CN116602988A - Application of selenocarbon spot in preparation of iron death inhibiting medicine or acute nephritis treating medicine - Google Patents
Application of selenocarbon spot in preparation of iron death inhibiting medicine or acute nephritis treating medicine Download PDFInfo
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- CN116602988A CN116602988A CN202310350502.6A CN202310350502A CN116602988A CN 116602988 A CN116602988 A CN 116602988A CN 202310350502 A CN202310350502 A CN 202310350502A CN 116602988 A CN116602988 A CN 116602988A
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- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 title claims abstract description 92
- 230000034994 death Effects 0.000 title claims abstract description 46
- 229910052742 iron Inorganic materials 0.000 title claims abstract description 46
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 14
- 201000008383 nephritis Diseases 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 14
- TXJZRSRTYPUYRW-NQIIRXRSSA-N methyl (1s,3r)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2C(=O)CCl)C(=O)OC)=CC=C(C(=O)OC)C=C1 TXJZRSRTYPUYRW-NQIIRXRSSA-N 0.000 claims abstract description 26
- 229940045835 RSL3 Drugs 0.000 claims abstract description 23
- BKQFRNYHFIQEKN-UHFFFAOYSA-N erastin Chemical compound CCOC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1C(C)N1CCN(C(=O)COC=2C=CC(Cl)=CC=2)CC1 BKQFRNYHFIQEKN-UHFFFAOYSA-N 0.000 claims abstract description 22
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims abstract description 20
- 229960004316 cisplatin Drugs 0.000 claims abstract description 20
- 208000009304 Acute Kidney Injury Diseases 0.000 claims abstract description 11
- 208000033626 Renal failure acute Diseases 0.000 claims abstract description 11
- 201000011040 acute kidney failure Diseases 0.000 claims abstract description 11
- 229920002125 Sokalan® Polymers 0.000 claims description 26
- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 229940018564 m-phenylenediamine Drugs 0.000 claims description 8
- 229920000642 polymer Polymers 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 6
- 239000004584 polyacrylic acid Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- 229920002873 Polyethylenimine Polymers 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 17
- 241000699670 Mus sp. Species 0.000 abstract description 14
- 239000002086 nanomaterial Substances 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 24
- 239000006143 cell culture medium Substances 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 10
- 239000002609 medium Substances 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- UJHBVMHOBZBWMX-UHFFFAOYSA-N ferrostatin-1 Chemical compound NC1=CC(C(=O)OCC)=CC=C1NC1CCCCC1 UJHBVMHOBZBWMX-UHFFFAOYSA-N 0.000 description 5
- 239000000411 inducer Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 4
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 4
- 238000007865 diluting Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 4
- 229940055619 selenocysteine Drugs 0.000 description 4
- 235000016491 selenocysteine Nutrition 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000010998 test method Methods 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 3
- 108010019160 Pancreatin Proteins 0.000 description 3
- 241000212749 Zesius chrysomallus Species 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 150000002696 manganese Chemical class 0.000 description 3
- 229910052748 manganese Inorganic materials 0.000 description 3
- 239000011572 manganese Substances 0.000 description 3
- 229940055695 pancreatin Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000004697 Polyetherimide Substances 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012984 biological imaging Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001601 polyetherimide Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/44—Elemental carbon, e.g. charcoal, carbon black
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medical Informatics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
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- Urology & Nephrology (AREA)
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- Manufacturing & Machinery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of specific application or application of a nano structure, and particularly relates to application of a selenocarbon dot in preparation of a medicament for inhibiting iron death or a medicament for treating acute nephritis. When the selenocarbon is applied to preparation of the iron death inhibiting medicine, the invention can stably inhibit cell iron death induced by RSL3 and Erastin for a long time; when applied to preparing the medicine for treating acute nephritis, the cisplatin-induced acute kidney injury relieving medicine has good effect of relieving the acute kidney injury of mice induced by cisplatin.
Description
Technical Field
The invention belongs to the technical field of specific application or application of nano structures, and particularly relates to application of selenocarbon dots in preparation of iron death inhibiting medicines or medicines for treating acute nephritis.
Background
Iron death is a regulated cell death mechanism that has been shown to be closely related to many diseases such as kidney disease, heart disease and liver disease, but currently the widely used inhibitors designed for the iron death pathway, such as Ferrostatin-1, are expensive and have insignificant effects in inhibiting iron death induced by certain drugs; the same problems exist with the iron chelators DFO and DFP, while the dose is more difficult to control. With the development of the nano material in the biomedical field, the designed different nano materials have good application effects in the aspects of targeted drug delivery, biological imaging and the like, and the effect of inhibiting iron death is also proved.
For example, in the prior art, a manganese-based nano enzyme preparation is disclosed, a divalent manganese salt or a solution containing the divalent manganese salt is mixed with a dispersion liquid and then dripped into a precipitant solution, hydrothermal reaction is carried out for 20-36 hours at the temperature of 100-150 ℃ under oxygen-containing conditions, fibrous or spherical manganese-based nano enzyme is obtained after purification, polyacrylic acid, polyetherimide or sodium oleate is adopted for surface modification, and when the modified manganese-based nano enzyme is applied to embryonic fibroblasts of mice and living mice, the manganese-based nano enzyme preparation is found to be used as an iron death inhibitor, so that the death of RSL3 and Erastin induced cellular iron can be obviously inhibited, the long-term stable inhibition effect is achieved, and the inhibition and continuous inhibition effect of the nano enzyme preparation on iron death of mice are still required to be further improved.
Disclosure of Invention
The invention aims to overcome the defect or defect of poor iron death inhibition effect of the existing nano material and provides application of a selenocarbon point in preparation of iron death inhibition drugs.
The invention also aims to provide an application of the selenocarbon dots in preparing medicines for treating acute nephritis.
The above object of the present invention is achieved by the following technical solutions:
the invention provides an application of selenocarbon points in preparing medicaments for inhibiting iron death.
When the selenocarbon is applied to preparation of drugs for inhibiting iron death, the selenocarbon has high-efficiency activity of removing active oxygen in cells, can obviously inhibit the iron death of cells induced by RSL3 and Erastin, and can also supplement trace nutrients necessary for human, animal and microorganism health.
Specifically, the selenocarbon dots can be prepared according to the prior art (CN 115029138A), for example, by the following preparation method:
uniformly mixing selenocyamine hydrochloride solution, m-phenylenediamine solution and polymer solution, reacting for 6-10 hours at 160-200 ℃ under the protection of inert gas, and purifying to obtain selenocarbon points;
wherein the polymer solution is a polyacrylic acid solution and/or a polyethyleneimine solution.
Specifically, the mass ratio of selenocysteine hydrochloride to m-phenylenediamine is (1-2) (0.5-1);
the purification process comprises the following steps: the reacted solution is put into a centrifuge tube, centrifuged for 40-60 min at 10000-12000 rpm, the supernatant is taken, and the dialysis is carried out for 24-36 h by selecting 2500-3500 kda dialysis bag.
Preferably, the average particle diameter of the selenocarbon points is 3-5 nm.
When the average particle size of the selenocarbon points is 3-5 nm, the selenocarbon points have better inhibiting effect on cell iron death induced by RSL3 and/or Erastin.
Preferably, the concentration of the selenocarbon point is 4-6 mg/L.
Preferably, the iron death is RSL3 and/or Erastin induced cellular iron death.
The application of the selenocarbon point in preparing the medicament for treating acute nephritis is also within the protection scope of the invention.
Specifically, the selenocarbon dots can be prepared according to the prior art, for example, by the following preparation method:
uniformly mixing selenocyamine hydrochloride solution, m-phenylenediamine solution and polymer solution, reacting for 6-10 hours at 160-200 ℃ under the protection of inert gas, and purifying to obtain selenocarbon points;
wherein the polymer solution is a polyacrylic acid solution and/or a polyethyleneimine solution.
Wherein, the CAS number of the selenocysteine hydrochloride is 3542-13-0, and the CAS number of the m-phenylenediamine is 108-45-2.
Specifically, the mass ratio of selenocysteine hydrochloride to m-phenylenediamine is (1-2) (0.5-1);
the purification process comprises the following steps: the reacted solution is put into a centrifuge tube, centrifuged for 40-60 min at 10000-12000 rpm, the supernatant is taken, and the dialysis is carried out for 24-36 h by selecting 2500-3500 kda dialysis bag.
Preferably, the average particle diameter of the selenocarbon points is 3-5 nm.
Preferably, the selenocarbon point is used in an amount of 0.5-1.0 mg/kg.
Preferably, the acute nephritis is cisplatin-induced acute kidney injury, and specifically may be cisplatin-induced acute kidney injury of mice.
The invention has the following beneficial effects:
when the selenocarbon point is applied to the preparation of the iron death inhibiting medicine, the selenocarbon point is found to be capable of stably and obviously inhibiting the cell iron death induced by RSL3 and Erastin for a long time; meanwhile, when the selenocarbon is applied to preparing a medicament for treating acute nephritis, the result of HE staining of kidney pathological sections and measuring the content of BUN and CRE in mouse serum can show that the selenocarbon has excellent relieving effect on cisplatin-induced acute kidney injury of mice.
Drawings
FIG. 1 shows that various concentrations of PAA@Se-CDs inhibit RSL3 induced cellular iron death.
FIG. 2 shows that PAA@Se-CDs have remarkable inhibiting effect on RSL3 and Erastin induced cell iron death.
FIG. 3 shows that PAA@Se-CDs have a sustained and stable inhibition effect on RSL3 and Erastin-induced cell iron death.
FIG. 4 is a graph of the HE staining of paraffin sections of PAA@Se-CDs on cisplatin-induced acute kidney injury in mice.
FIG. 5 shows the content of BUN and CRE in serum of cisplatin-induced acute kidney injury in mice.
Detailed Description
The invention is further illustrated in the following drawings and specific examples, which are not intended to limit the invention in any way. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
Reagents and materials used in the following examples are commercially available unless otherwise specified.
Example 1
Preparation of selenocarbon dots (PAA@Se-CDs)
Firstly, 100mg of selenocysteine hydrochloride and 50mg of m-phenylenediamine are dissolved in 10mL of ultrapure water, and the solution A is obtained by uniformly mixing; then 1.8g of polyacrylic acid (Mw=1800) is dissolved in 3mL of ultrapure water and evenly mixed to obtain solution B; and then the solution A and the solution B are mixed and placed in a reaction device, under the protection of nitrogen, the mixture is heated and stirred at 180 ℃ for 8 hours to fully react, the reacted solution is respectively placed in a centrifuge tube with the volume of 1.5mL, the centrifuge tube is centrifuged at 12000rpm for 1 hour, the supernatant is taken, a 3500kda dialysis bag is selected for dialysis for 36 hours, and water is replaced every 12 hours to obtain the selenocarbon point nano solution (namely the selenocarbon point).
The average particle diameter of the selenocarbon points prepared by the method is 3.8+/-0.2 nm.
Example 2
The selenocarbon point (PAA@Se-CDs) inhibits RSL3 to induce cell iron death, and the specific test method is as follows:
s1: taking HK-2 cells in logarithmic growth phase, after pancreatin digestion, 2.5X10 per well 5 (500. Mu.L per well) was inoculated into a 24-well plate and cultured for 24 hours;
s2: the medium was discarded and replaced with a different drug-containing medium as follows;
RSL3 group: RSL3 (iron death inducer) was diluted to 1 μm with cell culture medium;
ferrosistatin-1 group: ferrosistatin-1 (commercial iron death) was performed on cell culture mediaInhibitors) to 10 μm;
rsl3+paa@se-CDs group: the selenocarbon spot in example 1 was diluted with cell culture medium to 2mg/L, 4mg/L and 6mg/L solutions, respectively, and 1. Mu.M RSL3 was added;
s3: after 8h of treatment, the drug-containing medium was discarded, 100 μl of PI dye (diluted with PBS) was added to each well at a final concentration of 4 μΜ, and the results were observed under a fluorescence microscope (PI dye stained dead cells, red spots represent dead cells);
wherein, the cell culture medium is DMEM and contains 1% FBS and 1% diabody.
As shown in the figure 1, the detection result is shown in the figure 1, RSL3 can induce a large amount of death of HK-2 cells, and selenocarbon (PAA@Se-CDs) can effectively inhibit RSL3 from inducing cell iron death, and the inhibition effect is related to the concentration of selenocarbon, when the concentration of selenocarbon is 4mg/L and 6mg/L, the selenocarbon has better inhibition effect and is basically equivalent to that of commercial iron death inhibitor Ferrosin-1, and the selenocarbon has excellent inhibition effect on cell iron death induced by RSL 3.
Example 3
Selenocarbon spot (PAA@Se-CDs) inhibition RSL3 and Erastin induced cell iron death test, the specific test method is as follows:
s1: taking HK-2 cells in logarithmic growth phase, after pancreatin digestion, 2.5X10 per well 5 (500. Mu.L per well) was inoculated into a 24-well plate and cultured for 24 hours;
s2: the medium was discarded and replaced with the following medicated medium;
RSL3 group: RSL3 (iron death inducer) was diluted to 1 μm with cell culture medium;
erastin group: diluting Erastin (iron death inducer) to 10. Mu.M with cell culture medium;
ferrosistatin-1 group: ferrosistatin-1 (commercial iron death inhibitor) was diluted to 10. Mu.M with cell culture medium;
Erastin+PAA@Se-CDs group: diluting selenocarbon spot (PAA@Se-CDs) with cell culture medium to 6mg/L solution, and adding 10 μm Erastin
rsl3+paa@se-CDs group: the selenocarbon spot (PAA@Se-CDs) of example 1 was diluted to a solution of 6mg/L with cell culture medium and 1. Mu.M RSL3 was added;
Erastin+Ferrostatin-1 group: the cell culture medium contains 10 mu M of Erastin and 10 mu M of Ferrostatin-1;
rsl3+ferrostatin-1 group: the cell culture medium contains 1 mu M RSL3 and 10 mu M Ferrostatin-1;
s3: after 4h of treatment, the drug-containing medium was discarded, 100 μl of PI dye (diluted with PBS) was added to each well at a final concentration of 4 μΜ, and the results were observed under a fluorescence microscope (PI dye stained dead cells, red spots represent dead cells);
wherein, the cell culture medium is DMEM and contains 1% FBS and 1% diabody.
As shown in FIG. 2, the results of the detection show that the PAA@Se-CDs have remarkable inhibition effect on the cell iron death induced by RSL3 and Erastin, and compared with a positive control group (Ferrostatin-1 treatment), the inhibition effect on the cell iron death is equivalent.
Example 4
Continuous inhibition test of selenocarbon point (PAA@Se-CDs) on cell iron death is carried out by the following specific test method:
s1: taking HK-2 cells in logarithmic growth phase, after pancreatin digestion, 2.5X10 per well 5 (500. Mu.L per well) was inoculated into a 24-well plate and cultured for 24 hours;
s2: the medium was discarded and replaced with the following medicated medium;
RSL3 group: RSL3 (iron death inducer) was diluted to 1 μm with cell culture medium;
erastin group: diluting Erastin (iron death inducer) to 10. Mu.M with cell culture medium;
rsl3+paa@se-CDs group: the selenocarbon spot (PAA@Se-CDs) of example 1 was diluted to a solution of 6mg/L with cell culture medium and 1. Mu.M RSL3 was added;
Erastin+PAA@Se-CDs group: diluting selenocarbon dots (PAA@Se-CDs) into a solution of 6mg/L by using a cell culture medium, and adding 10 mu M of Erastin;
s3: after treating HK-2 cells in the above culture medium for 12h, 24h, 36h, 48h, 72h and 96h, respectively, the drug-containing culture medium was discarded, 100. Mu.L of PI dye solution (diluted with PBS) was added to each well at a final concentration of 4. Mu.M, and the results were observed under a fluorescence microscope (PI dye solution was used to dye dead cells, and red spots represent dead cells);
wherein, the cell culture medium is DMEM and contains 1% FBS and 1% diabody.
As shown in FIG. 3, it can be seen from FIG. 3 that PAA@Se-CDs have a sustained and stable long-term inhibition effect on RSL3 or Erastin-induced cell iron death, and the inhibition effect can last for at least 96 hours.
Example 5
Treatment test of Cisplatin (Cisplatin) induced acute kidney injury by selenocarbon spot (PAA@Se-CDs) is carried out by the following specific test method:
(1) 24C 57BL/6J male mice of 8-10 weeks of age were selected and randomly divided into the following 4 groups (6 per group):
control group: injecting physiological saline into the abdominal cavity;
group paa@se-CDs: tail vein injection PAA@Se-CDs 0.5mg/kg;
cisplatin group: injecting Cisplatin 20mg/kg into the abdominal cavity;
Cisplatin+PAA@Se-CDs group: cisplatin 20mg/kg and tail vein PAA@Se-CDs 0.5mg/kg (simultaneous).
(2) Acute kidney injury is induced by Cisplatin, and male C57BL/6J mice (8-10 weeks old, 18-20 g) are fasted 15 hours before the start of the experiment, but can drink water freely. After the injection treatment, all mice were free to drink and eat.
(3) Mice were sacrificed 72h after all injections were completed on day 1 to take kidney tissue, samples were fixed with 4% paraformaldehyde, paraffin-embedded sections were then HE stained for histological analysis of kidney function, and the detection results are shown in fig. 4. Serum from all the above-mentioned mice in the experimental group was used for the renal function test analysis, and the test results are shown in FIG. 5.
As can be seen from FIG. 4, the accumulation of necrotic tissue in the lumen of the Cisplatin+PAA@Se-CDs treated group was significantly reduced as compared to the Cisplatin treated group; meanwhile, according to fig. 5, compared with the Cisplatin treatment group, the content of BUN and CRE in the serum of mice in the Cisplatin+PAA@Se-CDs treatment group is obviously reduced, which fully shows that the selenocarbon point has good effect of relieving acute kidney injury of mice induced by Cisplatin.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. An application of selenocarbon in preparing medicine for inhibiting iron death is provided.
2. The use according to claim 1, wherein the selenocarbon dots are produced by the following production method:
uniformly mixing selenocyamine hydrochloride solution, m-phenylenediamine solution and polymer solution, reacting for 6-10 hours at 160-200 ℃ under the protection of inert gas, and purifying to obtain selenocarbon points;
wherein the polymer solution is a polyacrylic acid solution and/or a polyethyleneimine solution.
3. The use according to claim 2, characterized in that the average particle size of the selenocarbon dots is 3-5 nm.
4. The use according to claim 1, characterized in that the concentration of selenocarbon sites is 4-6 mg/L.
5. The use according to any one of claims 1 to 4, wherein the iron death is RSL3 and/or Erastin induced cellular iron death.
6. An application of selenocarbon in preparing medicine for treating acute nephritis is provided.
7. The use according to claim 6, wherein the selenocarbon dots are produced by the following production method:
uniformly mixing selenocyamine hydrochloride solution, m-phenylenediamine solution and polymer solution, reacting for 6-10 hours at 160-200 ℃ under the protection of inert gas, and purifying to obtain selenocarbon points;
wherein the polymer solution is a polyacrylic acid solution and/or a polyethyleneimine solution.
8. The use according to claim 7, wherein the average particle size of the selenocarbon dots is 3-5 nm.
9. The use according to claim 6, wherein the selenocarbon dots are used in an amount of 0.5-1.0 mg/kg.
10. The use according to any one of claims 6 to 9, wherein the acute nephritis is cisplatin-induced acute kidney injury.
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