CN103948935A - Nano-particle for inhibiting aggregation of alpha-beta and metal ions induced alpha-beta, as well as preparation and application - Google Patents
Nano-particle for inhibiting aggregation of alpha-beta and metal ions induced alpha-beta, as well as preparation and application Download PDFInfo
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Abstract
The invention belongs to the technical field of nano-medicaments, and discloses a nano-particle for inhibiting aggregation of alpha-beta and metal ion induced alpha-beta, as well as a preparation method and application thereof. The nano-particle is Y-modified nano-ruthenium and/or selenium nano-particle, and Y is at least one of arginine, histidine, glucose, saccharose, vitamin C and gallic acid; the Y-modified nano-particle comprises nano-ruthenium, nano-selenium and composite nano-ruthenium-selenium, can be used for inhibiting spontaneous aggregation of alpha-beta, has the effect of inhibiting aggregation of metal ion induced alpha-beta polypeptide, and can be applied to preparation of anti-alzheimer disease medicaments. According to the nano-particle modified by vitamin C and gallic acid, the vitamin C and the gallic acid are directly used as a reducing agent and a modifying agent, other auxiliary reagents need not to be added in the preparation process, the product system and the operation are simple, the method is simple and easy, and the product can be directly stored and used.
Description
Technical field
The invention belongs to Nano medication technical field, particularly a kind of nanoparticle that suppresses A β and metal ion induction A beta peptide aggregation and its preparation method and application.
Background technology
Alzheimer (AD) is a kind of carrying out property neurodegenerative disease taking memory and cognition dysfunction as principal character, also claims senile dementia.AD is mainly in old group, and more than 60 years old in crowd, the prevalence of AD is about 5～10%, and more than 85 years old in crowd the prevalence of AD sharply increase, up to 40～50%.Along with the aggravation of the aging of population and lack the means of effectively prediction and treatment, AD patient's quantity is increasing always, expects the year two thousand fifty global AD patient's quantity and will reach 1.15 hundred million.AD patient's mean survival time (MST) is only 5.5 years, and this disease has become after heart disease, cancer, apoplexy, causes the fourth-largest cause of disease of old people's death.The effect that the medicine of the treatment AD researching and developing according to AD symptom clinically brings is always both worried and glad, clinical practice acetylcholinesteraseinhibitors inhibitors and N-methyl-D-aspartate (NMDA) are for example entered at present, although the decline that these medicines can appropriateness alleviate AD symptom or slow down cognitive competence, can not stop the pathology process of AD.Therefore, be significant according to the anti-AD medicine of the pathogeny development of new of AD.
The feature that AD patient's brain shows assembles as amyloid beta (A β) appears in the neuron of the dwindling of large brain volume, Hippocampus and neopallium and decrease of synapses, extracellular the neurofibrillary tangles that the senile plaque that forms and endocellular phosphorus acidify Tau albumen form.Wherein, the amyloid plaques that A beta peptide aggregation forms is an effective AD neuro pathology mark.Current amyloid cascade hypothesis is thought in normal human's body, the generation of A β and a balance of removing existence, and in AD patient body, this balance is broken the formation that causes A β deposition.The polypeptide that A β is made up of 36～43 aminoacid is the natural metabolite that APP generates through hydrolysis.APP is soluble through α and the gamma secretase A β producing that degrade, and is the main component of the senile plaque of AD patient's brain A beta peptide aggregation formation through β and the gamma secretase A β 1-40/42 producing that degrades.The content of A β 1-40 accounts for 90% of A β total amount, but A β 1-42 more easily assembles than A β 1-40 and be larger to the toxicity of neurocyte.The senile plaque that A beta peptide aggregation forms plays a crucial role in AD occurs and develops, and therefore, reduces A beta polypeptides and in the deposition of AD patient's brain, treatment AD is had very important significance.
A β can spontaneously be gathered into the aggregation of variform, a kind of is the oligomers being formed by 2～6 polypeptide aggregations, this is also the intermediary forming before fiber, and another kind is the soluble fiber that forms beta sheet lamella structure, and this is the Main Morphology of A beta plaque.A beta peptide aggregation forms fiber and is subject to various factors, as metal ion, pH value, A beta polypeptides concentration and other protein etc.Wherein metal ion is one of key factor of induction A beta peptide aggregation.In AD patient's brain A beta plaque, the concentration of part metals ion significantly increases.Particularly, transition metal zinc, copper, ferrum etc. not only can induce A β formation β-pleated sheet also relevant with the neurotoxicity of A β.Research discovery copper ion can be combined by the His on A β, makes it form histidine bridge, and this copper-A beta composite has very strong neurotoxicity.And on the other hand, the copper ion with oxidation-reduction quality is combined rear catalysis H with A β
2o
2formation.Excessive H
2o
2penetrate cell membrane, if uncatalyzed decomposition is by forming reactive high hydroxyl radical free radical, cause the oxidative damage such as DNA damage, lipid peroxidation.Because A β 1-42 has higher binding affinity to copper ion, thereby A β 1-42 more easily assembles than A β 1-40.
According to above research, reduce the content of metal ion in A beta plaque and 2 main method that metal ion is assembled in conjunction with the A beta polypeptides that is the induction of inhibition metal ion with A beta polypeptides.What suppress by metal-chelator that the A beta polypeptides of metal ion induction assembles is the effective ways for the treatment of AD.The A beta polypeptides that particularly nioform (CQ) and derivant PBT2 thereof can not only suppress the induction of zinc, copper ion is assembled, is reduced the generation of A beta plaque and ROS, and can improve the cognitive competence of AD mice.But most metal-chelator cannot see through blood brain barrier, in addition, metal-chelator does not have selectivity to the chelating of metal ion, thereby some necessary metal ions in chelating health are produced toxic and side effects by this.
Summary of the invention
In order to overcome the shortcoming and deficiency of above-mentioned prior art, primary and foremost purpose of the present invention is to provide the nanoparticle of a kind of A of inhibition β and metal ion induction A beta peptide aggregation.
Another object of the present invention is the preparation method of the nanoparticle that a kind of above-mentioned inhibition A β and metal ion induction A beta peptide aggregation are provided.
Still a further object of the present invention is to provide the nanoparticle of above-mentioned inhibition A β and metal ion induction A beta peptide aggregation in the application of preparing in anti-alzheimer syndrome medicament.
Object of the present invention realizes by following proposal:
A nanoparticle that suppresses A β and metal ion induction A beta peptide aggregation, this nanoparticle is nanometer ruthenium and/or the Se particle that Y modifies, Y is at least one in arginine, histidine, glucose, sucrose, vitamin C and gallic acid.
The preparation method of the nanoparticle of above-mentioned inhibition A β and metal ion induction A beta peptide aggregation, in the time that Y is vitamin C or gallic acid, comprises the following steps:
Na
2seO
3and/or RuCl
3wiring solution-forming A, drips Y solution, and cooling leaving standstill is centrifugal, obtains nanoparticle.
In the time that Y is arginine, histidine, glucose or sucrose, comprise the following steps:
By Y and Na
2seO
3and/or RuCl
3wiring solution-forming B, drips sodium borohydride, and cooling leaving standstill is centrifugal, obtains nanoparticle.
The concentration of described Y solution is 0.025～0.1mol/L.
Na used when described solution A or solution B configuration
2seO
3concentration be 0.1mol/L.
RuCl used when described solution A or solution B configuration
3concentration be 0.025～0.1mol/L.
Preferably, in described solution A or solution B, Na
2seO
3and RuCl
3molar concentration rate be 1.5:1～3:1.
Preferably, in described solution A or solution B, Na
2seO
3and RuCl
3molar concentration rate be 2:1.
The amount of Y used and Na
2seO
3and RuCl
3the mol ratio of total amount is 1:1～6:1.
Preferably, the amount of Y used and Na
2seO
3and RuCl
3the mol ratio of total amount is 4:1.
The concentration of sodium borohydride used is 0.025～0.8m
ol/L, the mol ratio of sodium borohydride used and Y is 1:1～6:1.
Described cooling standing finger is cooled to room temperature and places 12～24h.
Preferably, described solution A is heated to 30～40 DEG C before dropping Y solution.
Preferably, centrifugal rear gained nanoparticle washs with pure water.Above-mentioned configuration solution all adopts pure water configuration.
The application of the nanoparticle of above-mentioned inhibition A β and metal ion induction A beta peptide aggregation in the anti-alzheimer syndrome medicament of preparation.
The present invention prepares nanometer ruthenium and/or the Se particle of different modifying agent, utilizes the metal ion binding site on itself and A beta polypeptides, thereby intervenes the combination of metal ion with A beta polypeptides, suppresses the gathering of metal ion induction A beta polypeptides.Research finds to change protein bound to conformation after Nanosurface, and this will affect protein aggregation process.What existing research and development were found can be divided into inorganic nano-particle (nanometer gold, magnetic nano-particle and quantum dot etc.), high molecule nano material and carbon with the nano material of aβ protein combination is basic nano material (fullerene, CNT, Graphene) etc.These nano materials can suppress the gathering of A beta polypeptides effectively, its inhibitory action is mainly because nanometer has compared with bigger serface and stronger absorbability, after nanometer is combined with polypeptide, may cover and be arranged in protein central authorities hydrophobic active site and also reduced the concentration of the amyloid of solution, thereby the fibrosis that has suppressed A beta polypeptides is assembled simultaneously.Dressing agent, nanometer particle size and the surface charge of nanometer all can affect the combination of nanometer with A beta polypeptides.The nanometer that adopts different modifying agent can modify out different-grain diameter and electric charge, and the performance of the nanoparticle preparing by the agent of research different modifying, determine the impact with the binding ability of A beta polypeptides for nanometer of dressing agent, nanometer particle size and surface charge, the nanoparticle that the present invention utilizes arginine, histidine, glucose, sucrose, vitamin C and gallic acid to modify, the inhibition metal ion with obvious excellence is induced the effect of A beta polypeptides gathering, can be applicable to prepare in anti-alzheimer syndrome medicament.
The present invention, with respect to prior art, has following advantage and beneficial effect:
(1) the Y decorated nanometer particle that prepared by the present invention has comprised nanometer ruthenium, nanometer selenium, composite Nano selenium/ruthenium, this Y decorated nanometer particle can not only suppress the spontaneous gathering of A β, and have and suppress the effect that the metal ion A beta polypeptides of inducing is assembled, can be applicable to prepare anti-alzheimer syndrome medicament.
(2) nanoparticle that the vitamin C that prepared by the present invention and gallic acid are modified is directly taking vitamin C and gallic acid as reducing agent and dressing agent, preparation process is simple without other auxiliary reagent of interpolation, product system, arginine, histidine, glucose, sucrose are as dressing agent, can improve the biocompatibility of nanometer, the stability of the nanometer ruthenium of modifying in addition, is high.Simple to operate, method is simple and easy, and product can directly be preserved and use.
Brief description of the drawings
Fig. 1 is nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium shape appearance figure that arginine is modified.
Fig. 2 is the transmission electron microscope picture that nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium of arginine modification is combined with A β 40 polypeptide.
Fig. 3 is the inhibitory action of arginine nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium the modified A β 40 polypeptide aggregation somatic nerves toxicity to zinc ion induction.
Fig. 4 is that the atom that nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that arginine is modified suppress zinc ion induction A β 40 polypeptide aggregations is tried hard to.
Fig. 5 is that nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium that arginine is modified reduces the result figure that assembles the caused neuronal apoptosis of A β 40 polypeptide.
Detailed description of the invention
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited to this.
As long as raw materials used purity reaches chemical pure above in the following example, source all can be buied from market.
Embodiment 1: the preparation of nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that arginine is modified
(1) take 0.1729g sodium selenite, be settled to 10mL with distilled water and be mixed with 0.1mol/L storage liquid; Take 0.0435g arginine simultaneously, be settled to 10mL with distilled water and be mixed with 0.025mol/L storage liquid; Take 0.0259g ruthenium trichloride, be settled to 5mL with distilled water and be mixed with 0.025mol/L storage liquid.
(2) getting 0.2mL sodium selenite storing solution mixes with different proportion arginine, under the condition of 400rpm/min, drip gradually the sodium borohydride of different proportion, color transition is to stop after brick-red stirring, illustrate and restore nanometer selenium, the mol ratio of sodium selenite and arginine or sodium borohydride is respectively 1:1,1:2,1:3,1:4,1:5,1:6.Wherein, the sample that in the nanometer selenium that arginine is modified, sodium selenite and arginic mol ratio are 1:4 is the most stable, and the mol ratio of sodium selenite and sodium borohydride is 1:4.Above-mentioned solution is placed to 12h at 4 DEG C, and centrifugalize, abandons supernatant, and washing, is settled to 10mL, obtains the nanometer selenium that 2mM arginine is modified.Observe by TEANAI-10 type transmission electron microscope (TEM), as shown in Figure 1A.Obtain the dispersion of nanoparticle, its particle diameter is in 110nm left and right.At room temperature stable existence of this nanoparticle, easily preserves.
(3) step of the nanometer ruthenium that arginine is modified is similar to (2), getting 0.4mL ruthenium trichloride storing solution mixes with different proportion arginine, under the condition of 400rpm/min, drip gradually the sodium borohydride of different proportion, color transition is after cinerous, to stop stirring, and final ruthenium trichloride and arginic mol ratio are respectively 1:1,1:2,1:3,1:4,1:5,1:6.The most stable when in the nanometer ruthenium that arginine is modified, ruthenium trichloride and arginic mol ratio are 1:4, the mol ratio of sodium selenite and sodium borohydride is similarly 1:4.This solution is placed 12h at 4 DEG C, and supernatant is abandoned in centrifugalize, and washing, is settled to 10mL, obtains the nanometer ruthenium that 2mM arginine is modified.Observe by TEANAI-10 type transmission electron microscope (TEM), as shown in Figure 1B.Obtain the dispersion of nanoparticle, its particle diameter is in 30nm left and right.At room temperature stable existence of this nanoparticle.
(4) get 0.2mL sodium selenite and 0.4mL ruthenium trichloride storing solution and arginine (arginine and sodium selenite and ruthenium trichloride total amount and mol ratio are 4:1) Hybrid Heating to 40 DEG C, the reducing agent optimal proportion (sodium borohydride and sodium selenite and ruthenium trichloride total amount and mol ratio are 4:1) optimizing by step (2) and (3) under the condition of 400rpm/min subsequently drips and enters sodium borohydride storing solution.The mol ratio that optimizes selenium and ruthenium in composite Nano selenium/ruthenium that arginine modifies is 2:1.This solution is placed 12h at 4 DEG C, and supernatant is abandoned in centrifugalize, and washing, is settled to 10mL, obtains composite Nano selenium/ruthenium that 2mM arginine is modified.Observe by TEANAI-10 type transmission electron microscope (TEM), as shown in Figure 1 C.Obtain the dispersion of nanoparticle, its particle diameter is in 90nm left and right.At room temperature stable existence of this nanoparticle, easily preserves.
The preparation process of nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium of histidine, glucose or sucrose modified is the same, except reagent is changed to mentioned reagent by arginine.
Embodiment 2: the preparation of nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that gallic acid is modified
(1) take 0.1729g sodium selenite, be settled to 10mL with distilled water and be mixed with 0.1mol/L storage liquid; Take 0.0425g gallic acid simultaneously, be settled to 10mL with distilled water and be mixed with 0.025mol/L storage liquid; Take 0.0259g ruthenium trichloride, be settled to 5mL with distilled water and be mixed with 0.025mol/L storage liquid.
(2) get 0.2mL sodium selenite storing solution, under the condition of 400rpm/min, drip gradually the gallic acid of different proportion, color transition is to stop after brick-red stirring, illustrate and restore nanometer selenium, the mol ratio of final sodium selenite and gallic acid is respectively 1:1,1:2,1:3,1:4,1:5,1:6.Wherein, the sample that in the nanometer selenium that gallic acid is modified, the mol ratio of sodium selenite and gallic acid is 1:4 is the most stable.Above-mentioned solution is placed to 12h at 4 DEG C, and centrifugalize, abandons supernatant, and washing, is settled to 10mL, obtains the nanometer selenium that 2mM gallic acid is modified.At room temperature stable existence of this nanoparticle, easily preserves.
(3) step of the nanometer ruthenium that gallic acid is modified is similar to (2), get 0.4mL ruthenium trichloride storing solution, under the condition of 400rpm/min, drip gradually the gallic acid of different proportion, color transition is after cinerous, to stop stirring, and the mol ratio of final ruthenium trichloride and gallic acid is respectively 1:1,1:2,1:3,1:4,1:5,1:6.It is the most stable when in the nanometer ruthenium that gallic acid is modified, the mol ratio of ruthenium trichloride and gallic acid is 1:4.This solution is placed 12h at 4 DEG C, and supernatant is abandoned in centrifugalize, and washing, is settled to 10mL, obtains the nanometer ruthenium that 2mM gallic acid is modified.At room temperature stable existence of this nanoparticle.
(4) get 0.2mL sodium selenite and 0.4mL ruthenium trichloride storing solution Hybrid Heating to 40 DEG C, the reducing agent optimal proportion (gallic acid and both total amounts and mol ratio are 4:1) optimizing by step (2) and (3) under the condition of 400rpm/min subsequently drips and enters gallic acid storing solution.The mol ratio that optimizes selenium and ruthenium in composite Nano selenium/ruthenium that gallic acid modifies is 2:1.This solution is placed 12h at 4 DEG C, and supernatant is abandoned in centrifugalize, and washing, is settled to 10mL, obtains composite Nano selenium/ruthenium that 2mM gallic acid is modified.At room temperature stable existence of this nanoparticle, easily preserves.
The preparation method of nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that vitamin C is modified is the same.
Nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that embodiment 3:Y modifies are combined with A β 1-40 polypeptide
First get 30 μ M A β
40(purchased from Shanghai GL Biochem Ltd. company) hatches and within 3 days, forms fibrous gathering at 37 DEG C, hatches 6h subsequently toward the modification that adds respectively in this sample 60 μ g/mL embodiment 1 and embodiment 2 to prepare and with the nanoparticle of rhodamine B labelling again.The above-mentioned solution of getting 10 μ L drops in the slide of surface through positive charge processing, after sample drying, observes by under laser confocal microscope.Result shows, nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium that arginine, histidine, glucose, sucrose, vitamin C and the gallic acid that the present invention prepares modified respectively all can with A β
40polypeptide combination, the amount that wherein nanometer ruthenium and composite Nano selenium/ruthenium are combined with polypeptide is more than nanometer selenium, illustrates that the binding ability of nanometer ruthenium and composite Nano selenium/ruthenium and polypeptide is greater than nanometer selenium.
Wherein, the TEM scanning result that nanometer selenium (SeNPs), nanometer ruthenium (RuNPs) and the composite Nano selenium/ruthenium (Se/RuNPs) that arginine is modified is combined with A β 1-40 polypeptide as shown in Figure 2.
The A β of nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium that embodiment 4:Y modifies to zinc ion induction
40the inhibitory action of polypeptide aggregation somatic nerves toxicity
In this experiment, PC12 cell is purchased from ATCC company, and condition of culture is the DMEM culture medium of having added 5% horse serum, 10% Ox blood serum, 5%CO
2, under 37 DEG C of conditions.
MTT method of testing
30 μ M A β
40decorated nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that polypeptide prepares with 60 μ M embodiment 1 and embodiment 2 respectively, at PBS, are hatched 3 days under 37 DEG C of conditions; Get the tumor cell in exponential phase, adjusting viable cell concentrations is 2 × 10
4/ mL is added on 96 well culture plates, and every hole 100 μ L cultivate 24h after adherent in incubator, add respectively difference to hatch sample, and application of sample group and matched group are all established 6 multiple holes, put 37 DEG C, 5%CO
2cultivate 72h, then add MTT(5mg/mL) 20 μ L/ holes, the centrifugal supernatant of abandoning after 5h, adds dimethyl sulfoxide (DMSO) 100 μ L/ holes, and OD value is measured in vibration 10min left and right under 570nm wavelength by microplate reader, calculate cell survival rate.
The OD value of the actual OD value/negative control hole of cell survival rate (%)=medicine feeding hole;
Result shows, the cytotoxicity of nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that arginine, histidine, glucose, sucrose, vitamin C and the gallic acid that the present invention prepares modified is respectively all very low, and cell survival rate reaches 91%.
Wherein, arginine modify nanometer selenium (SeNPs), nanometer ruthenium (RuNPs) and composite Nano selenium/ruthenium (Se/RuNPs) the results are shown in Figure 3, the cytotoxicity of nanometer selenium, nanometer ruthenium and composite Nano selenium/ruthenium that in the present invention, arginine is modified is all very low, and composite Nano selenium/ruthenium can suppress the A β of zinc ion induction effectively
40polypeptide aggregation somatic nerves toxicity, than matched group, cell survival rate reaches 91%.
Embodiment 5: nanometer selenium, nanometer ruthenium and the composite Nano selenium/ruthenium that transmission electron microscope observing Y modifies suppresses zinc ion induction A β
40the variation of polypeptide aggregation form
At 50mM PBS, in pH7.4 solution, 30 μ M A β
40polypeptide respectively with 60 μ M Zn (Ac)
2or/and the decorated nanometer particle for preparing of 60 μ g/mL embodiment 1 and embodiment 2 hatches 3 days under 37 DEG C of conditions.Get the above-mentioned solution of hatching of 10 μ L and drop on the mica sheet of newly riving, when waiting sample half-dried, rinse gently mica sheet, at room temperature dried overnight with distilled water.Sample is by Hitachi-7650 transmission electron microscope observation.Hatch after 3 days independent A β
40polypeptide forms the fibrous gathering that obviously can distinguish, and zinc ion can significantly increase A β
40the amount of polypeptide aggregation, and the nanometer selenium that arginine of the present invention, histidine, glucose, sucrose, vitamin C and gallic acid are modified respectively, nanometer ruthenium and composite Nano selenium/ruthenium all obviously show as the A β that suppresses zinc ion induction
40polypeptide aggregation, wherein, composite Nano selenium/ruthenium most pronounced effects of modification, in this group, A β
40polypeptide only forms short fiber.Illustrate that composite Nano selenium/ruthenium that the present invention prepares can be incorporated into A β
40thereby polypeptide also reduces the A β that the combination of zinc ion and polypeptide suppresses zinc ion induction effectively
40polypeptide aggregation.
Wherein, arginine modify nanometer selenium (SeNPs), nanometer ruthenium (RuNPs) and composite Nano selenium/ruthenium (Se/RuNPs) the results are shown in Figure 4.
The nanometer selenium that embodiment 6:Y modifies reduces assembles A β
40the caused neuronal apoptosis of polypeptide
In 12 well culture plates, the slide that a slice high temperature sterilize is crossed is placed in each hole, and the PC12 cell of the trophophase of taking the logarithm is made cell suspending liquid with 0.1% trypsin solution digestion, and adjusting cell concentration is 1 × 10
5individual/mL, is inoculated on slide, places 40min on superclean bench, adds 1mL culture medium, puts in incubator and cultivates.After cell attachment, add the A β of hatching in advance
40the sample (incubation step is with example 4) of polypeptide and zinc ion or decorated nanometer particle of the present invention.After 48h, slide is taken out, fixes with paraformaldehyde, dye by the requirement in TUNEL test kit description, finally with DAPI dyeing 15min just can Nikon Eclipse TE2000-E fluorescence microscope under the cell concentration of observing apoptosis.The nucleus of apoptosis is dyed to green, and normal nucleus is dyed to blueness.Result shows, zinc ion and A β
40the quantity that polypeptide is hatched sample sets apoptotic cell is jointly significantly higher than independent A β
40polypeptide group, and the nanometer selenium that arginine of the present invention, histidine, glucose, sucrose, vitamin C and gallic acid are modified respectively, nanometer ruthenium and nanometer selenium/ruthenium can significantly reduce the A β that zinc ion is induced
40the neurotoxicity of polypeptide, wherein, the apoptotic cell quantity of composite Nano selenium/ruthenium is minimum.
As shown in Figure 5, nanometer selenium part reduces the quantity of apoptotic cell to the observation figure of nanometer selenium (SeNPs), nanometer ruthenium (RuNPs) and composite Nano selenium/ruthenium (Se/RuNPs) that arginine is modified, illustrates that composite Nano selenium/ruthenium suppresses the A β of zinc ion induction
40the ability of polypeptide aggregation is better than nanometer selenium.
Above-described embodiment is preferably embodiment of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and principle, substitutes, combination, simplify; all should be equivalent substitute mode, within being included in protection scope of the present invention.
Claims (10)
1. suppress A β and metal ion and induce a nanoparticle for its gathering, it is characterized in that this nanoparticle is nanometer ruthenium and/or the Se particle that Y modifies, Y is at least one in arginine, histidine, glucose, sucrose, vitamin C and gallic acid.
2. inhibition A β according to claim 1 and metal ion are induced a preparation method for the nanoparticle of its gathering, it is characterized in that:
In the time that Y is vitamin C or gallic acid, comprise the following steps:
Na
2seO
3and/or RuCl
3wiring solution-forming A, drips Y solution, and cooling leaving standstill is centrifugal, obtains nanoparticle;
In the time that Y is arginine, histidine, glucose or sucrose, comprise the following steps:
By Y and Na
2seO
3and/or RuCl
3wiring solution-forming B, drips sodium borohydride, and cooling leaving standstill is centrifugal, obtains nanoparticle.
3. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: the concentration of described Y solution is 0.025～0.1mol/L.
4. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: Na used when described solution A or solution B configuration
2seO
3concentration be 0.1mol/L.
5. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: RuCl used when described solution A or solution B configuration
3concentration be 0.025～0.1mol/L.
6. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: in described solution A or solution B, and Na
2seO
3and RuCl
3molar concentration rate be 1.5:1～3:1.
7. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: the amount of Y used and Na
2seO
3and RuCl
3the mol ratio of total amount is 1:1～6:1.
8. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: in described solution A or solution B, and Na
2seO
3and RuCl
3molar concentration rate be 2:1; The amount of Y used and Na
2seO
3and RuCl
3the mol ratio of total amount is 4:1.
9. inhibition A β according to claim 2 and metal ion are induced the preparation method of the nanoparticle of its gathering, it is characterized in that: the concentration of sodium borohydride used is 0.025～0.8mol/L, and the mol ratio of sodium borohydride used and Y is 1:1～6:1; Described cooling standing finger is cooled to room temperature and places 12～24h.
10. inhibition A β according to claim 1 and metal ion induce the nanoparticle of its gathering in the application of preparing in anti-alzheimer syndrome medicament.
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| CN107213163A (en) * | 2017-04-20 | 2017-09-29 | 国家纳米科学中心 | Application of the lamella carbon ferroso-ferric oxide complex in A beta peptide aggregations are suppressed |
| CN108743609A (en) * | 2018-07-05 | 2018-11-06 | 江西农业大学 | It is a kind of to have both the nano-particle preparation method and application for inhibiting the aggregation of A beta polypeptides and Scavenger of ROS |
| CN110420218A (en) * | 2019-08-22 | 2019-11-08 | 山东第一医科大学(山东省医学科学院) | Application of the chondroitin sulfate nano-selenium in the drug of preparation treatment cognitive function decline related neurological disease |
| CN110664838A (en) * | 2019-11-07 | 2020-01-10 | 中南大学 | Preparation of quercetin-loaded nano-selenium and application of quercetin-loaded nano-selenium in treatment of Alzheimer's disease |
| CN112451514A (en) * | 2020-11-26 | 2021-03-09 | 江西农业大学 | Dihydromyricetin nano-selenium and preparation method and application thereof |
| CN112641956A (en) * | 2021-02-09 | 2021-04-13 | 福州大学 | Preparation and application of peptide-metal-drug self-assembly nanoparticles for resisting Alzheimer's disease |
| CN114744176A (en) * | 2022-04-29 | 2022-07-12 | 东南大学 | Ruthenium-doped amorphous selenium material for anode of water-based zinc ion battery and preparation method thereof |
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| CN101040869A (en) * | 2007-03-02 | 2007-09-26 | 暨南大学 | Nanometer elemental selenium coupled with liquid amino acid and the method for preparing and preserving the same |
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Cited By (8)
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| CN107213163A (en) * | 2017-04-20 | 2017-09-29 | 国家纳米科学中心 | Application of the lamella carbon ferroso-ferric oxide complex in A beta peptide aggregations are suppressed |
| CN108743609A (en) * | 2018-07-05 | 2018-11-06 | 江西农业大学 | It is a kind of to have both the nano-particle preparation method and application for inhibiting the aggregation of A beta polypeptides and Scavenger of ROS |
| CN108743609B (en) * | 2018-07-05 | 2020-11-27 | 江西农业大学 | Preparation method and application of nanoparticles capable of inhibiting Abeta polypeptide aggregation and eliminating active oxygen |
| CN110420218A (en) * | 2019-08-22 | 2019-11-08 | 山东第一医科大学(山东省医学科学院) | Application of the chondroitin sulfate nano-selenium in the drug of preparation treatment cognitive function decline related neurological disease |
| CN110664838A (en) * | 2019-11-07 | 2020-01-10 | 中南大学 | Preparation of quercetin-loaded nano-selenium and application of quercetin-loaded nano-selenium in treatment of Alzheimer's disease |
| CN112451514A (en) * | 2020-11-26 | 2021-03-09 | 江西农业大学 | Dihydromyricetin nano-selenium and preparation method and application thereof |
| CN112641956A (en) * | 2021-02-09 | 2021-04-13 | 福州大学 | Preparation and application of peptide-metal-drug self-assembly nanoparticles for resisting Alzheimer's disease |
| CN114744176A (en) * | 2022-04-29 | 2022-07-12 | 东南大学 | Ruthenium-doped amorphous selenium material for anode of water-based zinc ion battery and preparation method thereof |
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| CN103948935B (en) | 2017-08-11 |
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