 Polyhydroxybutyrate Polymers 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 239000011229 interlayer Substances 0.000 claims description 2
- MIVBAHRSNUNMPP-UHFFFAOYSA-N manganese(2+);dinitrate Chemical compound [Mn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MIVBAHRSNUNMPP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229910052754 neon Inorganic materials 0.000 claims description 2
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 2
- 239000005015 poly(hydroxybutyrate) Substances 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 239000004633 polyglycolic acid Substances 0.000 claims description 2
- 239000004626 polylactic acid Substances 0.000 claims description 2
- 238000011282 treatment Methods 0.000 abstract description 36
- 238000003384 imaging method Methods 0.000 abstract description 19
- 238000003756 stirring Methods 0.000 abstract description 13
- 210000004881 tumor cell Anatomy 0.000 abstract description 8
- 230000002195 synergetic effect Effects 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 238000003759 clinical diagnosis Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 52
- 239000000463 material Substances 0.000 description 42
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 19
- 239000001301 oxygen Substances 0.000 description 19
- 229910052760 oxygen Inorganic materials 0.000 description 19
- 238000000799 fluorescence microscopy Methods 0.000 description 17
- 239000003814 drug Substances 0.000 description 16
- 229940079593 drug Drugs 0.000 description 15
- MFUVDXOKPBAHMC-UHFFFAOYSA-N magnesium;dinitrate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MFUVDXOKPBAHMC-UHFFFAOYSA-N 0.000 description 12
- 239000000084 colloidal system Substances 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 6
- 238000002428 photodynamic therapy Methods 0.000 description 6
- 238000007626 photothermal therapy Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- ZKSVYBRJSMBDMV-UHFFFAOYSA-N 1,3-diphenyl-2-benzofuran Chemical compound C1=CC=CC=C1C1=C2C=CC=CC2=C(C=2C=CC=CC=2)O1 ZKSVYBRJSMBDMV-UHFFFAOYSA-N 0.000 description 4
- 150000001723 carbon free-radicals Chemical class 0.000 description 4
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- 229910001448 ferrous ion Inorganic materials 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
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- XNDZQQSKSQTQQD-UHFFFAOYSA-N 3-methylcyclohex-2-en-1-ol Chemical compound CC1=CC(O)CCC1 XNDZQQSKSQTQQD-UHFFFAOYSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000000078 anti-malarial effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
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- 235000001405 Artemisia annua Nutrition 0.000 description 1
- 240000000011 Artemisia annua Species 0.000 description 1
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- 206010063094 Cerebral malaria Diseases 0.000 description 1
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- 238000004435 EPR spectroscopy Methods 0.000 description 1
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- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
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- BBXXLROWFHWFQY-UHFFFAOYSA-N ethirimol Chemical compound CCCCC1=C(C)NC(NCC)=NC1=O BBXXLROWFHWFQY-UHFFFAOYSA-N 0.000 description 1
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- MVFCKEFYUDZOCX-UHFFFAOYSA-N iron(2+);dinitrate Chemical compound [Fe+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MVFCKEFYUDZOCX-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
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- 239000002114 nanocomposite Substances 0.000 description 1
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- KBJMLQFLOWQJNF-UHFFFAOYSA-N nickel(ii) nitrate Chemical compound [Ni+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O KBJMLQFLOWQJNF-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
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- 229930009674 sesquiterpene lactone Natural products 0.000 description 1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Abstract
The invention discloses an artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material as well as preparation and application thereof. The composite material comprises: ultrathin hydrotalcite nanosheets, and artemisinin or polymer-protected artemisinin and indocyanine green loaded thereon. The preparation method comprises the following steps: firstly, synthesizing ultrathin hydrotalcite nanosheets by a top-down method, and then ultrasonically stirring functional molecules such as artemisinin and indocyanine green and the ultrathin hydrotalcite nanosheets to synthesize the composite material. The composite material realizes near infrared under the irradiation of near infrared light, and effectively kills tumor cells while performing photoacoustic imaging; wherein the artemisinin can further enhance the therapeutic efficiency of the composite product. The reagent is expected to be used for clinical diagnosis and synergistic treatment of tumors.
Description
Technical Field
The invention belongs to the technical field of preparation of cancer treatment medicines. More particularly, relates to an artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material, and preparation and application thereof.
Background
Cancer is one of the diseases which seriously threaten the life safety of human beings in the world at present, and the death rate is extremely high. Traditional treatments such as surgical resection, radiation therapy, chemotherapy, etc. often have strong side effects on normal tissues and the immune system. Based on the defects of the traditional treatment methods, several new treatment methods such as photodynamic therapy (PDT), photothermal therapy (PTT), chemokinetic therapy (CDT), immunotherapy and the like have better treatment effects on tumors. Among them, photodynamic therapy can selectively destroy tumor sites and has stronger controllability, compared with the traditional therapy, photodynamic therapy has some advantages, such as being used for sites where surgical excision can not be carried out; part of photosensitizer has low toxicity, can be successfully metabolized to the outside of the body after liver and kidney are gathered, can not cause damage to organs, and the like, at present, the photodynamic therapy (PDT) carried out by the photosensitizer (chem.Soc.Rev.2011,40, 340-. In addition, the photothermal therapy research materials are various, such as organic near infrared dyes (Biomaterials 2017,133, 208-. However, the light stability is poor, the photothermal conversion efficiency is not high, and the price is high, so that the further application of the medicines is limited.
However, as an efficient drug carrier, the ultrathin hydrotalcite nanosheet (CN201811409530.6) has abundant hydroxyl groups on the surface, so that the interaction with the guest molecule can be significantly enhanced, and a good two-dimensional confinement effect is exhibited, thereby enhancing the stability and efficiency of the guest molecule. Compared with traditional drug carriers such as silicon dioxide (adv. Funct. Mater.2015,25: 384-; and because the hydrotalcite layer plate is positively charged and the cell membrane is negatively charged, the hydrotalcite layer plate can more easily enter cells through electrostatic attraction, and the uptake of the cells is effectively improved. The hydrotalcite can be biodegraded in tumor cells, so that the guest molecules can be slowly released, and the effect of slowly releasing the medicine at the focus part is achieved. A large number of researches show that the ultrathin hydrotalcite nanosheet not only has good biocompatibility (Nanoscale,2016,8,9815), but also has high drug loading capacity (adv.Mater.2018,30,1707389). Therefore, the problems of unstable drug molecules and targeted therapy can be effectively solved by using the ultrathin hydrotalcite nanosheets as the carriers.
Indocyanine green (ICG) is the only near-infrared fluorescent contrast agent approved by the U.S. Food and Drug Administration (FDA) for clinical use. Clinically, ICG is widely used for auxiliary diagnosis of liver function, cardiac output, and retinal vasculature. The ICG can be used as a near-infrared fluorescent probe because the emission wavelength of the ICG is 820nm, can emit red light after absorbing light energy, can also generate singlet oxygen (adv. Mater.2018,30,1707389) and heat energy (CN201710103519.6) as a photosensitive substance, can be applied to photodynamic therapy and photothermal therapy, and can also be used as a photoacoustic imaging contrast agent (CN201710373187.3) to kill tumor cells. However, indocyanine green is very unstable in aqueous solution, readily forms a dimer between molecules to cause quenching of fluorescence, and is easily rapidly cleared in blood circulation. These deficiencies limit the use of indocyanine green in the diagnosis and treatment of tumors. Therefore, it is necessary to research various nano materials as carriers to load indocyanine green so as to improve the stability of ICG, prolong the blood circulation time of ICG and endow ICG with tumor targeting. Artemisinin (Art) was discovered by U.yo-yo of Chinese pharmacy in 1971 and is a colorless needle crystal of sesquiterpene lactone with peroxy group extracted from stem and leaf of Artemisia annua L. Artemisinin is the most effective antimalarial specific drug (CN201910888053.4) after ethirimol, chloroquine and cyproquine, has the characteristics of quick response and low toxicity particularly for resisting chloroquine malaria and cerebral malaria, and is called as the 'only effective malaria treatment drug in the world' by the world health organization. Recent researches show that artemisinin not only has good antimalarial activity but also has good anti-tumor property (CN200910158927.7), and artemisinin can induce apoptosis of various cancer cells such as breast cancer cells, liver cancer cells, cervical cancer cells and the like and has a relatively obvious inhibition effect on the growth of the cancer cells (ACS appl. Therefore, the combination therapy of carrying two drug molecules to the focus by selecting proper drug carriers is an effective cancer treatment mode.
Disclosure of Invention
Based on the background technology, the invention provides an artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material, and preparation and application thereof.
The artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared by taking ultrathin hydrotalcite nanosheets as a carrier and loading a drug. Wherein, because the tumor cells need to multiply, more ferrous ions can be taken up, and after the artemisinin enters the tumor cells, the artemisinin reacts with endogenous ferrous ions to generate carbon free radicals with cytotoxicity, and the carbon free radicals can generate a large amount of active oxygen species by cooperating with indocyanine green to treat tumors. The material can be applied to photodynamic therapy and photothermal therapy and simultaneously has the effect of chemokinetic therapy.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides an artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material, which comprises: ultrathin hydrotalcite nanosheets, and artemisinin or polymer-protected artemisinin and indocyanine green loaded thereon.
In the composite material, artemisinin molecules or artemisinin molecules protected by a polymer and indocyanine green drug molecules are uniformly distributed on a nano-chip. Due to the two-dimensional confinement effect of the hydrotalcite nanosheets, the efficiency of generating singlet oxygen of artemisinin and indocyanine green can be effectively increased, and artemisinin can react with ferrous ions in tumor cells to generate a large number of carbon free radicals, so that synergistic tumor treatment can be realized.
Based on the composite material of the present invention, preferably, the polymer comprises polyvinyl alcohol resin (MW: 16000-.
Based on the composite material, preferably, the load capacity of the artemisinin and the indocyanine green on the ultrathin hydrotalcite nanosheets is 5-25%; the mass ratio of the artemisinin to the indocyanine green is 0.25-4; wherein, the artemisinin is a drug molecule without polymer.
Based on the composite material of the invention, preferably, the size of the ultrathin hydrotalcite nano-sheet is 50-100nm, the thickness is 1-2nm, the ultrathin hydrotalcite nano-sheet is a layered double hydroxide, and the chemical composition of the ultrathin hydrotalcite nano-sheet is expressed as [ MⅡ 1-xMⅢ x(OH)2]An- z/n·yH2O；
Wherein M isⅡ、MⅢRespectively a divalent metal ion and a trivalent metal ion which are positively charged, wherein the divalent metal ion is selected from Mg2+、Fe2+、Zn2+、Mn2+Or Co2+Wherein the trivalent metal ion is selected from Al3+、Fe3+Or Cr3+One of (1);
x is MⅡ/(MⅡ+MⅢ) The molar ratio of (a) is 1/3-1/4;
y is the amount of crystal water and ranges from 0 to 10;
An-is an interlayer anion, n-is the valence of the anion, in the present invention NO3 -。
The size range of the composite material loaded with the artemisinin and the indocyanine green is still 50-100nm, and the thickness is slightly increased.
Based on the composite material of the present invention, preferably, M isⅡ、MⅢAre each Mg2+And Al3+The anion being NO3 -。
In a second aspect, the invention provides a preparation method of the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material, which comprises the following steps:
1) uniformly mixing a metal nitrate solution and a sodium nitrate solution containing formamide, and adjusting the pH to 8-10 by using a sodium hydroxide solution; reacting for 1-60min at a certain temperature, centrifuging the obtained slurry, precipitating, washing, drying, and dissolving in deionized water to obtain an ultrathin hydrotalcite nanosheet colloidal solution;
2) sequentially adding an indocyanine green solution and an artemisinin solution or a polymer-protected artemisinin solution into the ultrathin hydrotalcite nanosheet colloidal solution obtained in the step 1), reacting in a dark place for 1-12h under inert gas, centrifuging the obtained slurry, precipitating, washing, and dispersing into water to obtain the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material.
The preparation method uses the ultrathin hydrotalcite nanosheet as a carrier, and the composite material can be obtained by mechanically stirring and centrifuging a drug molecular solution and a hydrotalcite nanosheet colloidal solution. Simple process, low energy consumption, low equipment requirement and environmental protection.
Based on the preparation method of the present invention, preferably, in step 1), the metal nitrate solution includes a divalent metal nitrate and a trivalent metal nitrate;
the divalent metal nitrate is selected from one of magnesium nitrate, ferrous nitrate, zinc nitrate, manganese nitrate or cobalt nitrate, and the trivalent metal nitrate is selected from one of ferric nitrate, aluminum nitrate or chromium nitrate.
Based on the preparation method, preferably, the mass concentration of the metal nitrate solution is 1-2.5%, and the solvent is water; in the formamide-containing sodium nitrate solution, the mass concentration of sodium nitrate is 0.05-0.15%, the mass concentration of formamide is 20-25%, and the solvent is water; the mass concentration of the sodium hydroxide solution is 1-2%, and the solvent is water.
Based on the preparation method of the invention, the molar ratio of the divalent metal nitrate, the trivalent metal nitrate and the sodium nitrate is preferably (1-X): x: 2X, wherein X is 1/3-1/4.
Based on the preparation method, the mass ratio of the polymer to the artemisinin is preferably 2: 1-10: 1.
Based on the preparation method of the present invention, preferably, the polymer-protected artemisinin solution is prepared by the following steps:
firstly, preparing a polymer aqueous solution with a certain mass concentration, and then dispersing artemisinin in the polymer aqueous solution; wherein the mass concentration of the polymer is 0.1-2%, and the mass concentration of the artemisinin is 0.01-0.2%.
Based on the preparation method, the mass concentration of the indocyanine green solution is preferably 0.01-0.2%, and the solvent is water.
Based on the preparation method of the present invention, preferably, the inert gas includes one or more of helium, neon, and argon.
Based on the preparation method of the present invention, preferably, the washed solvent in step 1) includes deionized water and absolute ethanol; the washed solvent in step 2) comprises deionized water.
In a third aspect, the invention provides an application of the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material in tumor treatment. In the composite material, due to the two-dimensional confinement effect of the hydrotalcite nanosheets, the efficiency of generating singlet oxygen of artemisinin and indocyanine green can be effectively increased, and artemisinin can react with ferrous ions in tumor cells to generate a large number of carbon free radicals, so that synergistic tumor treatment can be realized.
The invention has the following beneficial effects:
the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material can simultaneously realize photodynamic/photothermal/chemodynamic synergistic treatment, the two-dimensional confinement effect of the ultrathin hydrotalcite nanosheets effectively improves the singlet oxygen generation efficiency of the indocyanine green and the artemisinin, enhances the drug uptake rate of tumor cells, further effectively improves the chemokinetic treatment effect, and has small toxicity and good cancer treatment effect.
The invention provides a simple and convenient preparation method of an artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material; the method is simple and controllable in conditions.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
Fig. 1 is a transmission electron microscope image of the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite synthesized in example 1.
Fig. 2 is a photo-thermal conversion curve of the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite synthesized in example 1.
Fig. 3 is an absorption spectrum diagram of the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material synthesized in example 1, which uses DPBF as a probe to detect singlet oxygen.
Fig. 4 shows the amount of singlet oxygen generated by the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material synthesized in example 1 under different illumination times with pure indocyanine green (with DPBF as a probe).
FIG. 5 is an electron spin resonance diagram of the artemisinin/ultrathin hydrotalcite nanosheet composite synthesized in example 1.
Detailed Description
In order to make the technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in detail with reference to the accompanying drawings.
It is noted that all numerical designations of the invention (e.g., temperature, time, concentration, weight, and the like, including ranges for each) may generally be approximations that vary (+) or (-) by increments of 0.1 or 1.0, as appropriate. All numerical designations should be understood as preceded by the term "about".
Example 1
The preparation method of the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material comprises the following steps:
1) dissolving 0.4096g of magnesium nitrate hexahydrate and 0.1692g of aluminum nitrate nonahydrate in 40mL of water, and uniformly mixing to obtain solution A; dissolving 0.034g of sodium nitrate in 40mL of water containing 25% of formamide, and uniformly mixing to obtain solution B; dissolving 0.35g of sodium hydroxide in 35mL of water, and uniformly mixing to obtain solution C; slowly adding the solution A into the solution B under stirring in water bath at 80 ℃, then dropwise adding the solution C, adjusting the pH to 9, mechanically stirring and reacting for 10min at room temperature, centrifuging for 10min by using a centrifuge with the rotation speed of 8000-10000rpm/s, washing the obtained precipitate for 2 times by using deionized water and absolute ethyl alcohol respectively, and performing centrifugal separation. Drying in a drying oven at 60 ℃ for 6h, and dispersing in water to obtain hydrotalcite nanosheet colloid, wherein the mass concentration of the hydrotalcite nanosheets in the colloid is 1 mg/mL.
2) Taking 10mL of the hydrotalcite nanosheet colloidal solution obtained in the step 1), dissolving 1mg of artemisinin in 1mL of polyethylene glycol aqueous solution with the mass concentration of 1%, dissolving 1mg of indocyanine green in 1mL of deionized water, respectively adding 250 μ L of artemisinin solution and 250 μ L of indocyanine green solution into 10mL of hydrotalcite nanosheet colloid under Ar inert gas, stirring with magnetons in the dark for 12h, centrifuging, washing, separating, and then re-dispersing the precipitate into water to obtain the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material.
In the embodiment, a transmission electron microscope image of the prepared artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material is shown in fig. 1. FIG. 1 shows that the composite material has a uniform size of 50-80 nm. This was dispersed in water and subjected to photo-thermal conversion by laser irradiation at 808nm as shown in FIG. 2. The composite material exhibits excellent photothermal conversion capability, and as the material concentration increases, the photothermal conversion temperature increases. On the other hand, the generation of singlet oxygen is detected by using DPBF as a probe, as shown in FIG. 3, after 808nm illumination, the absorption of DPBF is obviously reduced along with the prolonging of illumination time, which indicates that the composite material has a better singlet oxygen generation effect, FIG. 4 shows the singlet oxygen generation trend of pure indocyanine green and the nano composite material, and compared with the pure indocyanine green, the composite material shows a stronger generation amount of active oxygen species. And the electron spin resonance spectrum also proves the ROS (reactive oxygen species) generating capacity of the artemisinin, as shown in figure 4, the existence of the ultrathin hydrotalcite nanosheets obviously improves the ROS generation of the artemisinin.
Example 2
The preparation method of the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material comprises the following steps:
1) dissolving 0.4096g of magnesium nitrate hexahydrate and 0.1692g of aluminum nitrate nonahydrate in 40mL of water, and uniformly mixing to obtain solution A; dissolving 0.034g of sodium nitrate in 40mL of water containing 25% of formamide, and uniformly mixing to obtain solution B; dissolving 0.35g of sodium hydroxide in 35mL of water, and uniformly mixing to obtain solution C; slowly adding the solution A into the solution B under the stirring of water bath at 80 ℃, then dropwise adding the solution C, adjusting the pH to 9, mechanically stirring and reacting for 10min at room temperature, centrifuging for 10min by using a centrifuge with the rotation speed of 8000 plus 10000rpm/s, respectively washing the obtained precipitate for 2 times by using deionized water and absolute ethyl alcohol, drying for 6h in a vacuum drying oven at 60 ℃, and re-dispersing to water to obtain hydrotalcite nanosheet colloid, wherein the mass concentration of the hydrotalcite nanosheets in the colloid is 1 mg/mL.
2) Taking 10mL of the hydrotalcite nanosheet colloidal solution obtained in the step 1), dissolving 1mg of artemisinin in 1mL of polyethylene glycol aqueous solution with the mass concentration of 1%, dissolving 1mg of indocyanine green in 1mL of deionized water, respectively adding 200 mu L of artemisinin solution and 300 mu L of indocyanine green solution into 10mL of hydrotalcite nanosheet colloid under the inert gas Ar, stirring with magnetons for 12h in the dark, centrifuging, washing, separating, precipitating and dispersing in water to obtain the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material.
The size of the obtained artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is 50-80 nm. The material is dispersed in water, and under the irradiation of a 808nm laser, the material has good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 3
The preparation method of the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material comprises the following steps:
1) dissolving 0.4096g of magnesium nitrate hexahydrate and 0.1692g of aluminum nitrate nonahydrate in 40mL of water, and uniformly mixing to obtain solution A; dissolving 0.034g of sodium nitrate in 40mL of water containing 25% of formamide, and uniformly mixing to obtain solution B; dissolving 0.35g of sodium hydroxide in 35mL of water, and uniformly mixing to obtain solution C; slowly adding the solution A into the solution B under the stirring of water bath at 80 ℃, then dropwise adding the solution C, adjusting the pH to 9, mechanically stirring and reacting for 10min at room temperature, centrifuging for 10min by using a centrifuge with the rotation speed of 8000 plus 10000rpm/s, respectively washing the obtained precipitate for 2 times by using deionized water and absolute ethyl alcohol, drying for 6h in a vacuum drying oven at 60 ℃, and re-dispersing to water to obtain hydrotalcite nanosheet colloid, wherein the mass concentration of the hydrotalcite nanosheets in the colloid is 1 mg/mL.
2) Taking 10mL of the hydrotalcite nanosheet colloidal solution obtained in the step 1), dissolving 1mg of artemisinin in 1mL of polyethylene glycol aqueous solution with the mass concentration of 1%, dissolving 1mg of indocyanine green in 1mL of deionized water, respectively adding 400 mu L of artemisinin solution and 100 mu L of indocyanine green solution into 10mL of hydrotalcite nanosheet colloid under the inert gas Ar, stirring with magnetons for 12h in the dark, centrifuging, washing, separating, and then re-dispersing the precipitate into water to obtain the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material.
In the embodiment, the size of the obtained artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is 60-80 nm. The material is dispersed in water, and under the irradiation of a 808nm laser, the material has good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 4
Example 2 was repeated except that "200. mu.L of the artemisinin solution and 300. mu.L of the indocyanine green solution" in step 2) was changed to "300. mu.L of the artemisinin solution and 200. mu.L of the indocyanine green solution". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 50-70 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 5
Example 3 was repeated with the difference that "400. mu.L of artemisinin solution and 100. mu.L of indocyanine green solution in step 2) were" exchanged "for 100. mu.L of artemisinin solution and 400. mu.L of indocyanine green solution. And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 60-80 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 6
Example 1 is repeated, except that the "250 μ L of artemisinin solution and 250 μ L of indocyanine green solution" in step 2) are replaced by "500 μ L of artemisinin solution and 500 μ L of indocyanine green solution", and the rest conditions are not changed, so as to prepare the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material. Wherein the theoretical loading capacity of the drug molecules on the hydrotalcite nano-sheets is 10%. The size of the obtained composite material is 50-80 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 7
Example 6 is repeated, except that "1 mg of artemisinin" in step 2) is replaced by "2 mg of artemisinin", and "1 mg of indocyanine green" is replaced by "2 mg of indocyanine green", and the other conditions are not changed, so as to prepare the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material. Wherein the theoretical loading capacity of the drug molecules on the hydrotalcite nanosheets is 20%, the size of the obtained composite material is 70-90 nm, and the thickness is slightly increased. The material is dispersed in water, and under the irradiation of a 808nm laser, the material has good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 8
Example 7 is repeated, except that "500 μ L of artemisinin solution and 500 μ L of indocyanine green solution" in step 2) are replaced by "800 μ L of artemisinin solution and 200 μ L of indocyanine green solution", and the rest conditions are not changed, so as to prepare the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material. The size of the obtained composite material is 80-100 nm, and the thickness is slightly increased. The material is dispersed in water, and under the irradiation of a 808nm laser, the material has good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 9
Example 3 was repeated except that "1 mL of a 1% by mass aqueous solution of polyethylene glycol" in step 2) was replaced with "1 mL of a 1% by mass polyvinyl alcohol resin solution", and "12 h" was changed to "6 h". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 80-100 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 10
Example 3 was repeated except that "1 mL of a 1% by mass aqueous solution of polyethylene glycol" in step 2) was changed to "1 mL of a 1% by mass solution of polylactic acid" and "12 h" was changed to "6 h". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 70-90 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 11
Example 3 was repeated except that "1 mL of a 1% by mass aqueous solution of polyethylene glycol" in step 2) was changed to "1 mL of a 1% by mass chitosan solution", and "12 h" was changed to "6 h". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 80-100 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 12
Example 3 was repeated except that "1 mL of 1% by mass aqueous polyethylene glycol solution" in step 2) was changed to "1 mL of 1% by mass cellulose solution" and "12 h" was changed to "6 h". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 60-80 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 13
Example 3 was repeated except that "1 mL of an aqueous solution of polyethylene glycol having a mass concentration of 1% in step 2)" was changed to "1 mL of a solution of polyhydroxybutyrate having a mass concentration of 0.2%, and" 12h "was changed to" 6h ". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 80-100 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 14
Example 3 was repeated, except that "1 mL of a 1% by mass aqueous solution of polyethylene glycol" in step 2) was changed to "1 mL of a 0.5% by mass solution of polyglycolic acid", and "12 h" was changed to "6 h". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 80-100 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 15
Example 1 was repeated, with the difference that "magnesium nitrate hexahydrate" in step 1) was replaced by "ferrous nitrate". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 90-120 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 16
Example 15 was repeated, with the difference that "ferrous nitrate" in step 1) was replaced by "zinc nitrate". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 90-120 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 17
Example 1 was repeated, with the difference that "magnesium nitrate hexahydrate" in step 1) was changed to "cobalt nitrate" and "aluminum nitrate hexahydrate" was changed to "iron nitrate". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 70-100 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Example 18
Example 17 was repeated, with the difference that "magnesium nitrate hexahydrate" in step 1) was replaced by "nickel nitrate". And the rest conditions are unchanged, and the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material is prepared. The size of the obtained composite material is 80-100 nm, the composite material is dispersed in water, and under the irradiation of a 808nm laser, the material has a good photo-thermal conversion effect, can generate a large amount of singlet oxygen, can also generate a large amount of active oxygen species, and has an excellent chemical kinetics treatment effect; meanwhile, the material also has good performances of fluorescence imaging and photoacoustic imaging.
Comparative example 1
The preparation method is basically the same as that of the embodiment 1, except that indocyanine green is not added in the step 2), and other conditions are not changed, so that the obtained composite material is artemisinin/ultrathin hydrotalcite nanosheets; only has chemokinetic effect, no phototherapy effect and general treatment effect.
Comparative example 2
The preparation method is basically the same as that of the embodiment 1, except that no artemisinin is added in the step 2), and other conditions are unchanged, so that the obtained composite material is indocyanine green/ultrathin hydrotalcite nanosheet; only has phototherapy effect, no dynamic treatment effect and general treatment effect.
Comparative example 3
The preparation method is basically the same as that in the embodiment 1, except that the ultrathin hydrotalcite nanosheets are not added in the step 2), the other conditions are unchanged, and the obtained composite material is artemisinin and indocyanine green; the singlet oxygen generation efficiency is low, and the treatment effect is general.
Comparative example 4
The preparation method is basically the same as that in the example 1, except that the 'magneton stirring under dark conditions' in the step 2) is changed into 'magneton stirring under daily illumination', and the rest conditions are not changed, the indocyanine green is decomposed, so that the artemisinin and indocyanine green/ultrathin hydrotalcite nanosheet composite material can not be obtained.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention, and it will be obvious to those skilled in the art that other variations or modifications may be made on the basis of the above description, and all embodiments may not be exhaustive, and all obvious variations or modifications may be included within the scope of the present invention.
Claims (10)
1. An artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite, comprising: ultrathin hydrotalcite nanosheets, and artemisinin or polymer-protected artemisinin and indocyanine green loaded thereon.
2. The artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite of claim 1, wherein the polymer comprises polyvinyl alcohol resin, MW 16000-; polylactic acid, MW 30000-50000; chitosan, MW: 10000-50000; cellulose, MW 50000-100000; polyhydroxybutyrate, MW 10000-50000; polyethylene glycol, MW 400-; or polyglycolic acid, MW: 10000-.
3. The artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material of claim 1, wherein the amount of artemisinin and indocyanine green loaded on the ultrathin hydrotalcite nanosheets is 5-25%;
the mass ratio of the artemisinin to the indocyanine green is 0.25-4.
4. The artemisinin of claim 1&The indocyanine green/ultrathin hydrotalcite nanosheet composite material is characterized in that the ultrathin hydrotalcite nanosheet is 50-100nm in size, 1-2nm in thickness and layered double hydroxide, and the chemical composition of the ultrathin hydrotalcite nanosheet is represented as [ MⅡ 1-x MⅢ x(OH)2]An- z/n·yH2O；
Wherein M isⅡ、MⅢRespectively a positively charged divalent metal ion and a trivalent metal ion, MⅡIs Mg2+、Fe2+、Zn2+、Mn2+、Co2+One of (1), MⅢIs Al3+、Fe3+、Cr3+One of (1);
x is MⅡ/(MⅡ+MⅢ) The molar ratio of (a) is 1/3-1/4;
y is the amount of crystal water and ranges from 0 to 10;
An-is an interlayer anion, is NO3 -。
5. A preparation method of the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material as described in any one of claims 1 to 4, comprising the following steps:
1) uniformly mixing a metal nitrate solution and a sodium nitrate solution containing formamide, and adjusting the pH to 8-10 by using a sodium hydroxide solution; reacting for 1-60min at a certain temperature, centrifuging the obtained slurry, precipitating, washing, drying, and dissolving in deionized water to obtain an ultrathin hydrotalcite nanosheet colloidal solution;
2) sequentially adding an indocyanine green solution and an artemisinin solution or a polymer-protected artemisinin solution into the ultrathin hydrotalcite nanosheet colloidal solution obtained in the step 1), reacting in a dark place for 1-12h under inert gas, centrifuging the obtained slurry, precipitating, washing, and dispersing into water to obtain the artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material.
6. The method according to claim 5, wherein in step 1), the metal nitrate solution comprises a divalent metal nitrate and a trivalent metal nitrate;
the divalent metal nitrate is selected from one of magnesium nitrate, ferrous nitrate, zinc nitrate, manganese nitrate or cobalt nitrate, and the trivalent metal nitrate is selected from one of ferric nitrate, aluminum nitrate or chromium nitrate.
7. The preparation method according to claim 6, wherein the metal nitrate solution has a mass concentration of 1 to 2.5%, and the solvent is water;
in the formamide-containing sodium nitrate solution, the mass concentration of sodium nitrate is 0.05-0.15%, the mass concentration of formamide is 20-25%, and the solvent is water;
the mass concentration of the sodium hydroxide solution is 1-2%, and the solvent is water;
preferably, the molar ratio of the divalent metal nitrate, the trivalent metal nitrate and the sodium nitrate is (1-X): x: 2X, wherein X is 1/3-1/4.
8. The preparation method of claim 5, wherein the mass ratio of the polymer to the artemisinin is 2: 1-10: 1;
preferably, the polymer-protected artemisinin solution is prepared by the following steps:
firstly, preparing a polymer aqueous solution with a certain mass concentration, and then dispersing artemisinin in the polymer aqueous solution; wherein the mass concentration of the polymer is 0.1-2%, and the mass concentration of the artemisinin is 0.01-0.2%.
9. The preparation method according to claim 5, wherein the mass concentration of the indocyanine green solution is 0.01-0.2%, and the solvent is water;
preferably, the inert gas includes one or more of helium, neon and argon;
preferably, the washed solvent in step 1) comprises deionized water and absolute ethanol; the washed solvent in step 2) comprises deionized water.
10. The artemisinin & indocyanine green/ultrathin hydrotalcite nanosheet composite material of any one of claims 1 to 4 for use in tumor therapy.
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