CN102895664B - Gadolinium stabilizing amorphous calcium carbonate nanocomposite material and preparation method - Google Patents

Abstract

The invention discloses an ACC-Gd multifunctional nanomaterial obtained by stabilizing amorphous calcium carbonate (ACC) with the element gadolinium (Gd), its preparation method and application, and a method of obtaining the ACC-Gd nanomaterial in the aforementioned ACC-Gd nanomaterial ACC-Gd-polymer multifunctional nanomaterials obtained by introducing suitable polymers or biomacromolecules, as well as preparation methods and applications thereof. The present invention obtains novel multifunctional nanomaterials by stabilizing amorphous calcium carbonate ACC with Gd, and, because Gd is in the crystal lattice of amorphous calcium carbonate, greatly reduces the toxicity of Gd itself, simultaneously as the Gd of magnetic element has Good contrast effect, so the multifunctional nanomaterial of the present invention can be used as MRI contrast agent.

Description

A gadolinium-stabilized amorphous calcium carbonate nanocomposite material and preparation method thereof

technical field

The invention relates to multifunctional nanomaterials, more particularly to a novel stabilized amorphous calcium carbonate (ACC) multifunctional nanomaterial.

Background technique

At present, the following research reports on stable ACC can be seen:

The United Kingdom (CrystEngComm (Crystal Engineering Communication), 2011, Volume 13, pages 952-956) reported a method for Mg to stabilize ACC, and did related research on the mineralization of ACC induced by Mg.

Germany (Advanced Materials (Advanced Materials), 1996, Volume 8, Page 222 to 226) discovered the stabilizing effect of biological macromolecules on ACC, studied the content of various amino acids in natural ACC, and the content of glycine and serine in ACC Accounting for a large proportion, however, aspartic acid accounts for the largest proportion in crystalline calcium carbonate. The journal reported on page 2217 of volume 17 in 2005 that ACC was stabilized with phytic acid to obtain a hollow spherical structure. However, the particle size of the obtained ACC is too large, which can only be limited to the research on the mineralization mechanism, and is not suitable for biological applications.

The Netherlands (Journal of Crystal Growth (Journal of Crystal Growth), 2008, Volume 310, pages 3779 to 3787) reported the stabilization of polymer polyacrylic acid (PAA) and polystyrene sodium sulfonate (PSS) to ACC, and in alcohol For the stability time in the water system, only some simple mechanism studies have been done, and no applied research has been done, and the stability time of this method in the alcohol-water system is relatively short, which cannot be adapted to many biological applications.

All of the above ACC studies have focused on the mineralization mechanism, and have not combined the traditional mineralization material of calcium carbonate with biomedical applications. In particular, they have not mentioned the use of the magnetic element gadolinium (Gd) to stabilize ACC to obtain multifunctional nanomaterials with broad biomedical applications.

Contents of the invention

The purpose of the present invention is to provide a kind of magnetic element gadolinium (Gd) to stabilize amorphous calcium carbonate (ACC) to obtain novel multifunctional nanometer material.

In one aspect, the present invention provides a multifunctional nanomaterial obtained by stabilizing amorphous calcium carbonate (ACC) with the element gadolinium (Gd) (also referred to as "ACC-Gd multifunctional nanomaterial").

In another aspect, the present invention provides a multifunctional nanomaterial obtained by introducing a suitable polymer or biomacromolecule into the above-mentioned ACC-Gd nanomaterial (herein referred to as "ACC-Gd-polymer nanomaterial") ).

In a preferred embodiment, the polymer or biomacromolecule is one or more selected from PAA, PSS and water-soluble amino acids.

In another aspect, the present invention provides a method for preparing the above-mentioned ACC-Gd multifunctional nanomaterial, the method comprising introducing Gd into ACC to stabilize ACC, thereby obtaining the ACC-Gd multifunctional nanomaterial Material. .

In a preferred embodiment, calcium (Ca) salt solution and Gd salt solution are first mixed, then carbonate solution is added, reacted under vigorous stirring, filtered and dried to obtain the ACC-Gd multifunctional nanomaterial.

In a preferred embodiment, equal volumes and equal concentrations of said Ca salt solution and said carbonate solution are used.

In a preferred embodiment, the concentration of the Ca salt solution and the carbonate solution used is 0.1M-0.5M.

In a preferred embodiment, the Ca salt solution is a CaCl ₂ solution, the Gd salt solution is a GdCl ₃ solution, and the carbonate solution is a Na ₂ CO ₃ solution.

In a preferred embodiment, the molar ratio of the Ca salt solution and the Gd salt solution is [Ca ²⁺ ]/[Gd ³⁺ ]=1-10, that is, [Gd ³⁺ ]/[Ca ²⁺ ]=1/10-1 amount is used.

In another aspect, the present invention provides a method for preparing the above-mentioned ACC-Gd-polymer multifunctional nanomaterial, which method includes adding suitable polymers or biological macromolecules to the ACC-Gd prepared according to the aforementioned method molecule, thereby obtaining the ACC-Gd-polymer multifunctional nanomaterial.

In another aspect, the application of the above-mentioned ACC-Gd or ACC-Gd-polymer multifunctional nanomaterial as drug loading or MRI contrast agent is provided.

The present invention obtains a novel multifunctional nanomaterial by stabilizing amorphous calcium carbonate ACC with the element Gd, wherein since Gd is in the crystal lattice of amorphous carbonic acid, the toxicity of Gd is greatly reduced, and Gd as a magnetic element has a good contrast effect, so the multifunctional nanomaterials can be used as MRI contrast agents. In addition, in order to increase the water solubility of the material, some polymers such as PAA are introduced, and the obtained ACC-Gd-PAA, for example, is negatively charged due to ACC itself, and the introduction of PAA's strong negatively charged group makes the multifunctional nanomaterial It has a strong adsorption capacity for positively charged materials (such as doxorubicin (DOX)), so it has very broad application prospects in drug loading and other fields.

Description of drawings

Fig. 1 is according to the X-ray of the ACC-Gd nano material ([Gd ³⁺ ]/[Ca ²⁺ ] molar ratio is 1/3, 1/4 and 1/5) obtained in Examples 1-3 of the present invention Diffraction analysis diagram.

FIG. 2 is an X-ray diffraction analysis diagram of the ACC-Gd nanomaterials obtained in Examples 2-3 after standing in the air for one week.

FIG. 3 is a scanning electron micrograph of ACC-Gd _1/5 obtained in Example 3. FIG.

FIG. 4 is an infrared spectrogram of ACC-Gd _1/5 -PAA obtained in Example 7. FIG.

Fig. 5 is an X-ray diffraction analysis diagram of ACC-Gd _1/5 -PAA obtained in Example 7 placed in deionized water for 4 months.

Fig. 6 is a photo of ACC-Gd _1/5 -PAA loaded with doxorubicin (DOX) obtained in Example 7 (mass ratio ACC/DOX=1/2 in the figure).

Fig. 7 is the NMR image of ACC-Gd _1/3 -PAA, ACC-Gd _1/4 -PAA, ACC-Gd _1/5 -PAA obtained in Example 7 as a T1 contrast agent, (wherein from above The concentration of the ACC-Gd-PAA nanometer material obtained by the present invention increases gradually).

Detailed ways

The inventors of the present invention have unexpectedly discovered that amorphous calcium carbonate (ACC) can be stabilized by introducing the element gadolinium (Gd) into it, thereby obtaining a novel multifunctional nanomaterial. Specifically, by doping the element gadolinium (Gd) into the amorphous calcium carbonate (ACC), the element Gd is in the crystal lattice of the amorphous ACC to stabilize the ACC and prevent the crystallization of the ACC, thereby simultaneously realizing the The magnetic elements are combined with green amorphous calcium carbonate to obtain a new ACC-Gd multifunctional nanomaterial. Further, by introducing suitable polymers or biopolymers into the ACC-Gd multifunctional materials to increase the water solubility of the multifunctional nanomaterials, and then obtain ACC-Gd-polymer multifunctional nanomaterials, such multifunctional Nanoparticles have a wide range of applications in biomedicine.

The multifunctional nanomaterials obtained by the present invention not only have many beneficial properties of calcium carbonate, a traditional mineralization material, but also because of the magnetic properties of Gd, and because Gd is located in the crystal lattice of ACC and surrounded by ACC, it greatly reduces the amount of elemental Gd itself is toxic, so the obtained nanomaterials can be used as MRI contrast agents. In addition, in the present invention, ACC-Gd-polymer multifunctional nanomaterials can be obtained by adding suitable polymers or biopolymers to the above-mentioned ACC-Gd nanomaterials. For example, ACC-Gd-PAA multifunctional nanomaterials can be obtained by the present invention, because ACC itself shows negative charge, and the introduction of PAA strong electronegative groups makes the obtained multifunctional nanomaterials positively charged materials such as ACC DOX has a strong adsorption capacity, so it also has very broad application prospects in drug loading and other fields.

In the preparation method of the ACC-Gd nano material of the present invention, the ACC is stabilized by doping the element Gd into the ACC, thereby obtaining a stabilized ACC, that is, the ACC-Gd nano material. In a preferred embodiment, first calcium (Ca) salt solution and gadolinium (Gd) salt solution are mixed, then carbonate solution is added, reacted under vigorous stirring, after filtering and drying, the ACC-Gd multifunctional nano Material. Preferably, equal volumes and equal concentrations of the Ca salt solution and the carbonate solution can be used.

In a preferred embodiment, the concentrations of the Ca salt solution and the carbonate solution used are both in the range of 0.1M-0.5M. Preferably, the Ca salt solution is a CaCl ₂ solution, but other Ca salt solutions such as Ca(NO ₃ ) ₂ solutions can also be used; the Gd salt solution is a GdCl ₃ solution, but other Gd salt solutions such as Gd (NO ₃ ) ₃ solution; the carbonate solution is Na ₂ CO ₃ solution, but other carbonate solutions such as K ₂ CO ₃ solution can also be used. The selection of these saline solutions is known to those skilled in the art.

In a preferred embodiment, the Ca salt solution and the Gd salt solution have a molar ratio of [Ca ²⁺ ]/[Gd ³⁺ ]=1-10 (or [Gd ³⁺ ]/[Ca ²⁺ ] =1/10-1) amount used.

The method for preparing ACC-Gd-polymer multifunctional nanomaterials of the present invention includes adding suitable polymers or biomacromolecules to the above-mentioned ACC-Gd nanomaterials to obtain the ACC-Gd-polymer multifunctional nanomaterials. In a preferred embodiment, the polymer or biomacromolecule is one or more selected from PAA, PSS and water-soluble amino acids.

The ACC-Gd or ACC-Gd-polymer multifunctional nanometer material obtained in the present invention can be used as drug loading or MRI contrast agent.

In a specific embodiment, elemental Gd is first incorporated into amorphous calcium carbonate (ACC), for example by preparing 25 ml of 0.1M CaCl ₂ solution and 5 ml of 0.1M GdCl ₃ solution ([Ca ²⁺ ]/[Gd ^{3 +} ] molar ratio between 1-10), after blending, add 25ml 0.1MNa ₂ CO ₃ solution, stir vigorously to obtain a white precipitate, and quickly wash the precipitate with ethanol (for example, with 4000r/min Centrifuge for 3 min) three times to obtain ACC-Gd solid precipitation, and dry in a vacuum oven at room temperature to obtain ACC-Gd solid powder.

In another specific embodiment, in order to increase the water solubility of ACC-Gd nanomaterials, some polymers are introduced, such as preparing 25ml of 0.1M CaCl ₂ solution and 5ml of 0.1M GdCl ₃ solution, such as in molar ratio [Ca ²⁺ ]/ [Polymer]=4/1 Add a polymer such as PAA or PSS, blend it, then add 25ml 0.1M _Na2CO3 solution, stir _vigorously to obtain a white precipitate, quickly wash the precipitate with ethanol (4000r /min, 3min) three times to obtain ACC-Gd-polymer solid precipitation, and dry in a vacuum oven at room temperature to obtain ACC-Gd-polymer solid powder.

In the present invention, Gd can stabilize the calcium carbonate formed in the reaction in an amorphous state, and maintain the particle size of calcium carbonate at the nanometer level, although the element Gd itself has certain toxicity, but due to the incorporation of Gd into the amorphous carbonic acid In calcium, where Gd is in the lattice of ACC, its toxic side effects can be greatly reduced, thereby increasing its biocompatibility, and the multifunctional nanomaterials obtained in this way are more suitable for biomedical applications such as drug loading or MRI imaging agent.

The preparation method of ACC-Gd-PAA of the present invention will be specifically described below in conjunction with the examples.

Example 1

Prepare ACC-Gd _1/3 (the subscript 1/3 here means that the molar ratio of [Gd ³⁺ ]/[Ca ²⁺ ] is 1/3) nanomaterials: mix 25ml 0.1M CaCl ₂ solution with 5ml 0.167M GdCl ₃ Mix the solution in a 100ml Erlenmeyer flask, then add 25ml 0.1M Na ₂ CO ₃ solution, stir vigorously to obtain a white precipitate, quickly wash the precipitate with ethanol (4000r/min, 3min) three times to obtain ACC-Gd _{1 /3} solid precipitated, and dried in a vacuum oven at room temperature for 24 hours to obtain ACC-Gd _1/3 solid powder. As shown in Figure 1, the X-ray diffraction analysis diagram shows that the calcium carbonate in the obtained ACC-Gd _1/3 powder is an amorphous phase, namely ACC.

Example 2

Preparation of ACC-Gd _1/4 (subscript 1/4 here means that the molar ratio of [Gd ³⁺ ]/[Ca ²⁺ ] is 1/4) nanomaterials: similar to Example 1, 25ml 0.1M CaCl ₂ The solution was mixed with 5ml of 0.125M GdCl ₃ solution, and then 25ml of 0.1M Na ₂ CO ₃ solution was added. After stirring vigorously, the precipitate was centrifuged and washed three times with ethanol, and dried to obtain ACC-Gd _1/4 solid powder. As shown in Figure 1, the X-ray diffraction analysis chart shows that the calcium carbonate in the obtained ACC-Gd _1/4 powder is an amorphous phase, namely ACC.

Example 3

Preparation of ACC-Gd _1/5 (subscript 1/5 here means that the molar ratio of [Gd ³⁺ ]/[Ca ²⁺ ] is 1/5) nanomaterials: similar to Example 1, 25ml 0.1M CaCl ₂ The solution was mixed with 5ml of 0.1M GdCl ₃ solution, and then 25ml of 0.1M Na ₂ CO ₃ solution was added. After stirring vigorously, the precipitate was centrifuged and washed three times with ethanol, and dried to obtain ACC-Gd _1/5 solid powder. As shown in Figure 1, the X-ray diffraction analysis chart shows that the calcium carbonate in the obtained ACC-Gd _1/5 powder is an amorphous phase, namely ACC.

Example 4

Preparation of ACC-Gd _1/10 (subscript 1/10 here means that the molar ratio of [Gd ³⁺ ]/[Ca ²⁺ ] is 1/10) nanomaterials: similar to Example 1, 25ml 0.1M CaCl ₂ The solution was mixed with 5ml of 0.05M GdCl ₃ solution, and then 25ml of 0.1M Na ₂ CO ₃ solution was added. After stirring vigorously, the precipitate was centrifuged and washed three times with ethanol, and dried to obtain ACC-Gd _1/10 solid powder. The analysis chart (not shown) by X-ray diffraction shows that the calcium carbonate in the obtained ACC-Gd _1/10 powder is an amorphous phase, namely ACC.

Example 5

Preparation of ACC-Gd _1/5 nanomaterials: the process is the same as in Example 3, except that 25ml of 0.3M CaCl ₂ solution, 5ml of 0.3M GdCl ₃ solution and 25ml of 0.3M Na ₂ CO ₃ solution are used. The analysis chart (not shown) by X-ray diffraction shows that the calcium carbonate in the obtained ACC-Gd _1/5 powder is an amorphous phase, namely ACC.

Example 6

Preparation of ACC-Gd _1/4 nanomaterials: the process is the same as in Example 2, except that 25ml of 0.5MCaCl ₂ solution, 5ml of 0.625M GdCl ₃ solution and 25ml of 0.5M Na ₂ CO ₃ solution are used. The analysis chart (not shown) by X-ray diffraction shows that the calcium carbonate in the obtained ACC-Gd _1/4 powder is an amorphous phase, that is, ACC.

Example 7

Preparation of ACC-Gd _1/5 -PAA nanomaterials: similar to Example 3, first 25ml 0.1MCaCl ₂ solution and 5ml 0.1M GdCl ₃ solution were mixed, and then the molar ratio [Ca ²⁺ ]/[PAA]=4/ Add PAA (M _w = 1800) in an amount of 1, and after fully blending, add 25ml of 0.1M Na ₂ CO ₃ solution, stir vigorously, and quickly wash the precipitate with ethanol for three times, and dry to obtain ACC-Gd _1/5 - PAA powder. Similarly, ACC-Gd _1/3 -PAA and ACC-Gd _1/4 -PAA nanomaterials can be prepared. Show that the calcium carbonate in the obtained ACC-Gd _1/5 -PAA, ACC-Gd _1/3 -PAA and ACC-Gd _1/4 -PAA powders is an amorphous phase by X-ray diffraction analysis figure (not shown) , namely ACC.

The nanomaterials obtained in the embodiments of the present invention will be further described below in conjunction with the accompanying drawings.

Fig. 1 is the X-ray diffraction of the ACC-Gd nanomaterials ([Gd ³⁺ ]/[Ca ²⁺ ] molar ratios are 1/3, 1/4 and 1/5 respectively) obtained in Examples 1 to 3 of the present invention Analysis chart. As shown in Figure 1, the calcium carbonate doped with Gd is an amorphous phase, that is, ACC, and it also shows that the incorporation of Gd can stabilize nano-ACC and obtain new multifunctional nanomaterials.

Fig. 2 is an X-ray diffraction analysis diagram of ACC-Gd nanomaterials obtained in Examples 2 and 3 of the present invention after standing in air for one week. _As ^shown in Figure 2, from the stability after one week of standing, the ACC-Gd ^1/5 nanometer The calcium carbonate crystallization peak that material appears is stronger than the calcium carbonate crystallization peak of the ACC-Gd _1/4 that obtains in embodiment 2 (the molar ratio of [Gd ³⁺ ]/[Ca ²⁺ ] is 1/4, and this shows that with With the increase of Gd incorporation, the stabilizing effect of ACC is enhanced. In addition, from other perspectives such as economic perspective, the amount of Gd doped should not be too large, that is, the molar ratio of [Gd ³⁺ ]/[Ca ²⁺ ] is preferably below 1.

Fig. 3 is a scanning electron microscope image of the ACC-Gd _1/5 nanometer material obtained in Example 3 of the present invention. It can be seen from Fig. 3 that the obtained ACC-Gd _1/5 powders are small spherical particles with a particle size below 100nm. Such nanoscale materials are very suitable for biomedical applications.

Fig. 4 is an infrared spectrogram of the ACC-Gd _1/5 -PAA nanomaterial obtained in Example 7 of the present invention. As shown in Figure 4, the smooth peak at 865cm ^-1 and the separated double peaks at 1419cm ^-1 and 1455cm ^-1 are typical infrared spectrum peaks of ACC, which shows that after the introduction of polymer PAA, the obtained product is still for ACC.

Fig. 5 is an X-ray diffraction analysis diagram of the ACC-Gd _1/5 -PAA nanomaterial obtained in Example 7 of the present invention placed in deionized water for 4 months. As can be seen from Figure 5, the X-ray diffraction analysis figure of this nanomaterial is similar to the result in Figure 1, and basically no crystallization peak occurs, indicating that the calcium carbonate at this time is still an amorphous phase, confirming that the obtained ACC-Gd _1/5 -PAA nanomaterials have good stability in aqueous solution.

Fig. 6 is the photo of the ACC-Gd _1/5 -PAA nanomaterial obtained in Example 7 of the present invention loaded with doxorubicin (DOX), wherein the ACC-Gd _1/5 -PAA obtained in the present invention is a white precipitate, and DOX is a red water-soluble material. As can be seen from Figure 6, the red precipitate in the photo shows that quite a lot of red DOX is adsorbed on the ACC-Gd _1/5 -PAA nanomaterial, which fully illustrates the ACC-Gd _1/5 -PAA nanomaterial obtained by the present invention It has a strong adsorption capacity for DOX. Further, in order to calculate the utilization rate of DOX by the nanomaterial, the ACC-Gd _1/5 -PAA nanomaterial adsorbed by DOX was centrifuged (8000r/min, 5min), and the DOX in the obtained supernatant was unadsorbed DOX, because DOX has fluorescence, so measure the fluorescence value of the supernatant. Different concentrations of DOX were then prepared, and the fluorescence values were measured by a fluorescence spectrophotometer to obtain a standard curve. According to the fluorescence value of the above supernatant, the corresponding concentration of DOX can be obtained in the standard curve, so that the amount of DOX adsorbed by the nanometer material of the present invention can be calculated. As a result, it is calculated after testing that the utilization rate of DOX of the nanomaterial of the present invention is 97.20% (mass ratio ACC/DOX=1/2 in the figure).

Fig. 7 is the NMR image of ACC-Gd _1/3 -PAA, ACC-Gd _1/4 -PAA and ACC-Gd _1/5 -PAA nanomaterials obtained in Example 7 of the present invention as a T1 contrast agent, wherein The concentration (conc.) of nanomaterials obtained by the present invention increases gradually from top to bottom, repeat time TR=4000ms, echo time TE=500ms, DIW means deionized water. It can be clearly seen from Fig. 7 that, from top to bottom, as the concentration of the nanomaterials of the present invention increases, the contrast intensity becomes brighter, that is, the contrast effect of the above-mentioned nanomaterials changes with the concentration, and the higher the concentration Larger, stronger contrast intensity. Moreover, in Fig. 7, the Gd concentration in the above nanomaterials gradually decreases from left to right, that is, ACC-Gd _1/3 -PAA, ACC-Gd _1/4 -PAA and ACC-Gd _1/5 -PAA , and for different nanomaterials with the same concentration, it can be seen from Figure 7 that the contrast intensity of the nanomaterial samples in the same horizontal row is getting darker from left to right, that is to say, as the Gd concentration gradually decreases, the contrast intensity becomes darker. getting weaker.

Therefore, as can be seen from the above, Gd can stabilize ACC, and the ACC-Gd and ACC-Gd-polymers such as ACC-Gd-PAA obtained by the present invention are widely used in biomedical fields such as drug loading and MRI contrast agents. Foreground, e.g. as drug loading or contrast media.

The present invention has been described in detail above, but the present invention is not limited to the specific embodiments described herein. Those skilled in the art understand that other changes and modifications can be made without departing from the scope of the present invention. The scope of the invention is defined by the appended claims.

Claims (10)

1. An ACC-Gd multifunctional nanomaterial obtained by stabilizing amorphous calcium carbonate (ACC) with element gadolinium (Gd), wherein the ACC-Gd multifunctional nanomaterial is obtained as follows: the element gadolinium ( Gd) is doped into the amorphous calcium carbonate (ACC), the element Gd being in the crystal lattice of the amorphous calcium carbonate (ACC) to stabilize the ACC. 2. a kind of ACC-Gd-polymer multifunctional nanomaterial, described ACC-Gd-polymer multifunctional nanomaterial is by introducing suitable polymer or biological compound in the ACC-Gd multifunctional nanomaterial according to claim 1 obtained from macromolecules. 3. ACC-Gd-polymer multifunctional nanomaterial according to claim 2, characterized in that, said polymer or biomacromolecule is one or more selected from PAA, PSS and water-soluble amino acids. 4. A method for preparing the ACC-Gd multifunctional nanomaterial according to claim 1, said method comprising introducing Gd into the ACC so that the ACC is stable, thereby obtaining said ACC-Gd multifunctional nanomaterial, Wherein the element gadolinium (Gd) is doped into the amorphous calcium carbonate (ACC), and the element Gd is in the crystal lattice of the amorphous calcium carbonate (ACC) to stabilize the ACC. 5. The method according to claim 4, characterized in that first calcium (Ca) salt solution and Gd salt solution are mixed, then carbonate solution is added, reacted under vigorous stirring, filtered and dried to obtain the ACC -Gd multifunctional nanomaterials. 6. The method according to claim 5, characterized in that equal volumes and equal concentrations of the Ca salt solution and the carbonate solution are used. 7. The method according to claim 6, characterized in that the concentration of the Ca salt solution and the carbonate solution used is 0.1M-0.5M. 8. The method according to claim 5, wherein the Ca salt solution is a CaCl ₂ solution, the Gd salt solution is a GdCl ₃ solution, and the carbonate solution is a Na ₂ CO ₃ solution. 9 . The method according to claim 5 , wherein the Ca salt solution and the Gd salt solution are used in a molar ratio of [Ca ²⁺ ]/[Gd ³⁺ ]=1-10. 10. A method for preparing the ACC-Gd-polymer multifunctional nanomaterial described in claim 2 or 3, said method comprising the ACC-Gd multifunctional nanomaterial described in claim 1 or claim 4 Add suitable polymers or biomacromolecules to the ACC-Gd multifunctional nanomaterial prepared by the method described in any one of -9, so as to obtain the ACC-Gd-polymer multifunctional nanomaterial.

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