CN112386705A - Gold nanoparticle based on hyaluronic acid modification, preparation method thereof and application of gold nanoparticle as nano-drug carrier - Google Patents
Gold nanoparticle based on hyaluronic acid modification, preparation method thereof and application of gold nanoparticle as nano-drug carrier Download PDFInfo
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Abstract
The invention belongs to the field of chemical biology, and particularly relates to a nano-drug carrier based on gold nanoparticles modified by hyaluronic acid, and a preparation method and application thereof. The nano-drug carrier based on the gold nanoparticles modified by hyaluronic acid has the following general formula:
Description
Technical Field
The invention belongs to the technical field of chemical biology, and particularly relates to gold nanoparticles based on hyaluronic acid modification, a preparation method thereof and application of the gold nanoparticles as a nano-drug carrier.
Background
Gold nanoparticles have a large surface area and a spherical shape, and can be used as a carrier for encapsulating many dye molecules, and have been mainly used for signal recording of fluorescence immunoassay to improve detection sensitivity. Gold nanoparticles are a new type of nanomaterial and, recently, scientists' attention has turned to the possibility of gold nanoparticles for medical use. In view of the characteristic that the photoelectric property of the gold nanoparticle is easy to modify, the gold nanoparticle can be used for cell detection, gene regulation drug synthesis, drug transportation, photochemical treatment and the like. Gold nanoparticles can allow specific substances to enter cells, such as multivalent drugs and antisense factors. These substances can control cellular functions, regulate gene expression, and can also detect intracellular analytes.
Hyaluronic Acid (HA) is a natural source macromolecule, and because of its good biocompatibility, biodegradability, low toxicity and low immunogenicity, it HAs been widely used in biomedical applications, especially in cosmetics, arthritis treatment, and drug delivery. Recent studies have shown that the cancer cell surface is over-expressed with CD44 receptor, and hyaluronic acid is an important binding substance which is combined and expressed with the CD44 receptor, so that the hyaluronic acid is researched and explored as a targeting ligand in tumor targeting drug delivery. The HA structure can be modified to generate various hyaluronic acid derivatives, so that the stability of the hyaluronic acid derivatives is maintained, and the biocompatibility of the hyaluronic acid derivatives is enhanced. HA HAs abundant hydroxyl and carboxyl, and can provide a plurality of chemical modification sites, so that hyaluronic acid can be combined with the gold nanoparticles to be used as a targeting molecule, and can be specifically targeted into CD44 high-expression tumor cells.
Polyethylene glycol (PEG) is used as a bonding agent, has the advantages of no toxicity, good water solubility and the like, is approved by the food and drug administration of the United states for eating and various clinical applications, forms good biocompatibility with a plurality of organic matters, can increase certain solubility when being synthesized with a compound with poor water solubility, can inhibit the adsorption of a transaminase system and reduce the clearance of the transaminase system when the compound enters blood after being modified by PEG, thereby prolonging the blood circulation time and influencing the transportation of a drug delivery system. Thus, PEG has been extensively studied in the fields of controlled drug release, wound healing, drug delivery, and the like. And because the commonly synthesized nano gold particles can be well dispersed in the aqueous solution, the duration is not long enough, and the nano gold particles are easy to aggregate together. In order to overcome the defects, the hyaluronic acid and the nanogold materials are combined to be used as a carrier for transferring small molecules of the medicine, so that the dispersion state of the medicine can be improved, a better absorption effect is achieved, toxic and side effects are reduced, and the curative effect of the medicine is enhanced.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides gold nanoparticles based on hyaluronic acid modification, a preparation method thereof and application of the gold nanoparticles as a nano-drug carrier.
In order to achieve the purpose, the invention adopts the following technical scheme:
a gold nanoparticle based on hyaluronic acid modification has a structural formula as follows:
au is mercaptopropionic acid modified gold nanoparticles.
The preparation method of the gold nanoparticles based on hyaluronic acid modification comprises the following steps:
1) preparation of compound 4 or 7:
dissolving Hyaluronic Acid (HA) in PBS, adding Adipic Dihydrazide (ADH), 1, 2-dichloroethane (EDC) and N-hydroxysuccinimide (NHS), reacting for 20-30h under the condition of room temperature and nitrogen protection, and after the reaction is finished, adding polyethylene glycol (PEG) and continuing to react for 20-30h under the nitrogen protection; after the reaction is finished, obtaining a PEG-HA-ADH compound 4 through dialysis and reduced pressure distillation;
or dissolving Hyaluronic Acid (HA) in PBS, adding polyethylene glycol (PEG), 1, 2-dichloroethane (EDC) and N-hydroxysuccinimide (NHS), reacting for 20-30h at room temperature under the protection of nitrogen, and dialyzing and distilling under reduced pressure to obtain a PEG-HA compound 7 after the reaction is finished;
2) preparation of compound 6: tetrachloroauric acid (HAuCl)4) Dissolving in triple distilled water, heating in dark place to boil, boiling for 10-20min, adding sodium citrate solution, stirring at boiling state for 30-50min, cooling to room temperature to obtain gold solution, and centrifuging to obtain gold nanoparticles; uniformly dissolving the gold nanoparticles in triple distilled water, adjusting the pH value to 10-12 by using 0.1M KOH, then adding an ethanol solution of mercaptopropionic acid to react for 2-3h, and centrifuging to obtain a compound 6, namely gold nanoparticles (Au @ MPA) wrapped by mercaptopropionic acid;
3) uniformly dissolving the compound 6 in triple distilled water, adjusting the pH to 6-7 by using ethanesulfonic acid, then adding 1, 2-dichloroethane (EDC) and N-hydroxysuccinimide (NHS), and stirring for reacting for 30-50 min; then adding the compound 4 or 7, stirring for 20-30h at room temperature, and centrifuging to obtain the compound.
In the preparation method of the gold nanoparticles based on hyaluronic acid modification, the mass ratio of the compound 6 to the compound 4 or 7 is 1: 10.
specifically, in the step 1), the cut-off molecular weight of the dialysis bag is 2000 during dialysis, and the dialysis is carried out for 48 hours.
The invention also provides application of the gold nanoparticles modified based on hyaluronic acid as a nano-drug carrier in drug loading.
The invention also provides application of the nano-drug carrier based on the hyaluronic acid modified gold nanoparticles in the aspect of cell bioactivity.
Compared with the prior art, the invention has the beneficial effects that:
1) the hyaluronic acid and the polyethylene glycol are combined together, so that the water solubility and the biological performance of the medicament can be improved, and the nano material with biological targeting property is prepared, thereby realizing the targeting effect of the nano medicament;
2) according to the invention, hyaluronic acid-polyethylene glycol is modified on the surfaces of the gold nanoparticles by an effective method, so that the gold nanoparticles have better water solubility, stability and biocompatibility, and are prepared into a nano material with biological targeting and high biocompatibility, thereby realizing the function of the nano material as a nano drug carrier in the field of chemical biology;
3) the preparation method of the nano-drug carrier based on the gold nanoparticles modified by hyaluronic acid is simple and feasible, and has low cost.
Drawings
FIG. 1 is a transmission electron micrograph of mercaptopropionic acid-coated gold nanoparticles (Au @ MPA) of example 1;
FIG. 2 is a transmission electron micrograph of hyaluronic acid modified gold nanoparticle product (Au @ MPA-PEG-HA-ADH) of example 1;
FIG. 3 is a transmission electron microscopy atlas of the hyaluronic acid modified gold nanoparticles as nano-drug carrier loading Dox (Au @ MPA-PEG-HA-ADH-Dox) in example 1;
FIG. 4 is UV absorption spectra of mercaptopropionic acid coated gold nanoparticles (Au @ MPA), hyaluronic acid modified gold nanoparticles product (Au @ MPA-PEG-HA-ADH) and hyaluronic acid modified gold nanoparticles as a nano-drug carrier loaded Dox (Au @ MPA-PEG-HA-ADH-Dox) in example 1;
FIG. 5 is a transmission electron microscopy image of the hyaluronic acid modified gold nanoparticles as the nano-drug carrier loading Dox (Au @ MPA-PEG-HA-ADH-Dox) in example 2.
Detailed Description
The technical solution of the present invention is further described in detail with reference to the following examples, but the scope of the present invention is not limited thereto.
Name and model of the experimental instrument:
U.S. Perkin-Elmer Lambda-850 UV Spectrophotometer;
U.S. Perkin-Elmer Ls55 spectrofluorometer;
japanese JEOL JEM-200CX transmission electron microscope;
BioTek multifunctional microplate reader, USA.
Example 1
When the ligand is 4(PEG-HA-ADH), the synthesis steps for preparing the nano-drug carrier based on the gold nano-particles modified by the hyaluronic acid are as follows:
1) preparation of compound 4: in a 250mL round bottom flask, 1.0g of hyaluronic acid 1(HA, Mw 403.31, molecular weight, common commercial product) was dissolved in 30mL of PBS (phosphate buffered saline, pH 5.0), then 1.742g of adipic dihydrazide 2(ADH), 0.192g of 1, 2-dichloroethane (EDC) and 0.119g N-hydroxysuccinimide (NHS) were added and reacted for 24h under nitrogen protection at room temperature. After the reaction was completed, 40mg of polyethylene glycol 3(PEG, Mw 2000, common commercial product) was added and the reaction was continued for 24h under nitrogen. After the reaction is finished, filling 6mL of the mixture into a dialysis bag, adding 500mL of triple distilled water into a 500mL beaker, dropping concentrated hydrochloric acid into the triple distilled water to adjust the pH value to 6-7, putting the dialysis bag (with the molecular weight cutoff of 2000) into the triple distilled water, putting magnetons into the triple distilled water, and stirring and dialyzing the mixture for 48 hours by using a magneton stirrer (replacing the dialysis bag every 6 hours). Distilling under reduced pressure with a rotary evaporator after dialysis to obtain a compound 4 (PEG-HA-ADH);
2) preparation of compound 6: 156 μ L of 150mM HAuCl was taken4(tetrachloroauric acid) was dissolved in 80mL of triple distilled water, heated to boiling in the dark, boiled for 10min, and then added with a sodium citrate solution (obtained by dissolving 92mg of sodium citrate in 3mL of triple distilled water), stirred at boiling for 30min, and cooled to room temperature to obtain a gold solution. Centrifuging at 8000rpm for 15min to obtain gold nanoparticles (the gold nanoparticles 5 obtained by centrifuging can be dissolved in 2mL of triple distilled water, and stored in a refrigerator at 4 deg.C for use). In a 100mL round bottom flask, the gold nanoparticles 5 were uniformly dissolved in 50mL of triple distilled water, adjusted to pH 11 with 0.1M KOH, and then reacted for 2h with 3mL of 0.01M MPA (mercaptopropionic acid) ethanol solution. Centrifuging at 9000rpm for 5min to obtain compound 6Gold nanoparticles coated with mercaptopropionic acid (Au @ MPA);
3) preparation of compound product a: compound 6 (1 mg) was added to a 100mL round-bottomed flask, uniformly dissolved in 50mL of triple distilled water, and then adjusted to pH 6.5 with MES (ethanesulfonic acid, 50mM), followed by addition of EDC (7mg), NHS (10.5mg), and the reaction was stirred for 30 min. Then, 10mg of Compound 4(PEG-HA-ADH) was added thereto, and the mixture was stirred at room temperature for 24 hours. Centrifuging at 10000rpm for 5min to obtain the final product a (Au @ MPA-PEG-HA-ADH).
4) Preparation of drug-loaded compound product b: taking 6.8mg of the compound a and 5mg of doxorubicin hydrochloride (Dox), dissolving the compound a in 15mL of absolute ethanol in a 100mL round-bottom flask, reacting for 30min, then adding 50 μ L of trifluoroacetic acid, reacting at room temperature overnight under the protection of nitrogen, centrifuging at 12000rpm, collecting precipitates, and washing six times with absolute ethanol to remove unsupported Dox to obtain a final product, namely drug-loaded compound b (Au @ MPA-PEG-HA-ADH-Dox).
The particle size and the dispersion degree of the gold nanoparticles (Au @ MPA) wrapped by mercaptopropionic acid and the gold nanoparticles (Au @ MPA-PEG-HA-ADH) modified by hyaluronic acid are characterized by using a transmission electron microscope, and the results are shown in the figures 1 and 2. As can be seen in fig. 1 and 2: the modified nano gold particles have good dispersibility and are close to spherical.
The transmission electron microscope atlas of the hyaluronic acid modified nano-gold particles as the nano-drug carrier loaded with drug Dox (Au @ MPA-PEG-HA-ADH-Dox) is shown in figure 3. As can be seen in fig. 3: the hyaluronic acid modified nano gold particles are used as nano drug carriers to load Dox, then the particle size is enlarged, and a layer of film is formed on the surface of the nano gold.
The ultraviolet spectrum is used for representing the gold nanoparticles and the nano-drug carriers of the gold nanoparticles modified by hyaluronic acid before and after drug loading, and the result is shown in figure 4. As can be seen in fig. 4: the nano gold particles have an ultraviolet absorption peak at 520nm, and have an ultraviolet absorption peak at 530nm after MPA modification. The ultraviolet absorption peak of the hyaluronic acid modified nano gold particles as the nano drug carrier loaded with the drug Dox is shifted from 450nm to 480nm, which can show that the drug Dox is loaded on the nano gold particles.
Example 2
When the ligand is 7(PEG-HA), the synthesis steps for preparing the nano-drug carrier based on the gold nanoparticles modified by hyaluronic acid are as follows:
1) preparation of compound 7: in a 250mL round bottom flask, hyaluronic acid 1(HA, 1.0g) was dissolved in 30mL PBS (pH 5.0), and then PEG 3(22mg), EDC (7mg), and NHS (10.5mg) were added and reacted for 24h under nitrogen protection at room temperature. After the reaction is finished, filling 6mL of the mixture into a dialysis bag, adding 500mL of triple distilled water into a 500mL beaker, dropping concentrated hydrochloric acid into the triple distilled water to adjust the pH value to 6-7, putting the dialysis bag (the molecular weight cut-off is 2000) into the triple distilled water, putting magnetons into the triple distilled water, and stirring and dialyzing the mixture for 48 hours by using a magneton stirrer (the dialysate is replaced every 6 hours). Carrying out reduced pressure distillation by using a rotary evaporator after dialysis to obtain a compound 7 (PEG-HA);
2) preparation of compound 6: reference example 1;
3) preparation of a product a: compound 6 (1 mg) was added to a 100mL round-bottomed flask, uniformly dissolved in 50mL of triple distilled water, and then adjusted to pH 6.5 with MES (ethanesulfonic acid, 50mM), followed by addition of EDC (7mg) and NHS (10.5mg) and stirring for reaction for 30 min. Then 10mg of Compound 7(PEG-HA) was added and stirred at room temperature for 24 h. Centrifuging at 10000rpm for 5min to obtain the final product a (Au @ MPA-PEG-HA).
4) Preparation of drug-loaded compound product b (Au @ MPA-PEG-HA-Dox): refer to example 1.
The particle size and the dispersion degree of the hyaluronic acid modified gold nanoparticles as the nano-drug carrier loaded with drug Dox are characterized by using a transmission electron microscope, and the result is shown in fig. 5. As can be seen in fig. 5: the hyaluronic acid modified gold nanoparticles are used as a nano-drug carrier to load a drug Dox, so that the particle size is enlarged, and the dispersion is uniform and close to a sphere.
Activity assay
Cell culture: HL-7702 (human liver cell), HeLa (cervical cancer cell), HepG2 (liver cancer cell) and HCT-116 (human colorectal adenocarcinoma cell), the cells were cultured with 1640 medium containing 10% (v/v) fetal bovine serum and 1% (v/v) streptomycin mixture in a culture flaskAnd (5) culturing. The culture flask is placed at 37 ℃ and contains 5% CO2And the cultivation was carried out in an incubator with a humidity of 90%.
Cytotoxicity test: cytotoxicity of the nano-drug carrier a of hyaluronic acid-modified gold nanoparticles and the drug-loaded product b prepared in examples 1 to 2 in HepG2, HL-7702, HeLa and HCT-116 cells was measured by MTT method: after subculturing the cells for 3 or 4 times, when the cells grow to logarithmic phase, digesting the cells with 0.25% trypsin to form single cell suspension, counting the viable cells by adopting a blood counting chamber, and adjusting the concentration of the viable cells to 5 × 104Perml/mL in 96-well plates, 100. mu.L per well, 5% CO at 37 ℃2And cultured in an incubator with a humidity of 90% for 24 hours, the old medium was aspirated, and samples of products a and b prepared in examples 1 and 2 were added at different concentrations diluted with the medium, respectively. The 96-well plate after the addition of the sample was placed at 37 ℃ with 5% CO2The culture box is incubated for 48 hours, then MTT 20 mu L/well (2.5mg/mL) is added, the supernatant is discarded after 4 hours, DMSO 100 mu L/well is added, the oscillation is carried out for about 10min, the OD value is measured by an M200 microplate reader, and the wavelength is set to be 570nm and 690 nm. The cell viability of the wells to which no sample was added was set as a control to 100%, and the cell viability was calculated to evaluate the cytotoxicity of the samples. The results are shown in Table 1 below.
TABLE 1 cytotoxicity of the products and intermediates prepared in examples 1 to 2
Table 1 shows the in vitro growth inhibitory activity of the nano-drug carrier a of hyaluronic acid-modified gold nanoparticles and the drug-loaded product b prepared in examples 1 to 2 on HepG2, HeLa, HCT-116 and HL-7702 cells. IC (integrated circuit)50The value is the sample concentration value (. mu.g/mL), IC, at which the number of cells capable of normal division growth is suppressed to a level of 50%50The larger the valueIndicating that the sample is less cytotoxic. The experimental results show that: the nano-drug carrier a based on the gold nano-particles modified by the hyaluronic acid HAs lower toxicity to cells, and the product b after drug loading HAs strong inhibition effect on tumor cells and better inhibition activity on HCT-116 cells and HepG2 cells, because the surfaces of HTC-116 and HepG2 cells have more CD44 expression receptors, HA can specifically identify the receptors, and the inhibition activity of HA on normal liver cells HL-7702 is lower, which indicates that the HA HAs certain cancer cell selectivity.
To sum up, the following steps are carried out: the nano-drug carrier a of the gold nanoparticles modified by hyaluronic acid can be used as a nano-drug carrier, is applied to the field of chemical biology, and can lay a foundation for better designing the nano-drug carrier.
Claims (5)
1. A gold nanoparticle based on hyaluronic acid modification is characterized in that the structural formula is as follows:
au is mercaptopropionic acid modified gold nanoparticles.
2. The method for preparing gold nanoparticles based on hyaluronic acid modification according to claim 1, comprising the following steps:
1) preparation of compound 4 or 7:
dissolving Hyaluronic Acid (HA) in PBS (phosphate buffer solution), adding Adipic Dihydrazide (ADH), 1, 2-dichloroethane (EDC) and N-hydroxysuccinimide (NHS), reacting for 20-30h under the condition of room temperature and nitrogen protection, and after the reaction is finished, adding polyethylene glycol (PEG) and continuing to react for 20-30h under the nitrogen protection; after the reaction is finished, obtaining a PEG-HA-ADH compound 4 through dialysis and reduced pressure distillation;
or dissolving Hyaluronic Acid (HA) in PBS, adding polyethylene glycol (PEG), 1, 2-dichloroethane (EDC) and N-hydroxysuccinimide (NHS), reacting for 20-30h at room temperature under the protection of nitrogen, and dialyzing and distilling under reduced pressure to obtain a PEG-HA compound 7 after the reaction is finished;
2) preparation of compound 6: dissolving tetrachloroauric acid in the triple distilled water, heating to boil away from light, adding sodium citrate solution after boiling for 10-20min, stirring for 30-50min under boiling state, cooling to room temperature to obtain gold solution, and centrifuging to obtain nano gold particles; uniformly dissolving the gold nanoparticles in triple distilled water, adjusting the pH value to 10-12, adding an ethanol solution of mercaptopropionic acid, reacting for 2-3h, and centrifuging to obtain a compound 6, namely gold nanoparticles wrapped by mercaptopropionic acid;
3) uniformly dissolving the compound 6 in triple distilled water, adjusting the pH to 6-7 by using ethanesulfonic acid, then adding 1, 2-dichloroethane (EDC) and N-hydroxysuccinimide (NHS), and stirring for reacting for 30-50 min; then adding the compound 4 or 7, stirring for 20-30h at room temperature, and centrifuging to obtain the compound.
3. The method for preparing gold nanoparticles based on hyaluronic acid modification according to claim 2, wherein the mass ratio of compound 6 to compound 4 or 7 is 1: 10.
4. the method for preparing gold nanoparticles based on hyaluronic acid modification according to claim 2, wherein in step 1), the cut-off molecular weight of a dialysis bag is 2000 during dialysis, and the dialysis is performed for 48 hours.
5. The use of the gold nanoparticles based on hyaluronic acid modification as claimed in claim 1 as a nano-drug carrier for drug loading.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113230415A (en) * | 2021-05-18 | 2021-08-10 | 南华大学 | Fucose and cyclodextrin modified polypeptide targeted atherosclerosis-related macrophage nano-carrier system and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120058321A (en) * | 2010-11-29 | 2012-06-07 | 연세대학교 산학협력단 | HA-PEG-Gold CT image contrast agent for enhancing residence time and absorption |
| CN105860960A (en) * | 2016-04-20 | 2016-08-17 | 河南大学 | Cytomembrane fluorescence probe based on gold nanoparticle, preparation method and application of cytomembrane fluorescence probe |
| CN105999283A (en) * | 2016-05-05 | 2016-10-12 | 东华大学 | Preparation method for adriamycin-loaded polyethyleneimine-hyaluronic acid-modified hectorite-coated gold nanoparticles |
| CN106975755A (en) * | 2017-03-27 | 2017-07-25 | 广西师范大学 | A kind of hyaluronic acid decorated golden nanometer particle aggregation HA Cys AuNPs of water solubility and preparation method |
| KR20200015037A (en) * | 2018-08-02 | 2020-02-12 | 가천대학교 산학협력단 | A photothermal nanocomplex comprising photothermal nanoparticle, anticancer drug and conjugate of hyaluronic acid and PEG |
-
2020
- 2020-11-18 CN CN202011291708.9A patent/CN112386705A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120058321A (en) * | 2010-11-29 | 2012-06-07 | 연세대학교 산학협력단 | HA-PEG-Gold CT image contrast agent for enhancing residence time and absorption |
| CN105860960A (en) * | 2016-04-20 | 2016-08-17 | 河南大学 | Cytomembrane fluorescence probe based on gold nanoparticle, preparation method and application of cytomembrane fluorescence probe |
| CN105999283A (en) * | 2016-05-05 | 2016-10-12 | 东华大学 | Preparation method for adriamycin-loaded polyethyleneimine-hyaluronic acid-modified hectorite-coated gold nanoparticles |
| CN106975755A (en) * | 2017-03-27 | 2017-07-25 | 广西师范大学 | A kind of hyaluronic acid decorated golden nanometer particle aggregation HA Cys AuNPs of water solubility and preparation method |
| KR20200015037A (en) * | 2018-08-02 | 2020-02-12 | 가천대학교 산학협력단 | A photothermal nanocomplex comprising photothermal nanoparticle, anticancer drug and conjugate of hyaluronic acid and PEG |
Non-Patent Citations (1)
| Title |
|---|
| 蔡中超: "纳米金载药体系的设计合成及其生物活性研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113230415A (en) * | 2021-05-18 | 2021-08-10 | 南华大学 | Fucose and cyclodextrin modified polypeptide targeted atherosclerosis-related macrophage nano-carrier system and preparation method and application thereof |
| CN113230415B (en) * | 2021-05-18 | 2022-04-12 | 南华大学 | Fucose and cyclodextrin modified polypeptide targeted atherosclerosis-related macrophage nano-carrier system and preparation method and application thereof |
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