A bimodal functional imaging nanomaterial and a preparation method and application thereof

Abstract

The application belongs to the technical field of material preparation, and relates to a bimodal functional imaging nanomaterial and a preparation method and application thereof. 1‑x Fe x Se2, wherein 0 < x < 1. The preparation method of the bimodal functional imaging nanomaterial comprises the following steps: stirring ferrous sulfate and cysteine in a solvent until uniform, then fully stirring bismuth salt, then adding sodium selenite to perform a heating reaction to obtain a bismuth iron selenium nanocomposite. The bismuth iron selenium nanocomposite provided by the application is uniform in size, regular in morphology, has good water phase dispersibility, and has the performance of simultaneously enhancing MRI imaging and CT imaging.

Description

Technical Field

[0001] This invention belongs to the field of materials preparation technology, and relates to a nanomaterial for dual-modal functional imaging, its preparation method, and its application. Background Technology

[0002] Nanomaterials, due to their unique properties—good biocompatibility, small size, and high surface area—have prominent applications in the biomedical field. Magnetic resonance imaging (MRI), as a non-invasive medical imaging technique, boasts unique advantages of safety and high contrast, and is widely used in clinical disease diagnosis. Computed tomography (CT) utilizes the different absorption of X-rays by different tissues to produce different imaging effects, and is generally used for imaging dense tissues. Traditional MRI and CT scans do not provide good imaging contrast, therefore, a certain amount of contrast agent is needed to enhance imaging contrast, which is beneficial for better and more accurate disease diagnosis. Clinically, MRI contrast agents are usually gadolinium chelates, including gadopentetate dimeglumine, while CT contrast agents generally use iodine preparations, such as iodofol. Iron selenide has a suitable bandgap and is widely used and researched in the fields of optics and magnetism. Nanoscale iron selenide possesses the advantages of its nanoscale size and also has certain photothermal conversion capabilities, showing great application potential in magnetic resonance imaging, biosensing, and cancer treatment. Bismuth has a high atomic number (z=83) and a high X-ray attenuation coefficient, and has been extensively studied in CT imaging. Currently, the most studied CT imaging materials are mainly bismuth-based nanomaterials.

[0003] Traditional MRI contrast agents and CT contrast agents are two different substances. Currently, there is no drug in clinical practice that can simultaneously achieve the enhancement effect of CT and MRI imaging. However, combining CT and MRI imaging techniques can effectively improve the detection rate and accuracy of tumors or other diseases, which has important clinical significance. Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of existing technologies by providing a nanomaterial for dual-modal functional imaging, its preparation method, and its application.

[0005] One object of the present invention is to provide a nanomaterial for dual-modal functional imaging, wherein the dual-modal functional imaging nanomaterial is a bismuth-iron-selenium nanocomposite with the molecular formula Bi. 1-x Fe x Se2, where 0 < x < 1.

[0006] Preferably, the particle size of the bismuth-iron-selenium nanocomposite is 5–20 nm.

[0007] Another object of the present invention is to provide a method for preparing the above-mentioned dual-modal functional imaging nanomaterials, comprising the following steps:

[0008] Ferrous sulfate and cysteine ​​were added to a solvent and stirred until homogeneous. Then, bismuth salt was added and stirred thoroughly. Sodium selenite was then added and heated to react, yielding a bismuth-iron-selenium nanocomposite.

[0009] Bismuth-iron-selenium nanocomposites were prepared by heating ferrous sulfate, bismuth salt, and sodium selenite in a solvent under the action of cysteine. The bismuth-iron-selenium nanocomposites have uniform size, regular morphology, and good aqueous dispersibility.

[0010] The bismuth iron selenium nanocomposite prepared by the above method has the ability to simultaneously enhance MRI and CT imaging.

[0011] Ferrous sulfate can be either anhydrous FeSO4 or FeSO4 hydrate.

[0012] Preferably, the solvent is one or more of N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), and N-methyl-2-pyrrolidone (NMP).

[0013] Preferably, the bismuth salt is bismuth trichloride and / or bismuth nitrate. Bismuth trichloride and / or bismuth nitrate can be anhydrous or hydrated.

[0014] Preferably, the molar ratio of ferrous sulfate to cysteine ​​is 1:(1-5).

[0015] Preferably, the ratio of the total molar amount of ferrous sulfate and bismuth salt to the molar amount of sodium selenite is 0.9:2.0 to 1.1:2.5.

[0016] Preferably, the molar ratio of ferrous sulfate to bismuth salt is greater than 1.

[0017] Preferably, in the above-mentioned method for preparing nanomaterials for dual-modal functional imaging, the heating reaction is carried out at 120–180°C for 15–40 h.

[0018] Another object of the present invention is to provide the application of the above-mentioned bimodal functional imaging nanomaterials for MRI imaging and / or CT imaging.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] 1. This invention integrates the powerful advantages of iron selenide and bismuth elements, and synthesizes bismuth iron selenide nanomaterials by solvothermal method through ion doping, thereby obtaining dual-modal imaging functions of CT and MRI, which can be used for tumor diagnosis and real-time imaging, as well as for cancer treatment through photothermal therapy.

[0021] 2. Currently, there is no drug in clinical practice that can simultaneously achieve the enhancement effects of CT and MR imaging. The bismuth iron selenium nanocomposite provided by this invention integrates the dual-modal imaging performance of CT and MRI, providing a good and feasible approach to solving the problem of combining MR and CT enhancement effects in clinical practice. Attached Figure Description

[0022] Figure 1 a is Bi prepared in Example 1 0.025 Fe 0.975 Transmission electron microscopy (TEM) image of Se2. Figure 1 b is the Bi prepared in Example 2. 0.05 Fe 0.95 Transmission electron microscopy (TEM) image of Se2. Figure 1 c represents the Bi prepared in Example 3. 0.1 Fe 0.9 Transmission electron microscopy (TEM) image of Se2. Figure 1 d represents Bi prepared in Example 4. 0.2 Fe 0.8 Se 22 Transmission electron microscope (TEM) image, Figure 1 e is Bi prepared in Example 5 0.3 Fe 0.7 Transmission electron microscopy (TEM) image of Se2;

[0023] Figure 2 Bi prepared in Example 1 0.025 Fe 0.975 MRI images of Se2;

[0024] Figure 3 Bi prepared in Example 2 0.05 Fe 0.95 MRI images of Se2;

[0025] Figure 4 Bi prepared in Example 3 0.1 Fe 0.9 MRI images of Se2;

[0026] Figure 5 Bi prepared in Example 1 0.025 Fe 0.975 Se2 and Bi prepared in Example 2 0.05 Fe 0.95 CT image of Se2. Detailed Implementation

[0027] The technical solution of the present invention will be further described and illustrated below with reference to specific embodiments and accompanying drawings. It should be understood that the specific embodiments described herein are only for the purpose of helping to understand the present invention and are not intended to limit the specific scope of the present invention. Furthermore, the accompanying drawings used herein are merely for better illustrating the content disclosed in the present invention and do not limit the scope of protection. Unless otherwise specified, the raw materials used in the embodiments of the present invention are all commonly used in the art, and the methods used in the embodiments are all conventional methods in the art.

[0028] Example 1

[0029] The molecular formula of the bismuth-iron-selenium nanocomposite in this embodiment is Bi. 0.025 Fe 0.975 Se2 is prepared by the following method:

[0030] Weigh 0.975 mmol FeSO4·7H2O and 2 mmol cysteine ​​and add them to 35 ml DMF. Stir thoroughly until homogeneous. Then add 0.025 mmol bismuth nitrate pentahydrate and stir thoroughly until dissolved. Add 2 mmol sodium selenite (Na2SeO3) and sonicate for five minutes until fully dissolved. Finally, transfer to a 50 ml reactor and react at 140 °C for 20 h. After the reaction is complete, cool to room temperature and wash twice with anhydrous ethanol and deionized water, respectively. Finally, disperse in 20 ml deionized water and store at 4 °C for later use.

[0031] Figure 1 a is Bi prepared in Example 1 0.025 Fe 0.975 The transmission electron microscope (TEM) image of Se2 shows that Bi 0.025 Fe 0.975 Se2 particles are uniform in size and regular in morphology, with an average particle size of 5–20 nm.

[0032] Figure 2 Bi prepared in Example 1 at different concentrations 0.025 Fe 0.975 T2-weighted MRI images of Se2 under a magnetic field of 0.45T. Figure 2 The brightest element is deionized water, and the others are bismuth-iron-selenium nanocomposite materials of different concentrations, from top to bottom: 0.8, 0.4, 0.2, and 0.1 mmol / L. As can be seen from the figure, Bi... 0.025 Fe 0.975 Se2 has certain T2-weighted MRI imaging performance.

[0033] Figure 5 Figure a in the diagram is Bi 0.025 Fe 0.975The CT images of Se show concentration distributions from left to right of 0, 0.018, 0.375, 0.075, and 0.15 mg / ml, from which Bi can be observed. 0.025 Fe 0.975 Se2 has certain CT performance.

[0034] Example 2

[0035] The molecular formula of the bismuth-iron-selenium nanocomposite in this embodiment is Bi. 0.05 Fe 0.95 Se2 is prepared by the following method:

[0036] Weigh 0.95 mmol FeSO4·7H2O and 2 mmol cysteine ​​and add them to 30 ml DMF. Stir thoroughly until homogeneous. Then add 0.05 mmol bismuth nitrate pentahydrate and stir thoroughly until dissolved. Add 2 mmol sodium selenite (Na2SeO3) and sonicate for five minutes until fully dissolved. Finally, transfer to a 50 ml reaction vessel and react at 160 °C for 18 h. After the reaction is complete, cool to room temperature and wash twice with anhydrous ethanol and deionized water, respectively. Finally, disperse in 20 ml deionized water and store at 4 °C for later use.

[0037] Figure 1 b is the Bi prepared in Example 2. 0.05 Fe 0.95 The transmission electron microscope (TEM) image of Se2 shows that Bi 0.05 Fe 0.95 Se2 particles are uniform in size and regular in morphology, with an average particle size of 5–10 nm.

[0038] Figure 3 Bi prepared for different concentrations in Example 2 0.05 Fe 0.95 T2-weighted MRI images of Se2 under a magnetic field of 0.45T. Figure 3 The brightest signal in the middle is deionized water, and the others are bismuth-iron-selenium nanocomposite materials of different concentrations, from top to bottom: 0.8, 0.4, 0.2, and 0.1 mmol / L. As can be seen from the figure, Bi... 0.05 Fe 0.95 Se2 has certain T2-weighted MRI imaging performance.

[0039] Figure 5 Figure b in the diagram represents Bi. 0.05 Fe 0.95 The CT images of Se show concentration distributions from left to right of 0, 0.018, 0.375, 0.075, and 0.15 mg / ml, from which Bi can be observed. 0.025 Fe 0.975Se2 has good CT performance.

[0040] Example 3

[0041] The molecular formula of the bismuth-iron-selenium nanocomposite in this embodiment is Bi. 0.1 Fe 0.9 Se2 is prepared by the following method:

[0042] Weigh 0.9 mmol FeSO4·7H2O and 2 mmol cysteine ​​and add them to 50 ml DMF. Stir thoroughly until homogeneous. Then add 0.1 mmol bismuth nitrate pentahydrate and stir thoroughly until dissolved. Add 2 mmol sodium selenite (Na2SeO3) and sonicate for five minutes until fully dissolved. Finally, transfer to an 80 ml reactor and react at 150 °C for 22 h. After the reaction is complete, cool to room temperature and wash twice with anhydrous ethanol and deionized water, respectively. Finally, disperse in 20 ml deionized water and store at 4 °C for later use.

[0043] Figure 1 c represents the Bi prepared in Example 3. 0.1 Fe 0.9 The transmission electron microscope (TEM) image of Se2 shows that Bi 0.1 Fe 0.9 Se2 particles are uniform in size and regular in morphology, with an average particle size of 5–10 nm.

[0044] Figure 4 Bi prepared for different concentrations in Example 3 0.1 Fe 0.9 T2-weighted MRI imaging of Se2 under a magnetic field of 0.45T. Figure 4 The brightest signal in the middle is deionized water, and the others are bismuth-iron-selenium nanocomposite materials of different concentrations, from top to bottom: 0.8, 0.4, 0.2, and 0.1 mmol / L. As can be seen from the figure, Bi... 0.1 Fe 0.9 Se2 has certain T2-weighted MRI imaging performance.

[0045] Example 4

[0046] The molecular formula of the bismuth-iron-selenium nanocomposite in this embodiment is Bi. 0.2 Fe 0.8 Se2 is prepared by the following method:

[0047] Weigh 0.8 mmol FeSO4·7H2O and 2 mmol cysteine ​​and add them to 35 ml DMF. Stir thoroughly until homogeneous. Then add 0.2 mmol bismuth nitrate pentahydrate and stir thoroughly until dissolved. Add 2 mmol sodium selenite (Na2SeO3) and sonicate for five minutes until fully dissolved. Finally, transfer to a 50 ml reaction vessel and react at 140 °C for 20 h. After the reaction is complete, cool to room temperature and wash twice with anhydrous ethanol and deionized water, respectively. Finally, disperse in 20 ml deionized water and store at 4 °C for later use.

[0048] Figure 1 d represents Bi prepared in Example 1. 0.2 Fe 0.8 Se 22 The transmission electron microscope (TEM) image shows that Bi 0.2 Fe 0.8 Se2 particles are uniform in size and regular in morphology, with an average particle size of 5–20 nm.

[0049] Example 5

[0050] The molecular formula of the bismuth-iron-selenium nanocomposite in this embodiment is Bi. 0.3 Fe 0.7 Se2 is prepared by the following method:

[0051] Weigh 0.7 mmol FeSO4·7H2O and 2 mmol cysteine ​​and add them to 35 ml DMF. Stir thoroughly until homogeneous. Then add 0.025 mmol bismuth nitrate pentahydrate and stir thoroughly until dissolved. Add 2 mmol sodium selenite (Na2SeO3) and sonicate for five minutes until fully dissolved. Finally, transfer to a 50 ml reactor and react at 140 °C for 20 h. After the reaction is complete, cool to room temperature and wash twice with anhydrous ethanol and deionized water, respectively. Finally, disperse in 20 ml deionized water and store at 4 °C for later use.

[0052] Figure 1 e is Bi prepared in Example 1 0.3 Fe 0.7 The transmission electron microscope (TEM) image of Se2 shows that Bi 0.3 Fe 0.7 Se2 particles are uniform in size and regular in morphology, with an average particle size of 10–20 nm.

[0053] All aspects, embodiments, and features of this invention should be considered illustrative in all respects and not limiting of the invention; the scope of the invention is defined only by the claims. Other embodiments, modifications, and uses will become apparent to those skilled in the art without departing from the spirit and scope of the invention as claimed.

[0054] In the preparation method of this invention, the order of the steps is not limited to the listed order. For those skilled in the art, variations in the order of the steps without creative effort are also within the scope of protection of this invention. Furthermore, two or more steps or actions can be performed simultaneously.

[0055] Finally, it should be noted that the specific embodiments described herein are merely illustrative examples of the invention and are not intended to limit the implementation of the invention. Those skilled in the art can make various modifications or additions to the described specific embodiments or use similar methods to replace them; it is neither necessary nor possible to exemplify all embodiments here. However, these obvious variations or modifications derived from the essential spirit of the invention still fall within the scope of protection of the invention, and interpreting them as any additional limitation would contradict the spirit of the invention.

Claims

1. A bimodal functional imaging nanomaterial, characterized in that, The bimodal functional imaging nanomaterial is a bismuth iron selenium nanocomposite, and the molecular formula is Bi 1-x Fe x Se2, wherein 0 < x < 1; the particle size of the bismuth iron selenium nanocomposite is 5-20 nm; The preparation method of the bimodal functional imaging nanomaterial comprises the following steps: adding ferrous sulfate and cysteine into a solvent and stirring uniformly, then adding bismuth salt and stirring fully, and then adding sodium selenite and reacting at 120-180 DEG C for 15-40 h to obtain a bismuth-iron-selenium nanocomposite. The molar ratio of ferrous sulfate to cysteine is 1:(1-5). The ratio of the total molar amount of ferrous sulfate and bismuth salt to the molar amount of sodium selenite is 1:2-1:2.

5.

2. The bimodal functional imaging nanomaterial of claim 1, wherein, The solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidone.

3. The bimodal functional imaging nanomaterial of claim 1, wherein, The bismuth salt is bismuth trichloride and / or bismuth nitrate.

4. The method of claim 1, wherein the nanomaterial is a bimodal functional imaging nanomaterial. The preparation method comprises the following steps: adding ferrous sulfate and cysteine into a solvent and stirring uniformly, then adding bismuth salt and stirring fully, and then adding sodium selenite and reacting at 120-180 DEG C for 15-40 h to obtain a bismuth-iron-selenium nanocomposite.

5. The production method according to claim 4, characterized by, The solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidone.

6. The preparation method according to claim 4, characterized in that, The bismuth salt is bismuth trichloride and / or bismuth nitrate.

7. The use of a bimodal functionalized nanomaterial for imaging according to claim 1, wherein the bimodal functionalized nanomaterial is a bimodal functionalized nanomaterial according to claim 1. The bimodal functional imaging nanomaterial is used for preparing an MRI imaging and / or CT imaging contrast agent.

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