CN116019929A - Nanoparticle modified based on polyphenol compounds and preparation and application thereof - Google Patents
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Abstract
The invention relates to a nanoparticle modified based on a polyphenol compound, and preparation and application thereof. The nano particles are made of Cu 2‑x Se (x is more than or equal to 0 and less than or equal to 1) nano particles are taken as a main body, polyphenol compounds are used for modifying the surfaces of the nano particles, and the nano particles with the antioxidation protection effect are obtained by reasonably using different surface modifiers. The preparation method can obtain the nano particles with adjustable size, good water dispersibility, good biocompatibility and strong antioxidation. The invention also discloses application of the nano-particles after different modifications as novel antioxidants, which can effectively remove Reactive Oxygen Species (ROS), protect neuronal cell injury and improve ischemia reperfusion injury.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a nanoparticle modified based on a polyphenol compound, and preparation and application thereof.
Background
Neurodegenerative diseases such as Alzheimer's Disease (AD), parkinson's Disease (PD), huntington's Disease (HD), amyotrophic Lateral Sclerosis (ALS), and the like have severely compromised the health of the elderly. Among them, PD has become the second most neurodegenerative disease in the world. Although there are various therapeutic approaches including drug therapy, surgical therapy, etc., the complicated and diverse pathogenesis causes PD to be difficult to fundamentally cure. With the aggravation of population aging, many factors such as gene mutation, protein imbalance and the like can accelerate the occurrence and development of PD, and the development of safe and reliable neuroprotective medicaments is particularly important. Drugs currently widely used for neuroprotection are calcium channel blockers, glutamate receptor antagonists, radical scavengers, cell membrane stabilizers, etc., but these small molecule drugs are generally limited to the following problems: (1) poor water solubility, greatly reducing the bioavailability; (2) is easy to be degraded and metabolized, and the internal circulation time is short; (3) The protection effect is single, and the nerve protection effect with multiple surfaces and multiple angles cannot be realized.
Compared with small molecule neuroprotectors with definite structures and fixed properties, the nanoparticle has the advantages of larger specific surface area, modifiable property, diagnosis and treatment integration and the like, and has been widely applied to preclinical researches of various serious diseases. The physical and chemical properties of the nano material can be effectively improved by carefully designing and regulating the size, structure and composition of the nano material. In addition, the surface functionalization of the nanoparticles by utilizing various surface modifications is an extremely important strategy, so that not only the neuroprotection effect of the nanoparticles can be improved, but also the dispersibility, biocompatibility, targeting and the like of the nanoparticles can be improved. Therefore, the surface modification of the nano particles is an important strategy for constructing nano drugs with good water solubility, high safety and multiple neuroprotection.
To construct such neuroprotective agents, patent application number CN202210835211 discloses a hydrogel material synthesized from N-acryloylglycinamide, methacrylic acid acylated gelatin, nanoclay, tannic acid and small extracellular vesicles for spinal cord injury protection and repair. Patent application number CN202210109925 discloses that an endogenous carrier mouse hippocampal cell exosome is utilized to wrap small molecular drug adenosine, and a developed and designed nano drug-carrying transport system shows a protective effect on the behaviours of mice cognitive impairment caused by cerebral ischemia. Patent application number CN202111585161 discloses a sargassum fusiforme polysaccharide nano-selenium which can show a certain neuroprotection effect in a rat model of parkinsonism induced by 6-hydroxydopamine and application thereof, and the nano-selenium is prepared by taking sargassum fusiforme polysaccharide as a template. Patent application number CN202110355826 discloses a preparation method and application of self-assembled nanoparticles of diosgenin derivatives and DHA, and the prepared nanoparticles can be used for protecting inflammatory response of microglia cells caused by LPS. Patent application number CN202210411440 discloses phenolic compounds in hawthorn fruits, a preparation method and application thereof, and discloses that phenolic compounds prepared from hawthorn fruits by a series of chemical methods can play a role in neuroprotection of Parkinson. None of the above patents relates to the modification of nanoparticles with antioxidant polyphenol small molecules to construct nanoparticles with protective effect on neuronal cells and improving kidney damage.
Disclosure of Invention
In order to solve the technical problems, the invention provides a nanoparticle modified based on a polyphenol compound, and preparation and application thereof. The invention effectively improves the antioxidation capability and the bioavailability through the strong coordination action between the copper ions on the surfaces of the nano particles and the polyphenol and flavonoid compounds, and simultaneously provides important microelements copper and selenium for maintaining health. The nano particles have the advantages of low cost of raw materials for preparation, simple construction method, strong antioxidation and neuroprotection effects and high biological safety, and the problems of single function, complex preparation, difficulty in realizing diagnosis and treatment integration and the like are greatly solved.
The invention is realized by the following technical scheme:
it is a first object of the present invention to provide a polyphenol based modified nanoparticle comprising Cu 2-x Se nano particles and surface modifications thereof, wherein the surface modifications are polyphenol compounds; wherein x is more than or equal to 0 and less than or equal to 1; the surface modifier is chelated with Cu by chelation 2-x Se nanoparticles are linked.
In one embodiment of the present invention, the Cu 2-x The particle size of Se nano particles is 1nm-100nm. Further, nanoparticles having a size of less than 20nm are preferred, since smaller nanoparticle sizes provide more surface copper ion characteristics.
In one embodiment of the present invention, the polyphenol compound is selected from flavonoid compounds selected from one or more of Curcumin (Curcumin), biloba extract (Bilobetin), icariin (Icariin), kaempferol (Kaempferol), hesperetin (Hesperetin), catechin (Catechin), and anthocyanin (Anthocyanidin).
In one embodiment of the present invention, the Cu 2-x The mass ratio of the Se nano particles to the surface modification is 1:1-1:50.
In one embodiment of the present invention, the Cu 2-x Se nanoparticles are modified with stabilizers comprising water-soluble sulfhydryl compounds and/or biocompatible molecules.
In one embodiment of the invention, the water-soluble mercapto compound comprises a mono-or poly-mercapto small molecule organic compound comprising one or more of mercaptoethanol, mercaptopropanol, mercaptoacetic acid, mercaptopropionic acid, mercaptosuccinic acid, 2, 3-dimercaptosuccinic acid, mercaptoethylamine; the water-soluble mercapto compound also comprises a polymer macromolecule modified by single mercapto or multiple mercapto, and the polymer macromolecule comprises one or more of polyacrylic acid, polymethacrylic acid and polyvinyl alcohol.
In one embodiment of the invention, the biocompatible molecule comprises a natural polymer and an artificial polymer, wherein the natural polymer comprises one or more of dextran and derivatives thereof, chitosan and derivatives thereof, bovine serum albumin and human serum albumin, the artificial polymer comprises one or more of hydroxyl, carboxyl, amino, sulfhydryl, aldehyde group, ester group polyethylene glycol, homoterminal bifunctional telechelic polyethylene glycol, heteroterminal bifunctional telechelic polyethylene glycol, polyethylene glycol-polyacrylic acid copolymer, polyethylene glycol-polymethacrylic acid copolymer, polyethylene glycol-polyvinylamine copolymer, polyethylene glycol-polylactic acid copolymer, polyvinylpyrrolidone, polyethyleneimine, polyacrylic acid and polyvinyl alcohol, and the molecular weight of the polyethylene glycol is 200-20000.
A second object of the present invention is to provide a method for preparing nanoparticles, which utilizes a "one-pot" method for preparing Cu of different sizes 2-x Se nanoparticles with Cu 2-x The method for constructing the nano-particles with the antioxidation effect comprises the following steps: dripping the polyphenol compound solution into Cu at a certain speed 2-x Stirring in Se nanometer particle solution to accelerate chelation, and finally obtaining Cu modified by polyphenol compound 2-x Se nanoparticles.
In one embodiment of the invention, the drop rate is 1-5 drops per second. The method comprises the following steps: 1 drop/s, 2 drops/s, 3 drops/s, 4 drops/s, 5 drops/s, etc., or any value in between these values.
In one embodiment of the invention, the method further comprises the steps of dialyzing, ultrafiltering and purifying the solution obtained after stirring to remove superfluous polyphenol and flavonoid compounds, and finally obtaining the nano-particles with the antioxidation effect.
In one embodiment of the invention, the stirring conditions are: the stirring temperature is 0-30 ℃, and the stirring time is 10min-12h.
In one embodiment of the present invention, the solvent of the polyphenol and flavonoid compound solution is one or more of ethanol, acetone, dimethyl sulfoxide (DMSO) and Dimethylformamide (DMF). Further, dimethyl sulfoxide (DMSO) is preferable.
In one embodiment of the invention, the concentration of the polyphenol compound solution is 1mg/mL-10mg/mL.
In one embodiment of the present invention, the Cu 2-x The solvent of the Se nanoparticle solution is water and/or DMSO.
In one embodiment of the present invention, the Cu 2-x The concentration of Se nanoparticle solution is 0.1mg/mL-1mg/mL.
In one embodiment of the present invention, the polyphenol compound and the Cu 2-x The molar ratio of Se nano particles is 1:1-1:10.
Further, the preparation method comprises the following steps: cu is added with 2-x Se nano particles are dispersed in aqueous solution, the concentration of copper in the aqueous solution is kept to be 0.1mg/mL-1mg/mL, then organic solvents (such as DMSO, DMF and the like) with the same volume are added, polyphenol and flavonoid compound solutions are added, stirring is carried out at a set temperature, after stirring is carried out for a certain time, the nano particles with different surface modifications can be obtained through the steps of dialysis, centrifugation, ultrafiltration and the like.
A third object of the present invention is to provide the use of the above described nanoparticles in antioxidants.
A fourth object of the present invention is to provide the use of the resulting nanoparticle in the preparation of neuroprotective formulations.
A fifth object of the present invention is to provide the use of the resulting nanoparticle, antioxidant, neuroprotective formulation in neurodegenerative disease drugs, ischemia reperfusion drugs.
In one embodiment of the invention, the neurodegenerative disease is Alzheimer's Disease (AD), parkinson's Disease (PD), huntington's Disease (HD), and Amyotrophic Lateral Sclerosis (ALS).
Compared with the prior art, the technical scheme of the invention has the following advantages:
the nano particle Cu with antioxidation effect of the invention 2-x The Se nano particles and the surface modifier thereof are formed, and the construction method is simple. Cu (Cu) 2-x The surface of Se nano particles is greatly chelated with polyphenol and flavonoid compounds, so that the surface reduction potential is effectively reduced, the oxidation resistance of the surface modification is improved, the water solubility of the Se nano particles is improved, and the bioavailability of the Se nano particles is improved.
The polyphenols and flavonoids of the present invention, except for curcumin, ginkgetin and icariin as described in the examples, are all of the general classes of polyphenols, the more reducing the phenolic hydroxyl groups on the polyphenols, the more sites the substances can be oxidized, and therefore the more reducing. Meanwhile, the oxidation-reduction potential of the metal copper ions after chelation with phenolic hydroxyl groups is lower, so that the reducibility of the pure polyphenol is greatly enhanced.
Compared with large-size nano particles, the size of the nano particles with the oxidation resistance protection effect is adjustable, and the preferable ultra-small nano particles have larger specific surface area, so that more ligands can be modified, and the nano particles are easier to penetrate through a blood brain barrier, thereby providing basic feasibility and safety for in-vivo experiments.
The nano particles have excellent oxidation resistance, can well reach strong oxidation resistance under low concentration, can play a role in protection, and can reduce toxic and side effects caused by large dosage.
The nano-particles of the invention have longer blood circulation time and MPP in vitro + In the induced parkinsonism model, the method has better protection effect, can effectively reduce mitochondrial ROS, protect mitochondria, protect oxidation-reduction balance in cells and reduce neuronal apoptosis, and has higher potential application value in the treatment of parkinsonism in vivo.
The nano particles of the invention show better protection effect in a damage model of mouse kidney ischemia reperfusion, can effectively remove ROS, and has higher potential application value.
The foregoing description is only an overview of the present invention, and is intended to provide a better understanding of the present invention, as it is embodied in the following description, with reference to the preferred embodiments of the present invention and the accompanying drawings.
Drawings
In order that the invention may be more readily understood, a more particular description of the invention will be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings, in which
FIG. 1 is a transmission electron micrograph of CSP nanoparticles in example 1 of the invention.
FIG. 2 is a transmission electron micrograph of BSA-CS nanoparticles in example 1 of the present invention.
FIG. 3 is a transmission electron micrograph of PVP-CS nanoparticles in example 1 of the present invention.
Fig. 4 is the ultraviolet-visible absorption spectra of CSC and CSP in example 2 of the present invention.
FIG. 5 is the UV-visible absorption spectra of CSB and CSP in example 3 of the invention.
Fig. 6 is the ultraviolet-visible absorption spectra of CSI and CSP in example 4 of the present invention.
FIG. 7 is the color of the aqueous solution of CSP, CSC, CSB, CSI in examples 1-4 of the present invention.
FIG. 8 shows the hydrated particle size of CSP, CSC, CSB, CSI in examples 1-4 of the present invention.
Figure 9 is an ultraviolet-visible absorption spectrum of BSA-CSC nanoparticles in example 5 of the present invention.
Figure 10 is an ultraviolet-visible absorption spectrum of PVP-CSC nanoparticles in example 5 of the invention.
Figure 11 is the total antioxidant capacity of CSC nanoparticles at different concentrations in example 6 of the present invention.
Figure 12 is the total oxidation resistance of different nanoparticles at the same copper concentration in example 6 of the present invention.
FIG. 13 is the effect of CSC nanoparticles on SH-SY5Y cell viability in example 7 of the present invention.
Figure 14 is the effect of CSC nanoparticles on ROS production by cell mitochondria in example 8 of the present invention.
Figure 15 is the effect of CSC nanoparticles on neuronal cell mitochondria in example 9 of the present invention.
Figure 16 is the effect of CSC nanoparticles on the redox environment of neuronal cells in example 10 of the present invention.
FIG. 17 is the effect of CSC nanoparticles on apoptosis protein Cle-Caspase 3 in example 11 of the present invention.
Figure 18 is a graph showing the change in antioxidant properties of CSC nanoparticles versus Curcumin alone (Curcumin) in example 12 of the present invention.
FIG. 19 is the effect of CSB nanoparticles on renal function in ischemia reperfusion mice in example 13 of the present invention.
Detailed Description
The present invention will be further described with reference to the accompanying drawings and specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the invention and practice it.
The invention relates to a preparation method of a material
1 Cu used in the present invention 2-x The preparation method of Se nano particles (prepared according to the method of Chinese patent ZL 201610213490.2) comprises the following specific steps:
(1) Dispersing one of selenium powder, sodium selenite, tellurium powder and sodium tellurite in water, wherein the concentration is 1 mmol/L-100 mmol/L, and protecting by inert gas;
(2) Adding sodium borohydride powder into the dispersion system in the step (1), uniformly mixing the sodium borohydride powder with the concentration of 30-300 mmol/L, and reducing the mixture until the solution is colorless;
(3) Adding a mixed aqueous solution of a biocompatible molecule and a metal cation precursor into a colorless low-valence chalcogenide anion solution, wherein the mass ratio of a water-soluble sulfhydryl compound or a biocompatible polymer to a metal cation substance is 20:1-1:1, and stirring and reacting for 1 min-3 h at room temperature; the biocompatible molecules are bovine serum albumin, polyvinylpyrrolidone and the like;
4) After the reaction is finished, the Cu applied by the invention can be prepared by ultrafiltration and separation of the solution for a plurality of times 2-x Se nanoparticles.
Example 1:
the embodiment of the invention provides a preparation method of CSP, BSA-CS and PVP-CS nano particles, which comprises the following steps:
by means of Cu of different sizes 2-x Se nano particles respectively obtain 1-3nm polyvinylpyrrolidone stabilized Cu 2- x Se nanoparticle (CSP), 10-20nm bovine serum albumin stabilized Cu 2-x Se nanoparticles (BSA-CS) and 70-100nm polyvinylpyrrolidone stabilized Cu 2-x Se nanoparticles (PVP-CS). FIGS. 1, 2 and 3 show transmission electron micrographs of CSP, BSA-CS and PVP-CS nanoparticles in sequence.
Example 2:
the embodiment provides a nanoparticle CSC with neuroprotection modified by curcumin, which comprises the following specific steps:
ultra-small Cu stabilized by PVP in example 1 2-x Mixing Se nanoparticle solution (CSP) with curcumin solution dissolved in DMSO, wherein the molar ratio of the nanoparticles to the curcumin is 1:2, keeping the volume ratio of water to DMSO at 1:1, stirring for 4 hours at room temperature, then placing into a dialysis bag with the molecular weight cutoff of 8k-1.4kDa for dialysis for 24 hours to fully remove impurities, finally centrifuging to remove sediment, and performing ultrafiltration concentration to obtain the CSC nanoparticles. Fig. 4 is the ultraviolet-visible absorption spectra of CSC and CSP.
Example 3:
the embodiment provides a bilobalide modified nanoparticle CSB with neuroprotection, which comprises the following steps:
ultra-small Cu stabilized by PVP in example 1 2-x Mixing Se nanoparticle solution with DMSO dissolved biloba extract, wherein the molar ratio of the nanoparticle to the biloba extract is 1:0.5, keeping the volume ratio of water to DMSO at 61:39, stirring for 8 hours in ice water bath, dialyzing for 24 hours in a dialysis bag with the molecular weight cutoff of 8k-14k Da to fully remove impurities, centrifuging to remove sediment, and ultrafiltering and concentrating to obtain the CSB nanoparticle. Fig. 5 shows the ultraviolet-visible absorption spectra of CSB and CSP.
Example 4:
the embodiment provides icariin modified nanoparticle CSI with a neuroprotective effect, which comprises the following specific steps:
ultra-small Cu stabilizing PVP in example 1 2-x Mixing Se nanoparticle solution with icariin dissolved in DMSO, and stabilizing PVP with ultra-small Cu 2-x The molar ratio of Se nano particles to icariine is 1:1, the volume ratio of water to DMSO is kept at 1:1, stirring is carried out for 4 hours at room temperature, then the mixture is put into a dialysis bag with the molecular weight cutoff of 8k-14kDa for dialysis for 24 hours to fully remove impurities, finally, the mixture is centrifuged to remove sediment, and the mixture is ultrafiltered and concentrated to obtain the CSI nano particles. Fig. 6 is the CSI and CSP uv-vis absorption spectra. Fig. 7 and 8 show the aqueous solution color and the hydrated particle size of CSP, CSC, CSB, CSI, respectively.
Example 5:
this example provides curcumin modified large-size Cu 2-x Se nanoparticles, the specific method is as follows:
2 large-sized Cu synthesized in example 1 2-x Se nanoparticles are mixed with DMSO-dissolved curcumin, cu 2- x The molar ratio of Se nano particles to curcumin is 1:2, the volume ratio of water to DMSO is kept at 1:1, stirring is carried out for 4 hours at room temperature, the DMSO stirring solution with the same volume is added until the solution is clear and transparent, centrifugation is carried out at 20,000rpm for 10 minutes, supernatant is discarded, water is added for re-dissolution, and curcumin modified BSA-CS nano particles (BSA-CSC nano particles) and curcumin modified PVP-CS nano particles (PVP-CSC nano particles) are respectively obtained after repeating for 2 times. Fig. 9, 10 are uv-vis absorption spectra of BSA-CSC nanoparticles and PVP-CSC nanoparticles, respectively.
Example 6:
this example provides an in vitro antioxidant capacity assay for the resulting nanoparticles
The oxidation resistance of CSC nanoparticles at concentrations of 6.25 μm, 12.5 μm, 25 μm, and the oxidation resistance of different modified nanoparticles at the same copper concentration were tested using the total oxidation resistance test kit (ABTS rapid method). Fig. 11 shows the antioxidant capacity of CSC nanoparticles at different concentrations, and as can be seen from fig. 11, the antioxidant capacity of CSC nanoparticles increases with increasing concentration. Fig. 12 shows the total antioxidant capacity of the modified nanoparticles at the same copper concentration, and fig. 12 shows that the antioxidant performance of CSC nanoparticles is the best at the same copper concentration, so CSC nanoparticles were selected for subsequent experimental tests. Graph Pad used one-way analysis of variance with P <0.001 and P <0.0001.
Example 7:
this example provides detection of nanoparticles to increase neuronal cell viability
The neuroprotection of the nanomaterial was detected using an enhanced CCK-8 kit: SH-SY5Y cells were plated in 96-well plates, after which 25. Mu.M CSC nanoparticles were incubated with SH-SY5Y cells for 2h, 3mM MPP was changed + And continuing to incubate for 24 hours, adding 10 mu L of CCK-8 solution into each hole after the time is over, incubate for 1 hour at 37 ℃ in a dark place in an incubator, and detecting the absorbance at 450nm by using an enzyme-labeled instrument, wherein the experimental result is shown in FIG. 13. From the figure, CSC nanoparticles increase SH-SY5Y cell resistance to MPP + Damaged cell viability. Graph Pad adopts single factor analysis of variance, P<0.0001。
Example 8:
this example provides a test for the ability of nanoparticles to scavenge free radicals from cellular mitochondria
Detection of ROS in mitochondria by immunofluorescent staining verifies the antioxidant protection of nanoparticles: SH-SY5Y cells were plated into eight-well confocal dishes, 25. Mu.M CSC nanoparticles were incubated with SH-SY5Y cells for 2h before changing 3mM MPP + The co-incubation was continued for 24h. Then 100 μl of mitochondrial ROS probe working solution was added to each well, incubated in an incubator at 37deg.C in the absence of light for 1h, then PBS was washed 2 times, and finally fluorescence distribution and intensity in the cells were observed using a laser confocal scanning microscope. Figure 14 shows that CSC nanoparticles can effectively reduce MPP + The resulting injury, the removal of overproduced ROS.
Example 9:
this example provides detection of the protective effect of nanoparticles on neuronal cell mitochondria
The protection effect of the nanoparticle on mitochondria in neuron cells was detected by immunofluorescence staining: SH-SY5Y cells were plated into eight-well confocal dishes, 25. Mu.M CSC nanoparticles were preincubated with SH-SY5Y cells for 2h before changing 3mM MPP + The co-incubation was continued for 24h. Then 100. Mu.L of wire pellets were added to each wellThe volume tracer probe working solution is incubated for 30min at 37 ℃ in an incubator in the absence of light, then PBS is used for cleaning for 2 times, and the fluorescence distribution and the intensity in the cells are observed by using a laser confocal scanning microscope, and the experimental result is shown in figure 15. Figure 15 shows that CSC nanoparticles can effectively reduce mitochondrial damage in neuronal cells.
Example 10:
this example provides detection of the effect of nanoparticles on the redox environment within a neuronal cell
Detecting influence of nano particles on oxidation reduction in neuron cells by using a detection kit of reduced Glutathione (GSH) and oxidized glutathione (GSSG), sequentially detecting the content of total 5 glutathione and reduced glutathione according to a kit instruction, wherein the difference value of the total 5 glutathione and the reduced glutathione is the content of oxidized glutathione,
finally, the ratio of GSH/GSSG is obtained. The experimental components are control group (Ctrl) and MPP + Group, csc+mpp +
Group, experimental results are shown in fig. 16. Figure 16 shows CSC nanoparticles can protect the redox environment of neuronal cells. Graph Pad adopts one-factor analysis of variance, P <0.05, P <0.01, ns have no significant difference.
0 example 11:
this example provides for the detection of the effects of nanoparticles on neuronal apoptosis
Activation expression of clear-Caspase 3 by immunofluorescence assay verifies neuroprotective effects of nanoparticles: SH-SY5Y cells were plated onto glass slide in 6 well plates and 25. Mu.M CSC
Nanoparticles were incubated with SH-SY5Y cells for 2h, replacing 3mM MPP + Then the co-incubation is continued for 24 hours, after the 5-cultivation is finished, the steps of fixation, membrane rupture, sealing, incubation of primary antibody, combination of secondary antibody, nuclear dyeing and sealing are carried out,
finally, observing the expression of clear-Caspase 3 in the cells by using a laser confocal scanning microscope, and the experimental result is shown in figure 17. Figure 17 shows that CSC nanoparticles effectively reduce MPP + Apoptosis-causing proteins
Expression of clear-Caspase 3.
Example 12:
0 this example provides a comparative test of nanoparticle and pure curcumin ability to scavenge free radicals in cellular mitochondria
Detection of ROS in mitochondria by immunofluorescent staining verifies the antioxidant protection of nanoparticles: SH-SY5Y cells were plated into eight-well confocal dishes, 25. Mu.M CSC nanoparticles, 25. Mu.M
After incubation of curcumin alone with SH-SY5Y cells for 2h, 3mM MPP was changed + The co-incubation was continued for 245h. Then 100 μl of mitochondrial ROS probe working solution was added to each well, incubated in an incubator at 37deg.C in the absence of light for 1h, then PBS was washed 2 times, and finally fluorescence distribution and intensity in the cells were observed using a laser confocal scanning microscope. Figure 18 shows that CSC nanoparticles can significantly enhance the ability to clear overproduction of mitochondrial ROS compared to curcumin alone.
Example 13:
this example provides the therapeutic effect of CSB nanoparticles on mouse kidney ischemia reperfusion injury (I/R).
By constructing a kidney I/R mouse model, the effect of CSB nanoparticles on kidney function of the kidney I/R mouse model is observed: c57BL/6 mice were randomly divided into Sham group, iri+pbs group, iri+csb group (n=3), preoperatively fasted for 8-12h, 2.5% sodium pentobarbital was given to the mice preoperatively, intraperitoneal injection anesthesia was performed, renal pedicles were exposed at the back incision, renal pedicles were rapidly clamped with a non-invasive vascular clamp, the vascular clamp was loosened after maintaining the renal ischemic state for 30min, blood perfusion was resumed, and the surgical incision was sutured after surgery in layers. The rest of the procedure was the same without pinching the renal pedicles in the sham group. The model is constructed successfully, the conventional feeding and the drug treatment are carried out after the operation: CSB nanoparticle groups were treated with 100 μg/mL (200 μl volume) tail vein dosing at 2h and 24h, respectively, model groups were given the same PBS, the whole procedure recorded the mice weight change, and finally the eyeballs were bled for renal function detection. Fig. 19 shows that CSB nanoparticles can effectively improve renal injury caused by renal ischemia reperfusion in mice.
In conclusion, the invention provides the preparation of the nano-particles with high biocompatibility and oxidation resistance and protection effects, and the nano-particles can inhibit neurotoxicity and improve kidney function injuryIn the aspect of application, the nano particles which can be used for oxidation protection are obtained through stirring and mixing reaction, dialysis, ultrafiltration and centrifugation under simple and convenient conditions, and the preparation method is mild, cheap, rapid and efficient, and the prepared nano particles are uniform in size, good in water solubility and good in biocompatibility. At the same time due to Cu 2-x The Se nano particles have excellent photo-thermal conversion performance, can be used for potential in-vivo photo-acoustic imaging, and realize integration aiming at treatment.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, and it should be noted that it is possible for those skilled in the art to make several improvements and modifications without departing from the technical principle of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention.
Claims (10)
1. A nanoparticle modified based on a polyphenol compound, characterized in that the nanoparticle comprises Cu 2-x Se nano particles and surface modifications thereof, wherein the surface modifications are polyphenol compounds; wherein x is more than or equal to 0 and less than or equal to 1.
2. The nanoparticle of claim 1, wherein the Cu 2-x The particle size of Se nano particles is 1nm-100nm.
3. The nanoparticle according to claim 1, wherein the polyphenolic compound is selected from flavonoids; the flavonoid compound is selected from one or more of curcumin, biloba extract, icariin, kaempferol, hesperidin, catechin and anthocyanin.
4. The nanoparticle of claim 1, wherein the Cu 2-x Se nanoparticles are modified with stabilizers comprising water-soluble sulfhydryl compounds and/or biocompatible molecules.
5. The nanoparticle of claim 1, wherein the Cu 2-x The mass ratio of the Se nano particles to the surface modification is 1:1-1:50.
6. A method of preparing the nanoparticle of any one of claims 1-5, comprising the steps of: adding polyphenol compound solution into Cu 2-x Stirring in Se nanometer particle solution to obtain Cu modified by polyphenols 2-x Se nanoparticles.
7. The method of claim 6, further comprising dialysis, ultrafiltration and purification of the solution after stirring.
8. Use of the polyphenol based modified nanoparticles according to any of claims 1 to 5 in antioxidants.
9. Use of the polyphenol-based modified nanoparticle according to any of claims 1 to 5 for the preparation of a neuroprotective formulation.
10. The polyphenol-modified nanoparticle according to any one of claims 1 to 5, and the polyphenol-modified Cu according to the preparation method according to any one of claims 6 to 7 2-x Use of Se nanoparticles, an antioxidant according to claim 8, a neuroprotective formulation according to claim 9 in medicaments for neurodegenerative diseases, and in medicaments for ischemia reperfusion.
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| CN114763533A (en) * | 2022-05-17 | 2022-07-19 | 深圳市第二人民医院(深圳市转化医学研究院) | Method for growing nano-selenium on surface of exosome in situ and obtained selenized exosome |
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| CN114763533A (en) * | 2022-05-17 | 2022-07-19 | 深圳市第二人民医院(深圳市转化医学研究院) | Method for growing nano-selenium on surface of exosome in situ and obtained selenized exosome |
| CN114763533B (en) * | 2022-05-17 | 2024-02-23 | 深圳市第二人民医院(深圳市转化医学研究院) | Method for in-situ growth of nano-selenium on surface of exosome and obtained selenized exosome |
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