CN109045298A - A kind of preparation method of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal- - Google Patents
A kind of preparation method of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal- Download PDFInfo
- Publication number
- CN109045298A CN109045298A CN201811000805.0A CN201811000805A CN109045298A CN 109045298 A CN109045298 A CN 109045298A CN 201811000805 A CN201811000805 A CN 201811000805A CN 109045298 A CN109045298 A CN 109045298A
- Authority
- CN
- China
- Prior art keywords
- fluorinated graphene
- folic acid
- hypericin
- solution
- targeting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229920000642 polymer Polymers 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000002114 nanocomposite Substances 0.000 title claims abstract description 12
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims abstract description 48
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims abstract description 35
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229960000304 folic acid Drugs 0.000 claims abstract description 23
- 235000019152 folic acid Nutrition 0.000 claims abstract description 23
- 239000011724 folic acid Substances 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 20
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910021389 graphene Inorganic materials 0.000 claims abstract description 14
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical class CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims abstract description 7
- BTXNYTINYBABQR-UHFFFAOYSA-N hypericin Chemical compound C12=C(O)C=C(O)C(C(C=3C(O)=CC(C)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 BTXNYTINYBABQR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229940005608 hypericin Drugs 0.000 claims abstract description 7
- PHOKTTKFQUYZPI-UHFFFAOYSA-N hypericin Natural products Cc1cc(O)c2c3C(=O)C(=Cc4c(O)c5c(O)cc(O)c6c7C(=O)C(=Cc8c(C)c1c2c(c78)c(c34)c56)O)O PHOKTTKFQUYZPI-UHFFFAOYSA-N 0.000 claims abstract description 7
- SSKVDVBQSWQEGJ-UHFFFAOYSA-N pseudohypericin Natural products C12=C(O)C=C(O)C(C(C=3C(O)=CC(O)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 SSKVDVBQSWQEGJ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 238000000502 dialysis Methods 0.000 claims description 18
- 239000006185 dispersion Substances 0.000 claims description 16
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 15
- 238000004108 freeze drying Methods 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000008367 deionised water Substances 0.000 claims description 12
- 229910021641 deionized water Inorganic materials 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical class [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 11
- 125000003929 folic acid group Chemical group 0.000 claims description 11
- 238000002604 ultrasonography Methods 0.000 claims description 11
- 241000446313 Lamella Species 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 230000010355 oscillation Effects 0.000 claims description 8
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 7
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 7
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 7
- 238000002242 deionisation method Methods 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- 239000013049 sediment Substances 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000012545 processing Methods 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 3
- 239000004567 concrete Substances 0.000 claims description 2
- 230000003534 oscillatory effect Effects 0.000 claims description 2
- 238000009210 therapy by ultrasound Methods 0.000 claims description 2
- 239000002131 composite material Substances 0.000 claims 1
- 239000002086 nanomaterial Substances 0.000 abstract description 14
- 206010028980 Neoplasm Diseases 0.000 abstract description 13
- 201000011510 cancer Diseases 0.000 abstract description 8
- 230000002195 synergetic effect Effects 0.000 abstract description 6
- 238000002512 chemotherapy Methods 0.000 abstract description 5
- 238000000015 thermotherapy Methods 0.000 abstract description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 abstract description 2
- 229910000040 hydrogen fluoride Inorganic materials 0.000 abstract description 2
- 238000002626 targeted therapy Methods 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000003643 water by type Substances 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000012377 drug delivery Methods 0.000 description 3
- 238000003682 fluorination reaction Methods 0.000 description 3
- -1 graphite alkene Chemical class 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003504 photosensitizing agent Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- OUHVPTUNAKUCJX-UHFFFAOYSA-N N1=CC=CC=C1.CN(C=1C=CNC1)C Chemical compound N1=CC=CC=C1.CN(C=1C=CNC1)C OUHVPTUNAKUCJX-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000005408 paramagnetism Effects 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- 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
- 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/52—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/545—Heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to pharmaceutical fields, disclose a kind of preparation method of photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal-.The present invention first passes through graphene oxide and hydrogen fluoride synthesis fluorinated graphene；Then fluorinated graphene is reacted to obtain folic acid-fluorinated graphene with folic acid, 1- ethyl-(3- dimethylamino-propyl) carbodiimides, nitrogen-HOSu NHS；Finally react folic acid-fluorinated graphene and hypericin, 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride and 4-dimethylaminopyridine to obtain finished product.The polymer nano material of this method preparation can be achieved to targeted therapy, and the synergistic effect of tumor thermotherapy and chemotherapy increases the stability of polymer nano material, be expected to be used for cancer cell treatment；This method will not make a significant impact cell in the experimentation in later period simultaneously.
Description
Technical field
The present invention relates to pharmaceutical field more particularly to a kind of photodynamic hypericin-folic acid-fluorination stones of targeting-photo-thermal-
The preparation method of black alkene polymer nanocomposite.
Background technique
Cancer (malignant tumour) is one of the refractory disease for seriously endangering human health, every year disease incidence all with higher
And the death rate.Therefore, tumour is formed and the research for the treatment of method, oneself current warp becomes the research emphasis and heat of researcher
Point.In recent years, the biomedical treatment for being combined into cancer with nanotechnology brings new opportunities.With unique optics, magnetic
The Nano medication of the physicochemical properties such as, electricity and acoustics brings new approaches for the prevention of major disease, diagnosing and treating.Its
In, polymer nano material has excellent biocompatibility and degradability, programmable size and surface property, higher load
Dose and drug delivery efficiency, good cyclical stability and EPR effect are realized high to improve the bioavilability of drug
The drug targeting of effect and control release.Therefore, nowadays polymer nano material is widely used in drug delivery system.
How extensive use with polymer nano material as pharmaceutical carrier in terms of biological medicine, allow polymer nano
Rice material has both the synergistic effect of targeting, tumor thermotherapy and chemotherapy simultaneously, improves it in drug targeting and metabolic stability side
The problems such as deficiency in face, has become focus of attention.At the same time, various multifunctional polymer nano materials are as a kind of drug
Delivery vehicles, will not only be such that the toxicity of drug minimizes, and also improve its stability and the retention time at required position.Cause
This, it is extremely urgent to study polymer nano material that is a kind of while having both targeting, tumor thermotherapy and chemotherapy synergistic effect.
Summary of the invention
In order to solve the above-mentioned technical problems, the present invention provides a kind of photodynamic hypericin-folic acid-of targeting-photo-thermal-
The preparation method of fluorinated graphene polymer nanocomposites.The present invention passes through graphene oxide dispersion and hydrogen fluoride first
Hydro-thermal reaction synthesize fluorinated graphene, and it is purified；Then pass through fluorinated graphene and folic acid, 1- ethyl-(3- bis-
Methylaminopropyl) carbodiimides, nitrogen-HOSu NHS react to obtain folic acid-fluorinated graphene；Finally by folic acid-
Fluorinated graphene and hypericin, 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride and 4- dimethylamino pyrrole
Pyridine reaction obtains hypericin-folic acid-fluorinated graphene polymer nano material overnight.The polymer nanocomposite material of this method preparation
Expect that targeted therapy can be achieved, the synergistic effect of tumor thermotherapy and chemotherapy increases the stability of polymer nano material, is expected to be used for
Cancer cell treatment；This method will not make a significant impact cell in the experimentation in later period simultaneously, experimental implementation process letter
It is single, nontoxic, harmless, environmentally protective.
The specific technical proposal of the invention is: a kind of targeting-photo-thermal-light power synergistic treatment hypericin-folic acid-fluorine
The preparation method of graphite alkene polymer nanocomposite, in terms of mL and g, comprising the following steps:
1) graphene oxide dispersion and 0.5 ~ 0.75 mL concentration for being 1-3mg/mL by 40 ~ 60 mL concentration by ultrasonic treatment
1 ~ 2 min is mixed for the hydrofluoric acid of 35-45wt%, obtains mixed liquor, it is spare.
2) mixed liquor for obtaining step 1) is transferred in polytetrafluoroethyllining lining autoclave, and is protected at 180 ~ 200 DEG C
30 ~ 40 h are held, it is spare then to autoclave cooled to room temperature.
In step 2, graphene oxide is modified using fluorination reaction kettle, obtains fluorinated graphene, carries fluorescence
Effect, photo-thermal effect significantly increase.
3) product obtained using micro-pore-film filtration step 2, by washing repeatedly, during centrifugal filtration makes solution finally and is in
Property, it is then freeze-dried to obtain fluorinated graphene, it is spare.
4) fluorinated graphene is taken, deionized water, 1 ~ 2 h of sonic oscillation under condition of ice bath, the stripping of fluorographite lamella is added
It falls, obtains the dispersion liquid of brown color, centrifugation removal sediment obtains fluorographite aqueous solution.
In step 4), handled by sonic oscillation etc. to obtain evenly dispersed fluorinated graphene.
5) it is 2 ~ 3 d that dialyse in 8000 ~ 14000 bag filter in molecular cut off by fluorographite aqueous solution, obtains
Fluorinated graphene dispersion liquid after purification, the fluorinated graphene that freeze-dried processing is purified are spare.
In step 5), extra water-soluble substances are removed using dialysis operation.
6) 100 ~ 150 mg fluorinated graphenes are weighed, and are dispersed in 80-120 mL deionized water, ultrasonic disperse is uniform,
Then 5 ~ 7 g sodium hydroxides, 5 ~ 7 g sodium hypochlorite are added, 2 ~ 3 h of ultra sonic bath converts the hydroxyl on fluorinated graphene lamella
For carboxyl；After fully reacting, is neutralized and rinsed repeatedly, centrifugal treating with dilute hydrochloric acid, collected the dark solution on upper layer, then spend
Ionized water dialysis 40-50 h, removes unreacted water-soluble substances.
In step 6), by fluorinated graphene and sodium hydroxide, sodium hypochlorite reaction, turn the hydroxyl on fluorinated graphene
Carboxyl is turned to, is conducive to next react with the amino on folic acid；It is to guarantee sample always using dilute hydrochloric acid washing
For neutrality；Dialysis treatment is concentration and the higher solution of purity in order to obtain.
7) 0.5 ~ 0.8 g folic acid is added into the solution that step 6) obtains, ultrasonic disperse is uniform, addition 125 while stirring ~
1- ethyl-(3- dimethylamino-propyl) carbodiimides and 182.5 ~ 184.5 mg nitrogen-HOSu NHS of 127 mg,
2 ~ 3 h are ultrasonically treated, the sodium bicarbonate solution dialysis treatment of pH=7-9 is then used, every 3-5 h changes a water, after 40-50 h
Dialysis is completed, dark solution is obtained.
In step 7), 1- ethyl-(3- dimethylamino-propyl) carbodiimides and nitrogen-HOSu NHS conduct
Crosslinking agent acts on as activating fluorinated graphene, reacts it sufficiently with folic acid, by the way that folic acid is connected to polymer particles table
Face increases its associativity with receptor, and the polymer particles of carrying medicament is made largely to be gathered in subject cell surface；Use carbonic acid
Hydrogen sodium is to guarantee that solution is in neutrallty condition as dialyzate.
8) it using the moisture in rotary evaporation removal dark solution, is washed repeatedly with acetone, it is then true at 40 ~ 50 DEG C
Sky is dry, obtains the fluorinated graphene of modified with folic acid, spare.
In step 8), being washed repeatedly using acetone is to be close to synthetic environment to reduce solution zeta current potential.
9) fluorinated graphene for taking 64.8 ~ 66.8 mg modified with folic acid is scattered in 40-60 mL deionization, then
6.05 ~ 6.25 mg hypericins, 2.76 ~ 2.96 mg 1- ethyls-(3- dimethylaminopropyl) carbodiimides hydrochloric acid are added
Salt and 0.30 ~ 0.32 mg 4-dimethylaminopyridine are stirred to react overnight.
In step 9), 1- ethyl-(3- dimethylamino joined in the reaction of folic acid-fluorinated graphene and hypericin
Base propyl) carbodiimide hydrochloride and 4-dimethylaminopyridine, wherein 1- ethyl-(3- dimethylaminopropyl) carbonization two is sub-
Amine hydrochlorate is as polypeptide condensing agent and crosslinking agent, it can be achieved that quickly polypeptide condensation reaction；4-dimethylaminopyridine is as a kind of
Efficient catalyst, catalytic capability with higher, hence it is evident that improve yield.
10) solution that step 9) obtains is filtered, then freeze-dried operation using super filter tube, obtains hypericin-leaf
Acid-fluorinated graphene polymer nano-particle.
Preferably, in step 4), oscillatory process are as follows: ultrasonic grinder is used, to mixture under the power of 500 W
Carry out 1 h of sonic oscillation；Centrifugal process are as follows: use high-speed refrigerated centrifuge, be centrifuged 15 under conditions of 12000 ~ 13000 r/min
~20 min。
Preferably, in step 6), centrifugal process are as follows: high-speed refrigerated centrifuge is used, 8000 ~ 10000 r/min's
Under the conditions of be centrifuged 15 ~ 20 min.
Preferably, the resulting solution of step 9) is pre-chilled before use, being placed in 3 ~ 5 DEG C of environment.
Preferably, in step 10), super filter tube filtering, freeze-drying concrete operations are as follows: pass through 100 kDa screen pipes
It is centrifuged solution and then repeatedly washs filtrate with deionized water to remove excessive hypericin, finally carry out freeze-drying process.
It is compared with the prior art, the beneficial effects of the present invention are:
1. being modified processing in step 2 to graphene oxide by fluorination reaction kettle and obtaining fluorinated graphene, be fluorinated stone
Black alkene has the characteristics that the paramagnetism that surface energy is low, hydrophobicity is strong, band gap is wide, stable, carries fluorescent effect, and photo-thermal effect is aobvious
Write enhancing.
2. being purified by processing such as ultrasound, centrifugation, dialysis to fluorinated graphene, uniformly being divided in step 5)
Scattered small size fluorinated graphene.
3. in step 6), by fluorinated graphene and sodium hydroxide, sodium hypochlorite reacts makes on fluorinated graphene
Hydroxyl be converted into carboxyl, guarantee that it is sufficiently reacted with folic acid.
4., by the way that folic acid is connected to surface of polymer material, increasing its associativity with receptor in step 7), making
The polymer particles of carrying medicament are largely gathered in subject cell surface, thus increase the drug concentration of site of action, reduction pair
The toxic side effect of normal cell.
5. the solution of preparation being placed in 3 ~ 5 DEG C of environment and being pre-chilled, avoid the shadow to subsequent experimental in step 9)
It rings, improves the success rate of experiment.
6. a kind of polymer will can be obtained after the fluorographite alkene reaction of hypericin and modified with folic acid in step 10)
Nano material, wherein hypericin has photo-activity as a kind of photosensitizer, can be thin in tissue and cell by destroying
Born of the same parents' device finally causes the death of cancer cell, achievees the purpose that treating cancer.
7. efficient tumor thermotherapy and chemotherapy synergistic effect can be realized by preparing polymer nano material in invention,
Increase the stability of drug, realize active targeting, increases the binding ability with receptor, cancer cell is controlled to greatly promote
Therapeutic effect.
8. it is non-toxic by constructing a kind of safety in invention, and it is capable of the pharmaceutical carrier of efficient transportation photosensitizer,
It can be improved the stability of drug, convenient for storage.
Specific embodiment
The present invention will be further described with reference to the examples below.
Embodiment 1:
1) by be ultrasonically treated by 40 mL concentration be 2mg/mL graphene oxide dispersion and 0.5 mL concentration be 40wt%
Hydrofluoric acid mix 1 min, it is spare；
2) mixture for obtaining step 1) is transferred in 50 mL polytetrafluoroethyllining lining autoclaves, and keeps 30 at 180 DEG C
H, it is spare then to autoclave cooled to room temperature；
3) product obtained using micro-pore-film filtration step 2, by washing repeatedly, centrifugal filtration is in neutrality solution finally, so
Fluorinated graphene is obtained by freeze-drying afterwards, it is spare；
4) 50 mL deionized waters, under condition of ice bath, the power of 500 W are added in the fluorinated graphene for taking appropriate step 3) to obtain
Under to mixture carry out 1 h of sonic oscillation, fluorographite lamella peel off, the dispersion liquid of brown color is obtained, 12000 r/min's
Under the conditions of be centrifuged 15 min to remove sediment to get to fluorographite aqueous solution；
5) fluorographite aqueous solution that step 4) obtains is dialysed 2 d in the bag filter that molecular cut off is 8000, is obtained
Filtrate be fluorinated graphene dispersion liquid after purification, obtain fluorinated graphene powder by freeze-drying process, it is spare；
6) 100 mg fluorinated graphenes are weighed, and are dispersed in 100 mL deionized waters, ultrasound makes it be uniformly dispersed, and is then added
The hydroxyl on fluorinated graphene lamella is converted carboxyl by 5 g sodium hydroxides, 5 g sodium hypochlorite, 2 h of ultra sonic bath.Fully reacting
Afterwards, it is neutralized and is rinsed repeatedly, 15 min of centrifugal treating under conditions of 8000 r/min with dilute hydrochloric acid, the black for collecting upper layer is molten
Then liquid uses 48 h of deionized water dialysis, removes unreacted water-soluble substances；
7) 0.5 g folic acid is added into the solution that step 6) obtains, ultrasound makes it be uniformly dispersed, and adds while stirring into mixture
Enter 125 mg 1- ethyls-(3- dimethylamino-propyl) carbodiimides and 182.5 mg nitrogen-HOSu NHS, at ultrasound
2 h are managed, then carry out dialysis treatment using the sodium bicarbonate solution of PH=8, every 4 h changes a water, completes dialysis after 48 h, obtain
To dark solution；
8) moisture in the solution that step 7) obtains is removed using rotary evaporation, is washed repeatedly with acetone, and is placed on 40 DEG C
It is dry in vacuum oven, the fluorinated graphene of modified with folic acid is obtained, folic acid-fluorinated graphene is denoted as, it is spare；
9) fluorinated graphene for the modified with folic acid for taking 64.8 mg step 8) to obtain is dispersed in 50 mL deionizations, then
6.05 mg hypericins, 2.76 mg 1- ethyls-(3- dimethylaminopropyl) carbodiimide hydrochloride and 0.30 are added
Mg 4-dimethylaminopyridine is stirred to react overnight, and is placed in 3 DEG C of environment and is pre-chilled；
10) solution for obtaining step 9) is filtered using 100 kDa super filter tubes, then repeatedly washs filtrate with deionized water, then
By the operation such as freeze-drying, hypericin-folic acid-fluorinated graphene polymer nano material can be obtained.
Embodiment 2:
1) by be ultrasonically treated by 50 mL concentration be 2mg/mL graphene oxide dispersion and 0.6mL concentration be 40wt%
Hydrofluoric acid mix 2 min, it is spare；
2) mixture for obtaining step 1) is transferred in 50 mL polytetrafluoroethyllining lining autoclaves, and keeps 35 at 190 DEG C
H, it is spare then to autoclave cooled to room temperature；
3) product obtained using micro-pore-film filtration step 2, by washing repeatedly, centrifugal filtration is in neutrality solution finally, so
Fluorinated graphene is obtained by freeze-drying afterwards, it is spare；
4) 50 mL deionized waters, under condition of ice bath, the power of 500 W are added in the fluorinated graphene for taking appropriate step 3) to obtain
Under to mixture carry out 1.5 h of sonic oscillation, fluorographite lamella peel off, the dispersion liquid of brown color is obtained, in 12000 r/min
Under conditions of be centrifuged 20 min to remove sediment to get to fluorographite aqueous solution；
5) fluorographite aqueous solution that step 4) obtains is dialysed 2 d in the bag filter that molecular cut off is 10000, is obtained
Filtrate be fluorinated graphene dispersion liquid after purification, obtain fluorinated graphene powder by freeze-drying process, it is spare；
6) 125 mg fluorinated graphenes are weighed, and are dispersed in 100 mL deionized waters, ultrasound makes it be uniformly dispersed, and is then added
The hydroxyl on fluorinated graphene lamella is converted carboxyl by 6 g sodium hydroxides, 6 g sodium hypochlorite, 2 h of ultra sonic bath.Fully reacting
Afterwards, it is neutralized and is rinsed repeatedly, 15 min of centrifugal treating under conditions of 9000 r/min with dilute hydrochloric acid, the black for collecting upper layer is molten
Then liquid uses 48 h of deionized water dialysis, removes unreacted water-soluble substances；
7) 0.7 g folic acid is added into the solution that step 6) obtains, ultrasound makes it be uniformly dispersed, and adds while stirring into mixture
Enter 126 mg 1- ethyls-(3- dimethylamino-propyl) carbodiimides and 183.5 mg nitrogen-HOSu NHS, at ultrasound
2 h are managed, then carry out dialysis treatment using the sodium bicarbonate solution of PH=8, every 4 h changes a water, completes dialysis after 48 h, obtain
To dark solution；
8) moisture in the solution that step 7) obtains is removed using rotary evaporation, is washed repeatedly with acetone, and is placed on 40 ~ 50
It is dry in DEG C vacuum oven, the fluorinated graphene of modified with folic acid is obtained, folic acid-fluorinated graphene is denoted as, it is spare；
9) fluorinated graphene for the modified with folic acid for taking 65.8 mg step 8) to obtain is dispersed in 50 mL deionizations, then
6.15 mg hypericins, 2.86 mg 1- ethyls-(3- dimethylaminopropyl) carbodiimide hydrochloride and 0.31 are added
Mg 4-dimethylaminopyridine is stirred to react overnight, and is placed in 4 DEG C of environment and is pre-chilled；
10) solution for obtaining step 9) is filtered using 100 kDa super filter tubes, then repeatedly washs filtrate with deionized water, then
By the operation such as freeze-drying, hypericin-folic acid-fluorinated graphene polymer nano material can be obtained.
Embodiment 3:
1) by be ultrasonically treated by 60 mL concentration be 2mg/mL graphene oxide dispersion and 0.75 mL concentration be
The hydrofluoric acid of 40wt% mixes 1 ~ 2 min, spare；
2) mixture for obtaining step 1) is transferred in 50 mL polytetrafluoroethyllining lining autoclaves, and keeps 40 at 200 DEG C
H, it is spare then to autoclave cooled to room temperature；
3) product obtained using micro-pore-film filtration step 2, by washing repeatedly, centrifugal filtration is in neutrality solution finally, so
Fluorinated graphene is obtained by freeze-drying afterwards, it is spare；
4) 50 mL deionized waters, under condition of ice bath, the power of 500 W are added in the fluorinated graphene for taking appropriate step 3) to obtain
Under to mixture carry out 2 h of sonic oscillation, fluorographite lamella peel off, the dispersion liquid of brown color is obtained, 13000 r/min's
Under the conditions of be centrifuged 20 min to remove sediment to get to fluorographite aqueous solution；
5) fluorographite aqueous solution that step 4) obtains is dialysed 3 d in the bag filter that molecular cut off is 14000, is obtained
Filtrate be fluorinated graphene dispersion liquid after purification, obtain fluorinated graphene powder by freeze-drying process, it is spare；
6) 150 mg fluorinated graphenes are weighed, and are dispersed in 100 mL deionized waters, ultrasound makes it be uniformly dispersed, and is then added
The hydroxyl on fluorinated graphene lamella is converted carboxyl by 7 g sodium hydroxides, 7 g sodium hypochlorite, 3 h of ultra sonic bath.Fully reacting
Afterwards, it is neutralized with dilute hydrochloric acid and is rinsed repeatedly, 20 min of centrifugal treating under conditions of 10000 r/min collects the black on upper layer
Then solution uses 48 h of deionized water dialysis, removes unreacted water-soluble substances；
7) 0.8 g folic acid is added into the solution that step 6) obtains, ultrasound makes it be uniformly dispersed, and adds while stirring into mixture
Enter 127 mg 1- ethyls-(3- dimethylamino-propyl) carbodiimides and 184.5 mg nitrogen-HOSu NHS, at ultrasound
3 h are managed, then carry out dialysis treatment using the sodium bicarbonate solution of PH=8, every 4 h changes a water, completes dialysis after 48 h, obtain
To dark solution；
8) moisture in the solution that step 7) obtains is removed using rotary evaporation, is washed repeatedly with acetone, and is placed on 50 DEG C
It is dry in vacuum oven, the fluorinated graphene of modified with folic acid is obtained, folic acid-fluorinated graphene is denoted as, it is spare；
9) fluorinated graphene for the modified with folic acid for taking 66.8 mg step 8) to obtain is dispersed in 50 mL deionizations, then
6.25 mg hypericins, 2.96 mg 1- ethyls-(3- dimethylaminopropyl) carbodiimide hydrochloride and 0.32 are added
Mg 4-dimethylaminopyridine is stirred to react overnight, and is placed in 3 ~ 5 DEG C of environment and is pre-chilled；
10) solution for obtaining step 9) is filtered using 100 kDa super filter tubes, then repeatedly washs filtrate with deionized water, then
By the operation such as freeze-drying, hypericin-folic acid-fluorinated graphene polymer nano material can be obtained.
Raw materials used in the present invention, equipment is unless otherwise noted the common raw material, equipment of this field；In the present invention
Method therefor is unless otherwise noted the conventional method of this field.
The above is only presently preferred embodiments of the present invention, is not intended to limit the invention in any way, it is all according to the present invention
Technical spirit any simple modification, change and equivalent transformation to the above embodiments, still fall within the technology of the present invention side
The protection scope of case.
Claims (5)
1. a kind of preparation of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal-
Method, which is characterized in that in terms of mL and g, comprising the following steps:
1) graphene oxide dispersion and 0.5 ~ 0.75 mL concentration for being 1-3mg/mL by 40 ~ 60 mL concentration by ultrasonic treatment
1 ~ 2 min is mixed for the hydrofluoric acid of 35-45wt%, obtains mixed liquor, it is spare；
2) mixed liquor for obtaining step 1) is transferred in polytetrafluoroethyllining lining autoclave, and at 180 ~ 200 DEG C keep 30 ~
40 h, it is spare then to autoclave cooled to room temperature；
3) product obtained using micro-pore-film filtration step 2, by washing repeatedly, centrifugal filtration is in neutrality solution finally, so
Fluorinated graphene is obtained by freeze-drying, it is spare；
4) fluorinated graphene is taken, deionized water, 1 ~ 2 h of sonic oscillation under condition of ice bath is added, fluorographite lamella is peeled off, obtained
The dispersion liquid of brown color is obtained, centrifugation removal sediment obtains fluorographite aqueous solution；
5) it is 2 ~ 3 d that dialyse in 8000 ~ 14000 bag filter in molecular cut off by fluorographite aqueous solution, is purified
Fluorinated graphene dispersion liquid afterwards, the fluorinated graphene that freeze-dried processing is purified are spare；
6) 100 ~ 150 mg fluorinated graphenes are weighed, and are dispersed in 80-120 mL deionized water, ultrasonic disperse is uniform, then
5 ~ 7 g sodium hydroxides, 5 ~ 7 g sodium hypochlorite are added, 2 ~ 3 h of ultra sonic bath makes the hydroxyl on fluorinated graphene lamella be converted into carboxylic
Base；After fully reacting, is neutralized and rinsed repeatedly, centrifugal treating with dilute hydrochloric acid, collected the dark solution on upper layer, then use deionization
Water dialysis 40-50 h, removes unreacted water-soluble substances；
7) 0.5 ~ 0.8 g folic acid is added into the solution that step 6) obtains, ultrasonic disperse is uniform, and 125 ~ 127 are added while stirring
1- ethyl-(3- dimethylamino-propyl) carbodiimides and 182.5 ~ 184.5 mg nitrogen-HOSu NHS of mg, ultrasound
2 ~ 3 h are handled, the sodium bicarbonate solution dialysis treatment of pH=7-9 is then used, every 3-5 h changes a water, completes after 40-50 h
Dialysis, obtains dark solution；
8) it using the moisture in rotary evaporation removal dark solution, is washed repeatedly with acetone, then vacuum is dry at 40 ~ 50 DEG C
It is dry, the fluorinated graphene of modified with folic acid is obtained, it is spare；
9) fluorinated graphene for taking 64.8 ~ 66.8 mg modified with folic acid is scattered in 40-60 mL deionization, is then added
6.05 ~ 6.25 mg hypericins, 2.76 ~ 2.96 mg 1- ethyls-(3- dimethylaminopropyl) carbodiimide hydrochloride and
0.30 ~ 0.32 mg 4-dimethylaminopyridine is stirred to react overnight；
10) solution that step 9) obtains is filtered, then freeze-dried operation using super filter tube, obtains finished product.
2. a kind of photodynamic hypericin-folic acid-fluorinated graphene polymer nano of targeting-photo-thermal-as described in claim 1
The preparation method of nano composite material, which is characterized in that in step 4), oscillatory process are as follows: ultrasonic grinder is used, in 500 W
Power under to mixture carry out 1 h of sonic oscillation；Centrifugal process are as follows: use high-speed refrigerated centrifuge, 12000 ~ 13000 r/
15 ~ 20 min are centrifuged under conditions of min.
3. a kind of photodynamic hypericin-folic acid-fluorinated graphene polymer nano of targeting-photo-thermal-as described in claim 1
The preparation method of nano composite material, which is characterized in that in step 6), centrifugal process are as follows: high-speed refrigerated centrifuge is used, 8000
15 ~ 20 min are centrifuged under conditions of ~ 10000 r/min.
4. a kind of photodynamic hypericin-folic acid-fluorinated graphene polymer nano of targeting-photo-thermal-as described in claim 1
The preparation method of nano composite material, which is characterized in that the resulting solution of step 9) is before use, be placed in 3 ~ 5 DEG C of environment pre-
It is cold.
5. the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposite of a kind of targeting-photo-thermal-described in claim 1
The preparation method of composite material, which is characterized in that in step 10), super filter tube filtering, freeze-drying concrete operations are as follows: pass through
100 kDa screen pipes are centrifuged solution and then repeatedly wash filtrate with deionized water to remove excessive hypericin, finally carry out
Freeze-drying process.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811000805.0A CN109045298A (en) | 2018-08-30 | 2018-08-30 | A kind of preparation method of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal- |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811000805.0A CN109045298A (en) | 2018-08-30 | 2018-08-30 | A kind of preparation method of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal- |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109045298A true CN109045298A (en) | 2018-12-21 |
Family
ID=64757764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811000805.0A Pending CN109045298A (en) | 2018-08-30 | 2018-08-30 | A kind of preparation method of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal- |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109045298A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110302378A (en) * | 2019-07-04 | 2019-10-08 | 浙江理工大学 | A kind of preparation method of the targeting photo-thermal nanocomposite based on graphene oxide |
| CN110484240A (en) * | 2019-09-04 | 2019-11-22 | 浙江理工大学 | A kind of preparation method of the dilute quantum dot of hyaluronic acid decorated fluorographite for biological in-vivo imaging |
| CN114432264A (en) * | 2021-12-31 | 2022-05-06 | 浙江大学 | Composite nano material based on ferrocene and hypericin, preparation method and application |
| CN116041168A (en) * | 2023-04-03 | 2023-05-02 | 中国农业大学 | Method for processing hypericin, hypericin carbon dot obtained by method and application of hypericin carbon dot |
-
2018
- 2018-08-30 CN CN201811000805.0A patent/CN109045298A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110302378A (en) * | 2019-07-04 | 2019-10-08 | 浙江理工大学 | A kind of preparation method of the targeting photo-thermal nanocomposite based on graphene oxide |
| CN110484240A (en) * | 2019-09-04 | 2019-11-22 | 浙江理工大学 | A kind of preparation method of the dilute quantum dot of hyaluronic acid decorated fluorographite for biological in-vivo imaging |
| CN114432264A (en) * | 2021-12-31 | 2022-05-06 | 浙江大学 | Composite nano material based on ferrocene and hypericin, preparation method and application |
| CN114432264B (en) * | 2021-12-31 | 2022-10-14 | 浙江大学 | Composite nano material based on ferrocene and hypericin, preparation method and application |
| CN116041168A (en) * | 2023-04-03 | 2023-05-02 | 中国农业大学 | Method for processing hypericin, hypericin carbon dot obtained by method and application of hypericin carbon dot |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109045298A (en) | A kind of preparation method of the photodynamic hypericin-folic acid-fluorinated graphene polymer nanocomposites of targeting-photo-thermal- | |
| CN109125727A (en) | A kind of preparation method of the nanocomposite based on poly-dopamine@graphene targeting-photo-thermal-light power synergistic treatment | |
| Thakur et al. | Synthesis and biomedical applications of nanoceria, a redox active nanoparticle | |
| CN106139144B (en) | A kind of hyaluronic acid decorated gold-Nano carbon balls and the preparation method and application thereof with synergistic antitumor characteristic | |
| Sivakumar et al. | Synthesis of silver nanoparticles using Lantana camara fruit extract and its effect on pathogens | |
| WO2004087577A1 (en) | Surface-modified titanium dioxide fine particles and dispersion comprising the same, and method for producing the same | |
| JP5577329B2 (en) | pH-sensitive metal nanoparticles and method for producing the same | |
| He et al. | An injectable silk fibroin nanofiber hydrogel hybrid system for tumor upconversion luminescence imaging and photothermal therapy | |
| CN104530263A (en) | Preparation method of gallic acid-bagasse xylan ester | |
| CN105031671A (en) | Prussian blue-based intelligent pH-triggered MRI drug release-monitoring synergetic nanometer diagnosis and treatment agent and preparation method thereof | |
| CN108785275A (en) | A kind of preparation method of the targeting being embedded with anticancer drug-optothermal polymerization object particle | |
| CN103936883A (en) | Mercapto-containing chitosan derivative, compound nano particle and preparation method | |
| Eivazzadeh-Keihan et al. | Biological investigation of a novel nanocomposite based on functionalized graphene oxide nanosheets with pectin, silk fibroin and zinc chromite nanoparticles | |
| Zhang et al. | Sonoactivated cascade Fenton reaction enhanced by synergistic modulation of electron–hole separation for improved tumor therapy | |
| JP2009073784A (en) | Titanium oxide composite particle, its dispersion and method for producing them | |
| CN108610460B (en) | Active oxygen stimulation response type nano gel drug carrier and preparation method and application thereof | |
| CN106215196A (en) | The preparation method of carbon/calcium phosphate/ferroso-ferric oxide composite construction nanoparticle | |
| CN109303917A (en) | It is a kind of for treating the preparation and preparation method thereof of skin neoplasin and neoplasm | |
| JP2005289660A (en) | Surface-modified titanium dioxide particulate and dispersion thereof and method for manufacturing the same | |
| CN115645371A (en) | Self-generated active oxygen nanoparticles for precise non-invasive colon cancer dynamic immunotherapy and preparation method and application thereof | |
| CN111701030B (en) | Preparation method of active targeting zirconium dioxide nanoparticles with defect of acoustic power effect | |
| CN110585442A (en) | Preparation method of hypericin nano composite material taking hyaluronic acid modified fluorinated graphene as carrier | |
| CN110302378A (en) | A kind of preparation method of the targeting photo-thermal nanocomposite based on graphene oxide | |
| Xu et al. | Precise phase adjustment and antibacterial property of copper sulfide particles in confined mesoporous silica nanoreactor | |
| CN110404069A (en) | A kind of nanocomposite based on poly-dopamine@MOF-Al complex carries targeting-photo-thermal-light power synergistic treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181221 |