CN102627826A - Gold nanoparticle with core-shell structure and preparation method thereof - Google Patents

Abstract

The invention provides a gold nanoparticle with a core-shell structure and a preparation method thereof. The method comprises the following steps of: directly performing aminolysis on a dithioester at the tail end of a poly(glycol-segmented-N-isopropylacrylamide) copolymer of which the tail end is provided with a dithioester group to obtain a monothiol-terminated poly (glycol-segmented-N-isopropylacrylamide) copolymer; and performing ligand interchange reaction on the monothiol-terminated poly (glycol-segmented-N-isopropylacrylamide) copolymer and the gold nanoparticle with sodium citrate as a ligand, and grafting a segmented copolymer onto the surface of the gold nanoparticle to obtain the gold nanoparticle with the core-shell structure, wherein the shell of the gold nanoparticle is poly(glycol-segmented-N-isopropylacrylamide) copolymer (PEG-B-PNIPAM). Compared with the prior art, the outer layer of the block polymer has high solubility, so the formed gold nanoparticle with the core-shell structure also has high solubility. Due to the block PEG on the outer layer, the stability of the gold nanoparticle with the core-shell structure is also improved, and the aggregation among nanoparticles is inhibited.

Description

A kind of gold nanoparticle with core-shell structure and preparation method thereof

technical field

The invention belongs to the technical field of nanomaterials, and in particular relates to a gold nanoparticle with a core-shell structure and a preparation method thereof.

Background technique

Core-shell materials generally consist of a central core and an outer shell. Through the core-shell composite method, on the one hand, the originally unstable or less stable core can be stabilized, and on the other hand, functions and properties that the core and shell materials do not have can be obtained, or new forms of substance can be obtained.

In recent years, gold nanoparticles with core-shell structure have attracted extensive attention due to their potential applications in optoelectronics, biomedicine, and smart sensing. Gold nanoparticles with core-shell structure are divided into gold nanoparticles protected by a single layer of organic small molecules and gold nanoparticles protected by polymers. Compared with the former, gold nanoparticles protected by polymers have more advantages, such as: polymer complex The body can endow gold nanoparticles with good stability, processability, biocompatibility and environmental responsiveness.

Generally, there are two main methods for preparing polymer-protected gold nanoparticles, namely "graft from" and "graft to". "Graft from" mainly uses the method of surface-initiated polymerization to make monomers aggregate and grow on the surface of gold particles. For example, Li et al. obtained temperature-responsive core-shell gold nanoparticles through the "graft from" method, but this method Not only does it need to synthesize an initiator for ligand exchange with nanoparticles and also as an initiator for initiating polymerization, but also requires the use of highly toxic ligands and catalysts, and the polymerization process itself is cumbersome. "Graft to" is mainly to directly bond polymers to the surface of gold nanoparticles. For example, Tenhu et al. prepared temperature-responsive core-shell structure gold nanoparticles in situ through the "graft to" method. The preparation process is simple and at the same time The molecular weight of the polymer can be controlled as expected, but the size of the nanoparticles cannot be well controlled by the in situ reduction, and the size distribution of the obtained gold nanoparticles is relatively wide.

At present, Zhu et al. have improved the preparation method of Tenhu et al., using the "graft to" method, by exchanging a temperature-responsive polymer with a thiol group at the end and a pre-synthesized gold nanoparticle to obtain a temperature Responsive core-shell structure gold nanoparticles overcome the shortcomings of the in situ preparation method, but since this method only protects the gold nanoparticles through the homopolymeric polymer (PNIPAM), there are no other stability factors, so the prepared core Shell-structured gold nanoparticles tend to aggregate under relatively high temperature conditions, and their stability and solubility are poor.

Contents of the invention

In view of this, the technical problem to be solved in the present invention is to provide a core-shell structure gold nanoparticle and its preparation method, the core-shell structure gold nanoparticle prepared by the method has temperature responsiveness and also has good stability and solubility .

The invention provides a gold nanoparticle with a core-shell structure, which is composed of an inner core and an outer shell, the inner core is a gold nano particle, and the outer shell is a poly(ethylene glycol-block-N-isopropylacrylamide) copolymer.

The invention provides a method for preparing gold nanoparticles with a core-shell structure, comprising the following steps:

A) The poly(ethylene glycol-block-N-isopropylacrylamide) copolymer with a dithioester group at the end is subjected to an amination reaction with an aminolysis reagent to obtain a monothiol-terminated poly(ethylene glycol- Block-N-isopropylacryloyl) block copolymer;

B) Carrying out ligand exchange reaction between the poly(ethylene glycol-block-N-isopropylacrylamide) copolymer terminated by monomercapto and gold nanoparticles with sodium citrate as a ligand to obtain a core-shell structure Gold Nanoparticles.

Preferably, the poly(ethylene glycol-block-N-isopropylacrylamide) copolymer with a dithioester group at the end is prepared according to the following method:

S1) performing an addition reaction of monomethyl-terminated polyethylene glycol and maleic anhydride to obtain an addition product;

S2) reacting the addition product with dithiobenzoic acid to obtain a macromolecular chain transfer agent based on monomethyl-terminated polyethylene glycol;

S3) React the macromolecular chain transfer agent based on monomethyl-terminated polyethylene glycol, azobisisobutyronitrile and N-isopropylacrylamide to obtain poly(ethylene glycol) with a dithioester group at the end diol-block-N-isopropylacrylamide) copolymer.

Preferably, the reaction temperature condition of step S3 is 60-80°C.

Preferably, the aminolysis reagent in the step A is a short-chain aliphatic aminoalkane.

Preferably, the short-chain aliphatic aminoalkane is one or more of ethylamine, propylamine, isopropylamine and tert-butylamine.

Preferably, tetrahydrofuran (THF), dimethylformamide (DMF) or dichloromethane is used as the reaction solvent for the amination reaction in the step A.

Preferably, the aminolysis reaction and the ligand exchange reaction are respectively carried out under anaerobic conditions.

Preferably, the reaction time of the aminolysis reaction is 20-30 hours.

Preferably, the reaction time of the ligand exchange reaction in the step B is 60-80 h.

The invention provides a core-shell structure gold nanoparticle and a preparation method thereof. The method comprises dithioester at the end of poly(ethylene glycol-block-N-isopropylacrylamide) copolymer (PEG-b-PNIPAM) Direct aminolysis is thiol, and obtains poly(ethylene glycol-block-N-isopropylacrylamide) copolymer (PEG-b-PNIPAM-SH) end-capped by monothiol; further with sodium citrate as ligand The gold nanoparticles were subjected to ligand exchange reaction, and the block copolymer was grafted onto the surface of the gold nanoparticles to obtain a core-shell structure gold shell with a poly(ethylene glycol-block-N-isopropylacrylamide) copolymer. Nanoparticles. Compared with the gold nanoparticles protected by homopolymerized polymers in the prior art, PEG-b-PNIPAM is used as the shell to protect the gold nanoparticles in the present invention. First, the solubility of the outer block is very good, so the formed Core-shell gold nanoparticles also have good solubility. Secondly, the presence of the outer block PEG also provides a layer of protection for the core-shell structured gold nanoparticles, which improves the stability of the core-shell structured gold nanoparticles and inhibits the aggregation between nanoparticles. Thirdly, the solubility of the inner block PNIPAM changes with temperature, thus endowing the core-shell gold nanoparticles with temperature responsiveness.

The experimental results show that the average hydrodynamic radius (R _h ) of the gold nanoparticles with core-shell structure prepared by the present invention decreases with the increase of temperature, the _Rh is about 26.5nm at 25°C, and the _Rh is about 23nm at 50°C , with good temperature responsiveness. At the same time, the core-shell structure gold nanoparticles prepared by the method do not aggregate in the temperature range of 15-55 DEG C, and have good stability.

Description of drawings

Fig. 1 is the transmission electron micrograph of the gold nanoparticle with sodium citrate as ligand prepared in Example 1 of the present invention;

FIG. 2 is a transmission electron micrograph of gold nanoparticles with a core-shell structure prepared in Example 1 of the present invention.

Detailed ways

The invention provides a method for preparing gold nanoparticles with a core-shell structure, comprising the following steps: A) poly(ethylene glycol-block-N-isopropylacrylamide) copolymer with a dithioester group at the end (PEG-b-PNIPAM) undergoes an aminolysis reaction with an aminolysis reagent to obtain a monomercapto-terminated poly(ethylene glycol-block-N-isopropylacrylamide) copolymer (PEG-b-PNIPAM-SH); B) Carrying out ligand exchange reaction between the poly(ethylene glycol-block-N-isopropylacrylamide) copolymer terminated by monomercapto and gold nanoparticles with sodium citrate as a ligand to obtain a core-shell structure Gold Nanoparticles.

Wherein, the PEG-b-PNIPAM is preferably prepared according to the reversible addition-fragmentation chain transfer (RAFT) method:

S1) Add monomethyl-terminated polyethylene glycol (mPEG-OH) and dry toluene solution into a container, under nitrogen protection, heat until mPEG-OH is completely dissolved, then add maleic anhydride (MAh), and react overnight. Toluene was removed under reduced pressure, redissolved in dichloromethane, precipitated in ether to remove excess MAh, and dried in vacuo to give the addition product (mPEG-MAh). In order to completely react mPEG-OH, MAh is preferably in excess, and the mass ratio of mPEG-OH to MAh is more preferably 6:1-10:1, most preferably 8:1.

S2) react the addition product mPEG-MAh with dithiobenzoic acid (DTBA) and dry carbon tetrachloride for 20-24 hours at 60-70° C. after airtight degassing, and add part of dichloromethane after the reaction is completed, And precipitate in ether, repeat this process until the excess DTBA is completely removed, and vacuum-dry at 35-45°C to obtain a macromolecular chain transfer agent (mPEG-CTA) based on monomethyl-terminated polyethylene glycol. The reaction temperature is preferably 65°C, the reaction time is preferably 24h, and the vacuum drying temperature is preferably 40°C.

S3) adding the mPEG-CTA, azobisisobutyronitrile, N-isopropylacrylamide (NIPAM) and dry acetonitrile solution into a container, and subjecting the reaction mixture to a freezing-thawing degassing process, and vacuum sealing, React at 55-80°C for 20-24 hours, and the obtained product is precipitated with ether, and dried in vacuum at 40-55°C to obtain poly(ethylene glycol-block-N-isopropylacrylamide) with a dithioester group at the end ) copolymer (PEG-b-PNIPAM). The reaction temperature is preferably 60-80°C, more preferably 80°C, the reaction time is preferably 24 hours, and the vacuum drying temperature is preferably 50°C.

The present invention uses PEG-b-PNIPAM as the outer shell to protect the gold nanoparticles. Firstly, the outer block has good solubility, so the core-shell structure gold nanoparticles formed by it also have good solubility. Secondly, the presence of the outer block PEG also provides a layer of protection for the core-shell structured gold nanoparticles, which improves the stability of the core-shell structured gold nanoparticles and inhibits the aggregation between nanoparticles. Thirdly, the solubility of the inner block PNIPAM changes with temperature, thus endowing the core-shell gold nanoparticles with temperature responsiveness.

In order to clearly illustrate the present invention, the experimental processes of step A and step B are described in detail below respectively.

According to the present invention, the step A specifically includes: adding PEG-b-PNIPAM into a container containing a reaction solvent, removing oxygen from the reaction solution through freezing-thawing and degassing, adding an aminolysis reagent under nitrogen protection, After the container is sealed in vacuum, react at room temperature for 20-30 hours, preferably 24 hours, and the obtained product is precipitated with ether, and the vacuum drying temperature is 30-50°C, preferably 40°C.

Wherein, the aminolysis reagent in the step A is preferably a short-chain aliphatic aminoalkane, more preferably one or more of ethylamine, propylamine, isopropylamine and tert-butylamine, most preferably propylamine and isopropylamine. The reaction solvent of the aminolysis reaction is preferably THF, DMF or dichloromethane, more preferably THF or dichloromethane.

According to the present invention, the step B specifically includes: adding PEG-b-PNIPAM-SH into a container containing deionized water, freezing-thawing and degassing the reaction solution, adding citric acid under nitrogen protection and vigorous stirring Gold nanoparticles with sodium as a ligand are reacted at room temperature for 60-80 hours, preferably 72 hours, and then centrifuged at 10000-15000 r/min for 1-3 hours at low temperature, preferably at 5 °C, preferably at a speed of 11000 r/min, centrifuged The time is preferably 2 hours, and the supernatant is removed after centrifugation, and this process is repeated several times until the unreacted polymer is completely removed, preferably three times.

Among them, in step A and step B, in order to prevent the disulfide reaction between the generated block copolymers containing mercapto groups, which will affect the ligand exchange reaction, it is necessary to control the system to be absolutely free of oxygen.

The average hydrodynamic radius (R _h ) of the core-shell structure gold nanoparticles prepared by the present invention decreases with the increase of temperature. At 25°C, _Rh is about 26.5nm, and at 50°C, _Rh is about 23nm, which has good temperature responsiveness. At the same time, the core-shell structure gold nanoparticles prepared by the method do not aggregate in the temperature range of 15-55 DEG C, and have good stability.

In order to further illustrate the present invention, a method for preparing gold nanoparticles with a core-shell structure provided by the present invention will be described in detail below in conjunction with examples.

All reagents used in the following examples are commercially available.

Example 1

1.1 Synthesis of dithiobenzoic acid (DTBA)

Add 22.5g of 30% sodium methoxide solution, 4g of dry sulfur powder into a 250mL three-neck round bottom flask equipped with a stirring bar, a constant pressure dropping funnel and a spherical condenser, and slowly add 7.95 g benzyl, react at room temperature for 30 minutes after completion, then raise the temperature to 70°C and react overnight. After cooling in an ice-water bath, the insoluble matter was filtered off, and the solvent was removed under reduced pressure. The residue was re-dissolved in water, acidified by adding ether and 1.0mol/L hydrochloric acid to convert it into DTBA. Repeated extraction three times with iced sodium hydroxide solution and hydrochloric acid/ether solution, and finally obtained 6.6 g of pure red oily liquid as DTBA, with a yield of about 60%.

1.2 Addition reaction of mPEG-OH with MAh

Add 8.0g mPEG-OH and 30mL dry toluene solution into a 100mL round bottom flask, under nitrogen protection, heat to 70°C to completely dissolve mPEG-OH, then quickly add 1.0g MAh and react overnight. Toluene was removed under reduced pressure, and then the reactant was redissolved in dichloromethane, precipitated in ether, and this process was repeated three times until the excess MAh was completely removed, and vacuum-dried at 50°C for two days to obtain the white product mPEG-MAh.

1.3 Synthesis of mPEG-CTA

Add 1.0 g of mPEG-MAh obtained in step 1.2, 0.64 g of DTBA obtained in step 1.1 and 2 mL of dry carbon tetrachloride to a polymerization tube equipped with a stirring bar, and react at 65°C for 24 h after sealing and degassing. After the reaction was completed, part of dichloromethane was added and precipitated in ether. This process was repeated three times until the excess DTBA was completely removed. After vacuum drying at 40°C for two days, the light red macromolecular chain transfer agent mPEG-CTA was obtained.

1.4 Synthesis of PEG-b-PNIPAM

Add 1.0 mg of azobisisobutyronitrile, 0.80 g of NIPAM, 0.20 g of the macromolecular chain transfer agent mPEG-CTA prepared in step 1.3 and 5.5 mL of dry acetonitrile solution into a polymerization tube equipped with a stirring bar. After the reaction mixture was subjected to three freeze-thaw degassing processes, the tube was sealed under vacuum and reacted at 80° C. for 24 h. The obtained product was precipitated three times with ether, and dried in vacuum at 50° C. for two days to obtain PEG-b-PNIPAM with a monomer conversion rate of about 50%.

1.5 Amination reaction of block copolymer terminal

Add 0.20 g of PEG-b-PNIPAM prepared in step 1.4 into a polymerization tube containing 8.0 mL of THF solvent, freeze-thaw the reaction solution for three times, and add 0.020 g of propylamine quickly under the protection of nitrogen, and the solution The color quickly changed from light red to nearly colorless, and then the reaction mixture was frozen-thawed and degassed three times, vacuum-sealed, and reacted at room temperature for 24 hours. The decomposed product PEG-b-PNIPAM-SH has a yield of about 98%.

1.6 Preparation of gold nanoparticles with sodium citrate as ligand

Add 0.0206 g of tetrachloroauric acid tetrahydrate and 50 mL of deionized water into a 100 mL round bottom flask equipped with a stirring bar. Vigorously stir and heat to boiling reflux, quickly add 5mL (33.8mmol/L) sodium citrate aqueous solution, the color of the solution changes from dark yellow to wine red, after boiling for 10min, remove the heat, continue stirring for 15min, after cooling, get citric acid Sodium-liganded gold nanoparticles. Its particle size is about 12±1nm.

1.7 Preparation of temperature-responsive core-shell gold nanoparticles

Add 0.050g of PEG-b-PNIPAM-SH prepared in step 1.5 to a polymerization bottle filled with 20mL of deionized water, then freeze-thaw the reaction liquid for three times to degas, and quickly add 0.4mL 1mmol/L gold nanoparticle solution with sodium citrate as a ligand prepared in step 1.6, react at room temperature for 72h, then centrifuge at 5°C for 2h at a speed of 11000r/min, remove the supernatant, repeat This process was repeated three times until unreacted polymer was completely removed. Finally, the purified core-shell gold nanoparticles were dispersed in deionized water.

The following is the reaction formula of each step:

a. Synthesis of dithiobenzoic acid (DTBA)

b. Addition reaction of mPEG-OH with maleic anhydride (MAh)

c. Synthesis of macromolecular chain transfer agent (mPEG-CTA)

d. Synthesis of block copolymer (PEG-b-PNIPAM)

e. Amination reaction of block copolymer terminal (PEG-b-PNIPAM-SH)

f. Preparation of gold nanoparticles (Au NPs)

g. Preparation of temperature-responsive core-shell gold nanoparticles

The gold nanoparticles with sodium citrate as a ligand obtained in 1.6 and the core-shell structure gold nanoparticles obtained in 1.7 were analyzed by the method of transmission electron microscopy, and the transmission electron microscope photos of gold nanoparticles before and after ligand exchange were obtained, respectively as follows Figure 1 and Figure 2 show. By analyzing and comparing electron micrographs, it can be seen that the dispersion of gold nanoparticles is improved due to the existence of the nanoparticle polymer shell.

Using X-ray energy dispersive spectroscopy, the elemental analysis of the core-shell structure gold nanoparticles obtained in 1.7 proves that there are Au, C, N, O and S elements in the obtained product, because the polymer shell is grafted through the terminal mercapto group With the surface of gold nanoparticles, and C, N, O, S are the constituent elements of the block copolymer PEG-b-PNIPAM, confirming the existence of the polymer shell.

The temperature response test results show that the average hydrodynamic radius R _h of the core-shell gold nanoparticles decreases with the increase of temperature. The _Rh is about 26.5 nm at 25 ° _C and about 23 nm at 50 °C. It is mainly caused by the change of the solubility of the block PNIPAM in the inner layer with temperature: as the temperature increases, the solubility of PNIPAM in water decreases, dehydration occurs, and the polymer in the inner layer gradually begins to collapse. Shrinkage caused a decrease in _Rh of the entire core-shell structured gold nanoparticles.

Through the stability test, the results show that no aggregation occurs within the range of 15-55°C. This is mainly due to the fact that the presence of the outer block PEG inhibits the aggregation between nanoparticles.

From the above experimental results, it can be seen that the present invention introduces the environment-influenced block copolymer into the gold nanoparticle system, which not only increases the stability and solubility of the nanoparticles, but also endows the gold nanoparticles with temperature responsiveness.

Example 2

Prepare each intermediate and final product in the same manner as in Example 1, only block copolymer PEG-b-PNIPAM is synthesized as follows:

Add 1.0 mg of azobisisobutyronitrile, 0.80 g of NIPAM, 0.20 g of the mPEG-CAT obtained in 1.4 and 5.5 mL of dry acetonitrile solution into a polymerization tube equipped with a stirring bar, and freeze-thaw the reaction mixture three times. Gas process, seal the tube under vacuum, and react at 60°C for 24h. The obtained product was precipitated three times with ether, and dried in vacuum at 50° C. for two days to obtain a block copolymer PEG-b-PNIPAM with a monomer conversion rate of about 30%.

Example 3

Prepare each intermediate and final product in the same manner as in Example 1, only the aminolysis reaction at the end of the block copolymer is as follows:

1.0g of PEG-b-PNIPAM obtained in 1.5 was added to a polymerization tube containing 10mL of dichloromethane solvent, the reaction solution was frozen-thawed and degassed three times, and 0.11g of propylamine was added quickly under the protection of nitrogen, and the color of the solution changed from The light red color quickly changed to nearly colorless, and then the reaction mixture was frozen-thawed and degassed three times, sealed in vacuum, and reacted at room temperature for 24 hours. The obtained product was precipitated three times with diethyl ether and dried in vacuum at 40° C. for two days to obtain the product PEG-b-PNIPAM-SH after aminolysis with a yield of about 98%.

Example 4

Prepare each intermediate and final product in the same manner as in Example 1, only the aminolysis reaction at the end of the block copolymer is as follows:

Add 1.0g of PEG-b-PNIPAM to a polymerization tube containing 10mL of dichloromethane solvent, freeze-thaw the reaction solution for three times, and add 0.12g of isopropylamine quickly under the protection of nitrogen, the color of the solution changes from light to light The red color quickly changed to nearly colorless, and the reaction mixture was frozen-thawed and degassed three times, sealed in vacuum, and reacted at room temperature for 24 hours. The obtained product was precipitated three times with ether, and dried in vacuum at 40° C. for two days to obtain the product PEG-b-PNIPAM-SH after aminolysis, with a yield of about 98%.

The above is only a preferred embodiment of the present invention, it should be pointed out that, for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications can also be made. It should be regarded as the protection scope of the present invention.

Claims (10)

1. a nucleocapsid structure golden nanometer particle is made up of kernel and shell, it is characterized in that, said kernel is a golden nanometer particle, and shell is for gathering (terepthaloyl moietie-block-N-NSC 11448) multipolymer.

2. the preparation method of a nucleocapsid structure golden nanometer particle is characterized in that, may further comprise the steps:

A) with end have two thioester substrates gather (terepthaloyl moietie-block-N-NSC 11448) multipolymer and aminolysis reagent carries out aminolysis reaction, obtain that single sulfydryl is end capped to gather (terepthaloyl moietie-block-N-NSC 11448) multipolymer;

B) with said end capped gathering of single sulfydryl (terepthaloyl moietie-block-N-NSC 11448) multipolymer carry out ligand exchange reaction with the golden nanometer particle that with the Trisodium Citrate is part, obtain the nucleocapsid structure golden nanometer particle.

3. preparation method according to claim 2 is characterized in that, (terepthaloyl moietie-block-N-NSC 11448) multipolymer that gathers that said end has two thioester substrates prepares according to following method:

S1) end capped polyoxyethylene glycol of monomethyl and MALEIC ANHYDRIDE are carried out addition reaction, obtain adduct;

S2) with said adduct and dithiobenzoic acid reaction, obtain macromolecular chain transfer agent based on the end capped polyoxyethylene glycol of monomethyl;

S3) with said macromolecular chain transfer agent based on the end capped polyoxyethylene glycol of monomethyl, Diisopropyl azodicarboxylate and the reaction of N-NSC 11448, what obtain that end has two thioester substrates gathers (terepthaloyl moietie-block-N-NSC 11448) multipolymer.

4. preparation method according to claim 3 is characterized in that, said step S3) temperature of reaction be 60～80 ℃.

5. preparation method according to claim 2 is characterized in that, said aminolysis reagent is short-chain fat family amido alkane.

6. preparation method according to claim 5 is characterized in that, said short-chain fat family amido alkane is one or more in ethamine, propylamine, Isopropylamine and the TERTIARY BUTYL AMINE.

7. preparation method according to claim 2 is characterized in that, said aminolysis reaction is with THF, and N or methylene dichloride are reaction solvent.

8. preparation method according to claim 2 is characterized in that said aminolysis reaction and ligand exchange reaction carry out respectively under oxygen free condition.

9. preparation method according to claim 2 is characterized in that, the reaction times of said aminolysis reaction is 20～30h.

10. preparation method according to claim 2 is characterized in that, the reaction times of said ligand exchange reaction is 60～80h.

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