Gold nanoparticle enhancer for magnetic resonance elastography and preparation method and application thereof

Abstract

This invention discloses a gold nanoparticle enhancer for magnetic resonance elastography, its preparation method, and its application, belonging to the field of medical imaging technology. The preparation method includes dissolving trisodium citrate in deionized water to obtain solution A, then adding chloroauric acid solution to generate solution B. When the temperature of solution B drops to 90°C, an equal amount of chloroauric acid solution is added to form solution C and stirred. An equal amount of chloroauric acid solution is added again and stirred to form solution D. After the reaction is complete, ultrafiltration, centrifugation, and washing are performed to obtain the gold nanoparticle enhancer. This invention achieves the controllable synthesis of the gold nanoparticle enhancer. The preparation method is simple, easy to operate, and has good reproducibility. The obtained gold nanoparticle enhancer has uniform particle size, good dispersibility, and excellent stability, making it easy to scale up production. More importantly, the gold nanoparticle enhancer prepared by this invention has excellent low toxicity and good biocompatibility.

Description

Technical Field

[0001] This invention belongs to the field of medical imaging technology, specifically relating to gold nanoparticle enhancers for magnetic resonance elastography, their preparation methods, and applications. Background Technology

[0002] Magnetic resonance imaging (MRI), as the cornerstone of modern medical imaging technology, plays an irreplaceable role in the early diagnosis of diseases of the nervous, cardiovascular, and musculoskeletal systems due to its advantages of no ionizing radiation damage, high soft tissue resolution, and multi-parameter imaging. As an important extension of MRI, magnetic resonance elastography (MRE) introduces external mechanical vibrations and uses phase-contrast sequences to quantitatively measure tissue elastic parameters. This provides crucial biomechanical information for diseases such as liver fibrosis staging, differentiation of benign and malignant tumors, and assessment of brain lesions, effectively compensating for the shortcomings of traditional MRI in the quantitative assessment of tissue stiffness.

[0003] However, MRE technology still faces significant challenges in practical clinical applications. Particularly in tissues with low elasticity differences, the weak phase signal generated by mechanical wave propagation due to the low elastic contrast between tissues makes imaging highly susceptible to noise interference, limiting the detection rate of minute lesions and reducing diagnostic accuracy. This technical bottleneck highlights the urgent need for high-performance contrast agents to enhance the sensitivity and specificity of MRE signals and improve the quantitative diagnostic capability for early lesions.

[0004] Gold nanoparticles (AuNPs) exhibit broad application prospects in biomedical imaging due to their unique physicochemical properties. Their nanoscale size (1-100 nm), approaching the scale of biomacromolecules, endows them with excellent surface plasmon resonance (SPR) properties. By controlling the synthesis conditions, the particle size, morphology, and elastic modulus can be precisely designed, thereby optimizing their magnetic response characteristics. In cardiovascular disease models, gold nanoparticles have demonstrated good targeted delivery capabilities as drug carriers. For example, by surface functionalization with targeting molecules such as transferrin or folic acid, they can specifically bind to diseased tissues, reducing background signal interference. In elastography applications, the high atomic number of gold nanoparticles can improve the propagation efficiency of mechanical waves in tissues, while their tunable stiffness helps improve the signal-to-noise ratio of phase signals. Simultaneously, the surface of gold nanoparticles is easily modified with biomolecules such as peptides and aptamers, enabling targeted enrichment of specific tissues and thus enhancing the measurement accuracy of local elastic parameters.

[0005] Although gold nanoparticles have made some progress in MRI contrast agent research, their application in the field of MRE is still in the early stages of exploration, and the existing technology has the following obvious shortcomings: First, there is a lack of dedicated gold nanoparticle designs for MRE signal enhancement. Existing studies are mostly focused on tumor-targeted imaging or CT / MRI dual-modal imaging, without fully considering the special requirements of MRE technology for contrast agent elastic modulus, mechanical wave coupling efficiency, etc., resulting in limited enhancement effect of gold nanoparticles in MRE.

[0006] Second, the structure-activity relationship between the elastic imaging mechanism of gold nanoparticles and their nanostructure is still unclear. The size, surface modification and aggregation state of the particles affect key physical processes such as mechanical wave propagation and phase signal generation, which lacks systematic research and limits the ability to rationally design efficient MRE contrast agents.

[0007] Third, the biosafety assessment of gold nanoparticles in long-term elasticity monitoring is insufficient. Although gold nanoparticles are considered to have low in vivo toxicity, their biocompatibility and potential toxicity risks under repeated administration and long-term retention conditions have not been fully verified, which has become an important obstacle to clinical translation.

[0008] Fourth, existing synthesis methods struggle to balance particle uniformity, stability, and the demands of large-scale production. Gold nanoparticles prepared by the traditional citric acid reduction method exhibit a wide particle size distribution and lack effective means to control the elastic modulus, limiting their potential application in the precise diagnosis of elasticity-related diseases such as liver fibrosis.

[0009] To address the aforementioned issues, we propose a gold nanoparticle enhancer for magnetic resonance elastography, along with its preparation method and applications. Summary of the Invention

[0010] The purpose of this invention is to address the shortcomings of existing technologies by providing gold nanoparticle enhancers for magnetic resonance elastography, their preparation methods, and applications. This invention solves the problems of existing technologies, such as the lack of dedicated gold nanoparticle designs for MRE signal enhancement, the unclear structure-activity relationship between the elastography mechanism of gold nanoparticles and their nanostructures, insufficient biosafety assessment of gold nanoparticles in long-term elastography monitoring, and the difficulty of existing synthesis methods in simultaneously addressing particle uniformity, stability, and the requirements for large-scale production.

[0011] This invention is achieved by providing a method for preparing a gold nanoparticle enhancer for magnetic resonance elastography, the method comprising: S10, take trisodium citrate, dissolve trisodium citrate in deionized water to obtain solution A, boil and stir solution A, then add chloroauric acid solution to generate solution B; S20, when the temperature of solution B drops to 90℃, add the same amount of chloroauric acid solution as in step S10 to form solution C and stir; S30, add the same amount of chloroauric acid solution as in step S10 and stir to form solution D. After the reaction is complete, ultrafilter, centrifuge and wash to obtain gold nanoparticle reinforcing agent.

[0012] Preferably, in step S10, the ratio of the amount of trisodium citrate to deionized water is 2.2 mM: 150 mL; and the ratio of the volume of deionized water in solution A to the volume of deionized water in solution B is 150: 1.

[0013] Preferably, in solution B, the ratio of chloroauric acid solution to deionized water is 25 mM: 1 mL.

[0014] Preferably, in step S10, when boiling and stirring solution A, the stirring is a magnetic stirrer with a rotation speed of 800 rpm.

[0015] Preferably, in step S20, the ratio of the amount of chloroauric acid solution to deionized water added is 25 mM: 1 mL; the stirring is magnetic stirring at a speed of 800 rpm, and the stirring reaction time is 0.5 h.

[0016] Preferably, in step S30, the ratio of the amount of chloroauric acid solution to deionized water added is 25 mM: 1 mL, the stirring is magnetic stirring at a speed of 800 rpm, and the stirring reaction time is 0.5 h.

[0017] Preferably, in step S30, when obtaining the gold nanoparticle reinforcing agent by ultrafiltration centrifugation, the rotation speed of the ultrafiltration centrifugation is 3800 x g and the time is 10 min, and the washing is done by washing twice with deionized water.

[0018] On the other hand, the present invention also provides a gold nanoparticle enhancer for magnetic resonance elastography, which is prepared by the method described above.

[0019] Furthermore, the present invention also provides the application of the gold nanoparticle enhancer for magnetic resonance elastography in the preparation of magnetic resonance elastography sensitizing agents.

[0020] Compared with the prior art, the embodiments of this application have the following main advantages: In this invention, trisodium citrate was used as a reducing agent and stabilizer, and chloroauric acid solution was added in batches to achieve the controllable synthesis of gold nanoparticle reinforcing agents. This preparation method is simple, highly operable, and reproducible. The resulting gold nanoparticle reinforcing agents exhibit uniform particle size, good dispersibility, and excellent stability, making them easy to mass-produce. More importantly, the gold nanoparticle reinforcing agents prepared in this invention possess excellent low toxicity and good biocompatibility. Cell experiments and hemolysis experiments have both confirmed their good biocompatibility. Simultaneously, their tunable stiffness characteristics can effectively enhance the propagation efficiency of mechanical waves in tissues, improve the phase signal-to-noise ratio of magnetic resonance elastography (MRE), and significantly improve imaging results. Animal experiments show that, after tail vein injection, this gold nanoparticle reinforcing agent can significantly enhance the MRE effect on the liver of SD rats, effectively improving the quantitative diagnostic ability of MRE for early lesions, and has broad clinical application prospects in the early diagnosis of diseases such as liver fibrosis and tumors. Attached Figure Description

[0021] Figure 1 Transmission electron microscopy (TEM) images of gold nanoparticle enhancers for magnetic resonance elastography prepared according to embodiments of the present invention are shown.

[0022] Figure 2 The hydrated particle size diagram of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention is shown.

[0023] Figure 3 The absorbance curve of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention is shown.

[0024] Figure 4 The Fourier transform infrared spectrum of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention is shown.

[0025] Figure 5 The figure shows the experimental results of the cell biocompatibility of the gold nanoparticle enhancer prepared according to the embodiments of the present invention.

[0026] Figure 6 The graph shows the hemolysis rate test results of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention.

[0027] Figure 7 The image shows the magnetic resonance elastography effect of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention.

[0028] Figure 8 The figure shows the quantitative results of the elastic modulus of the gold nanoparticle reinforcing agent prepared according to the embodiments of the present invention during magnetic resonance elastography. Detailed Implementation

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs; the terminology used herein in the specification of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application; the terms "comprising" and "having," and any variations thereof, in the specification, claims, and foregoing drawings of this application are intended to cover non-exclusive inclusion. The terms "first," "second," etc., in the specification, claims, or foregoing drawings of this application are used to distinguish different objects, not to describe a particular order.

[0030] As introduced in the background section, current magnetic resonance elastography (MRE) suffers from several problems. In tissues with low elasticity differences, the imaging effect is easily affected by noise, leading to a decrease in diagnostic accuracy. Furthermore, existing technologies lack dedicated gold nanoparticle designs for MRE signal enhancement. The structure-activity relationship between the elastography mechanism of gold nanoparticles and their nanostructure is still unclear. The biosafety assessment of gold nanoparticles in long-term elasticity monitoring is insufficient, and existing synthesis methods struggle to balance particle uniformity, stability, and large-scale production requirements. To address these issues, we propose a gold nanoparticle enhancer for MRE, its preparation method, and its application. In short, the preparation of the gold nanoparticle enhancer involves first dissolving trisodium citrate in deionized water to obtain solution A. Solution A is boiled and stirred, then chloroauric acid solution is added to generate solution B. When the temperature of solution B drops to 90°C, an equal dose of chloroauric acid solution is added to form solution C and stirred. Another equal dose of chloroauric acid solution is added and stirred to form solution D. After the reaction is complete, the gold nanoparticle enhancer is obtained by ultrafiltration, centrifugation, and washing. In this invention, trisodium citrate was used as a reducing agent and stabilizer, and chloroauric acid solution was added in batches to achieve the controllable synthesis of gold nanoparticle enhancers. This preparation method is simple, highly operable, and reproducible. The resulting gold nanoparticle enhancers exhibit uniform particle size, good dispersibility, and excellent stability, making them easy to mass-produce. More importantly, the gold nanoparticle enhancers prepared by this invention possess excellent low toxicity and good biocompatibility. Cell experiments and hemolysis experiments have confirmed their good biosafety. Simultaneously, their tunable stiffness characteristics can effectively improve the propagation efficiency of mechanical waves in tissues, enhance the phase signal-to-noise ratio of magnetic resonance elastography (MRE), and significantly improve imaging results. Animal experiments show that, after tail vein injection, this gold nanoparticle enhancer can significantly enhance the MRE effect on the liver of SD rats, effectively improving the quantitative diagnostic ability of MRE for early lesions, and has broad clinical application prospects in the early diagnosis of diseases such as liver fibrosis and tumors.

[0031] To enable those skilled in the art to better understand the technical solution of this application, the technical solution of this application will be described in detail below with reference to specific embodiments.

[0032] It should be noted that the test materials used in the embodiments of the present invention are all conventional test materials in the art and can be purchased through commercial channels. Example 1

[0033] This invention provides a method for preparing gold nanoparticle enhancers for magnetic resonance elastography, the method specifically comprising: S10, take 98 mg of trisodium citrate and dissolve it in 150 ml of deionized water to obtain solution A, i.e., a 2.2 mM trisodium citrate solution. Boil and stir solution A (2.2 mM trisodium citrate solution), then add 1 mL of 25 mM chloroauric acid solution to generate solution B. In step S10, the ratio of added trisodium citrate to deionized water is 2.2 mM:150 mL; the volume ratio of deionized water in solution A to that in solution B is 150:1. In solution B, the ratio of added chloroauric acid solution to deionized water is 25 mM:1 mL. When boiling and stirring solution A, the stirring is magnetic stirring at a speed of 800 rpm.

[0034] S20, turn off the heater and allow the solution temperature to slowly drop to 90°C. When the temperature of solution B drops to 90°C, add the same amount of chloroauric acid solution as in step S10 to form solution C and stir. In step S20, the ratio of the amount of chloroauric acid solution to deionized water added is 25mM:1mL. The stirring is a magnetic stirrer with a speed of 800rpm and the stirring reaction time is 0.5h.

[0035] S30, add the same amount of chloroauric acid solution as in step S10 and stir to form solution D. After the reaction is complete, ultrafilter, centrifuge and wash to obtain gold nanoparticle reinforcing agent.

[0036] In this embodiment of the invention, the ratio of the amount of chloroauric acid solution to deionized water added is 25mM:1mL, the stirring is magnetic stirring at a speed of 800rpm, the stirring reaction time is 0.5h, and when obtaining the gold nanoparticle reinforcing agent by ultrafiltration centrifugation, the ultrafiltration centrifugation speed is 3800xg and the time is 10min, and the washing is done by washing twice with deionized water.

[0037] Performance testing: Transmission electron microscopy observation: An appropriate amount of gold nanoparticle reinforcing agent was dissolved in deionized water to prepare a 1 mg / mL solution. 20 μL of this solution was pipetted onto a copper grid, dried, and used to prepare a sample for transmission electron microscopy (TEM) analysis. The sample was then observed using a TEM. Figure 1Transmission electron microscopy (TEM) images of gold nanoparticle enhancers (hereinafter referred to as gold nanoparticle enhancers) prepared according to embodiments of the present invention for magnetic resonance elastography are shown. The results are as follows... Figure 1 The gold nanoparticle enhancer prepared as shown is spherical with a particle size of approximately 68 nm. This result indicates that the gold nanoparticles prepared by the three-step feeding thermal reduction method exhibit good monodispersity and uniform size distribution, with regular particle morphology, clear boundaries, and no obvious agglomeration. The spherical morphology is beneficial for the stable blood circulation and uniform tissue distribution of gold nanoparticles in vivo; while the particle size of approximately 68 nm is within the ideal size range for nanoparticles used in biomedical applications, effectively avoiding rapid filtration clearance by the kidneys and facilitating accumulation in diseased tissues through enhanced osmotic retention effect (EPR effect). Furthermore, the uniform particle size distribution ensures the stability and reproducibility of product performance between batches, providing a reliable nanomaterial basis for subsequent surface functionalization modification and magnetic resonance elastography applications.

[0038] Dynamic Light Scattering Analyzer (DLS) Test: The gold nanoparticle reinforcing agent was placed in deionized water, sonicated for 2 minutes, and then the particle size distribution of the nanoparticles was measured and calculated using a particle size analyzer. Figure 2 The hydration particle size diagram of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention is shown below. Figure 2 The results show that the hydrated particle size of the prepared gold nanoparticle reinforcing agent is around 68 nm, which is highly consistent with the particle size data measured by transmission electron microscopy. This result indicates that the gold nanoparticles prepared in this invention have good dispersion stability in solution, a uniform surface hydration layer, and no obvious aggregation. The consistency between the hydrated particle size and the electron microscopic particle size indicates that the trisodium citrate stabilizer layer modified on the particle surface is thin and uniform, which is beneficial to maintaining the surface plasmon resonance characteristics of the gold nanoparticles and provides good colloidal stability for their subsequent biological applications. In addition, the narrow distribution of hydrated particle size further confirms the controllability and repeatability of the three-step feeding preparation process of this invention, ensuring the consistency of the in vivo and in vitro behavior of different batches of products, and providing a reliable quality control standard for nanomaterials for magnetic resonance elastography applications.

[0039] Absorbance curve test: The gold nanoparticle reinforcing agent was prepared at a concentration of 500 μg / mL in 2 mL, and its absorbance was measured using a UV-Vis spectrophotometer. Figure 3 The absorbance curves of the gold nanoparticle reinforcing agent prepared according to embodiments of the present invention are shown below. Figure 3 The material exhibits a gold-related absorption peak (absorption peak at 526 nm).

[0040] Fourier transform infrared spectroscopy test: 1 mg of gold nanoparticle reinforcing agent was vacuum dried, and a sample was prepared by mixing it with potassium bromide at a ratio of 1:99. The infrared absorption peak of the gold nanoparticle reinforcing agent was detected by Fourier transform infrared spectroscopy. Figure 4 The Fourier transform infrared spectrum of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention is shown. Characteristic peaks specific to gold appear in the infrared spectrum of the prepared gold nanoparticle reinforcing agent. This confirms the successful reduction of gold and the formation of nanoparticles. Simultaneously, the characteristic peaks of the trisodium citrate-related functional groups in the spectrum indicate that the stabilizer is effectively modified on the particle surface, providing good steric stability and biocompatibility for the gold nanoparticles. Figure 3 and Figure 4 The characterization results corroborate each other, jointly proving that the gold nanoparticle reinforcing agent prepared by the three-step feeding method of this invention has a clear chemical composition, controllable nanostructure and excellent surface properties, laying a reliable material basis for its application in magnetic resonance elastography.

[0041] Biosafety experiments: Prepare a 96-well plate, mainly divided into 6 rows and 6 columns, with 6 wells per group. Add 1×10 to each well. 4 Personal umbilical vein endothelial cells (Huvec cells) were cultured for 24 hours in a 37°C incubator containing 5% CO2. After 24 hours, they were divided into six groups with concentrations of 0 μg / mL, 10 μg / mL, 20 μg / mL, 40 μg / mL, 80 μg / mL, and 160 μg / mL. Except for the NC group, the other groups were given drugs as required and then placed in an incubator for 24 hours. After 24 hours, the material was aspirated, and MTT and pure DMEM were mixed at a ratio of 1:4 (protected from light). 100 μL of the mixture was added to each well of the cell culture plate. After 3 hours, the mixture was aspirated, and 150 μL of dimethyl sulfoxide was added to each well. The plate was shaken for 10-15 minutes, and the data were then calculated and plotted using a computer. Figure 5 The diagram shows the experimental results of the cell biocompatibility of the gold nanoparticle enhancer prepared according to an embodiment of the present invention. The results are as follows... Figure 5 As shown, as the concentration of gold nanoparticles increased from 10 μg / mL to 160 μg / mL, the cell viability fluctuated but remained above 75%. This indicates that the gold nanoparticle enhancer prepared in this invention exhibits extremely low toxicity to HUVEC cells across a range of low to high concentrations, demonstrating good biocompatibility. This provides safety support for its subsequent clinical translation (such as intravenous injection for magnetic resonance elastography), demonstrating the excellent biocompatibility of gold nanoparticles.

[0042] Hemolysis test: Blood was collected from mice, and blood cells were obtained by centrifugation. Gold nanoparticle enhancers were diluted to nine equal concentrations (1: 200 μg / mL, 2: 100 μg / mL, 3: 50 μg / mL, 4: 25 μg / mL, 5: 12.5 μg / mL, 6: 6.25 μg / mL, 7: 3.12 μg / mL, 8: 1.56 μg / mL, 9: 0.78 μg / mL, 10: Positive control, 11: Negative control). These were mixed with PBS solution containing blood cells at a specific ratio and incubated for 2-3 hours. Hemolysis of the gold nanoparticles was observed by centrifugation, and the hemolysis rate was calculated using an ELISA reader. Figure 6 The graph shows the hemolysis rate test results of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention. The results are as follows: Figure 6 As shown, gold nanoparticles exhibit good biocompatibility. Figure 6 The hemolysis rate experiment visually demonstrated the blood compatibility advantages of the gold nanoparticle enhancer of this invention: the horizontal axis represents the different concentrations of gold nanoparticle treatment groups (groups 1-9, with concentration gradients covering 0.78-200 μg / mL), the positive control group (group 10), and the negative control group (group 11), and the vertical axis represents the hemolysis rate (%). The results showed that the hemolysis rate of all gold nanoparticle concentration groups remained at an extremely low level, while the hemolysis rate of the positive control group was close to 100%. This result proves that the gold nanoparticle enhancer prepared in this invention has no significant destructive effect on erythrocyte membranes across the entire tested concentration range, exhibiting excellent blood compatibility. Combined with the previous cytotoxicity experiment results, this further corroborates its good in vivo biocompatibility, providing crucial blood compatibility data support for subsequent clinical translation applications (especially in magnetic resonance elastography scenarios requiring contact with blood circulation).

[0043] Magnetic resonance elastography: Six 5-week-old female SD rats were randomly divided into two groups: the NC group and the Au NPs group, with three rats in each group. The NC group received an injection of gold nanoparticles via the tail vein at a concentration of 2.5 mg / kg. Changes in liver elastography in the SD rats were observed at 0h, 0.5h, 1h, and 2h, and compared with the control group to determine the imaging effect of the gold nanoparticles. Figure 7 The magnetic resonance elastography (MRE) image of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention is shown, wherein, Figure 7 In the image, (a) represents the magnetic resonance grayscale image. Figure 7(b) in the image represents a pseudo-color image from magnetic resonance elastography (MRI). The grayscale images show the MRI grayscale imaging results of the liver of SD rats at different time points (0h, 0.5h, 1h, 2h). The grayscale differences in the liver in the images reflect the distribution of the tissue's physical properties. By comparing the grayscale changes in the NC group (without gold nanoparticles) and the Au NPs group (with gold nanoparticles), the effect of gold nanoparticles on liver tissue signal can be preliminarily observed. Figure 7 (a) shows that the Au NPs group exhibited characteristic changes in liver signal at specific time points after injection, suggesting that gold nanoparticles may have altered the magnetic resonance response characteristics of liver tissue. Meanwhile, the pseudo-color images of magnetic resonance elastography visually represent the elastic distribution of liver tissue (i.e., the spatial differences in tissue stiffness / softness) through color coding. By comparing the pseudo-color images at different time points and between groups, the dynamic changes in liver elasticity after gold nanoparticle injection can be observed. Figure 7 (b) shows that the area or intensity of the highly elastic region in the liver of the Au NPs group changed regularly over time after injection, indicating that gold nanoparticles can specifically affect the elastic response of liver tissue, thereby reflecting their regulation of the liver microenvironment or cell state. Figure 8 This diagram shows the quantitative results of the elastic modulus of the gold nanoparticle reinforcing agent prepared according to an embodiment of the present invention during magnetic resonance elastography. Figure 7 and Figure 8 It is evident that gold nanoparticle enhancers, as contrast agents in magnetic resonance elastography (MRI), significantly enhance the elastic signal differences in liver tissue, resolving the issues of insignificant tissue elasticity differences and insufficient imaging contrast in traditional elastography. By imaging at multiple time points (0h, 0.5h, 1h, and 2h), the dynamic distribution and metabolic processes of gold nanoparticle enhancers within the liver can be observed, providing a visual basis for studying the pharmacokinetics and tissue interactions of nanoparticles. Previous cytotoxicity and hemolysis experiments have confirmed the excellent biosafety of gold nanoparticles, while MRI experiments further demonstrate their effectiveness and practicality in liver elastography in live animals (SD rats), providing crucial in vivo validation data for the subsequent application of gold nanoparticles in the precise diagnosis of liver diseases.

[0044] In summary, this invention provides a gold nanoparticle enhancer for magnetic resonance elastography (MRI), its preparation method, and its applications. In the embodiments of this invention, trisodium citrate is used as a reducing agent and stabilizer, and chloroauric acid solution is added in batches to achieve the controllable synthesis of the gold nanoparticle enhancer. This preparation method is simple, highly operable, and reproducible. The resulting gold nanoparticle enhancer has uniform particle size, good dispersibility, and excellent stability, making it easy to scale up for production. More importantly, the gold nanoparticle enhancer prepared by this invention exhibits excellent low toxicity and good biocompatibility. Cell experiments and hemolysis experiments have confirmed its good biocompatibility. Simultaneously, its tunable stiffness characteristics can effectively enhance the propagation efficiency of mechanical waves in tissues, improve the phase signal-to-noise ratio of MRI, and significantly improve imaging results. Animal experimental results show that after tail vein injection, this gold nanoparticle enhancer can significantly enhance the MRI effect of the liver in SD rats, effectively improving the quantitative diagnostic ability of MRE for early lesions, and has broad clinical application prospects in the early diagnosis of diseases such as liver fibrosis and tumors.

[0045] It should be noted that, for the sake of simplicity, the foregoing embodiments are all described as a series of actions. However, those skilled in the art should understand that the present invention is not limited to the described order of actions, as some steps may be performed in other orders or simultaneously according to the present invention. Furthermore, those skilled in the art should also understand that the embodiments described in the specification are preferred embodiments, and the actions and modules involved are not necessarily essential to the present invention.

[0046] It should be understood that the disclosed apparatus can be implemented in other ways, given the several embodiments provided in this application. For example, the apparatus embodiments described above are merely illustrative; the division of units described above is only a logical functional division, and in actual implementation, there may be other division methods. For example, multiple units or components may be combined or integrated into another system, or some features may be ignored or not executed. Furthermore, the coupling or communication connections shown or discussed may be through some interfaces; the indirect coupling or communication connections between devices or units may be telecommunications or other forms.

[0047] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit the scope of protection of the invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on these embodiments, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art can still combine, add, delete, or otherwise adjust the features of the various embodiments of the present invention according to the circumstances without conflict or creative effort, thereby obtaining different technical solutions that do not fundamentally depart from the concept of the present invention. These technical solutions also fall within the scope of protection of the present invention.

Claims

1. A method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography, characterized in that: The method includes: S10, take trisodium citrate, dissolve trisodium citrate in deionized water to obtain solution A, boil and stir solution A, then add chloroauric acid solution to generate solution B; S20, when the temperature of solution B drops to 90℃, add the same amount of chloroauric acid solution as in step S10 to form solution C and stir; S30, add the same amount of chloroauric acid solution as in step S10 and stir to form solution D. After the reaction is complete, ultrafilter, centrifuge and wash to obtain gold nanoparticle reinforcing agent.

2. The method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography as described in claim 1, characterized in that: In step S10, the ratio of the amount of trisodium citrate to deionized water added is 2.2 mM: 150 mL; the ratio of the volume of deionized water in solution A to the volume of deionized water in solution B is 150:

1.

3. The method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography as described in claim 2, characterized in that: In solution B, the ratio of chloroauric acid solution to deionized water is 25 mM: 1 mL.

4. The method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography as described in claim 2, characterized in that: In step S10, when boiling and stirring solution A, the stirring is magnetic stirring at a speed of 800 rpm.

5. The method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography as described in claim 2, characterized in that: In step S20, the ratio of the amount of chloroauric acid solution to deionized water added is 25 mM: 1 mL; the stirring is magnetic stirring at a speed of 800 rpm, and the stirring reaction time is 0.5 h.

6. The method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography as described in claim 5, characterized in that: In step S30, the ratio of the amount of chloroauric acid solution to deionized water added is 25 mM: 1 mL, the stirring is magnetic stirring at a speed of 800 rpm, and the stirring reaction time is 0.5 h.

7. The method for preparing gold nanoparticle reinforcing agents for magnetic resonance elastography as described in claim 6, characterized in that: In step S30, when obtaining the gold nanoparticle reinforcing agent by ultrafiltration centrifugation, the rotation speed of the ultrafiltration centrifugation is 3800 x g and the time is 10 min. During washing, deionized water is used to wash twice.

8. A gold nanoparticle reinforcing agent for magnetic resonance elastography, prepared by the method for preparing a gold nanoparticle reinforcing agent for magnetic resonance elastography as described in any one of claims 1-7.

9. The use of the gold nanoparticle enhancer for magnetic resonance elastography as described in claim 8 in the preparation of magnetic resonance elastography sensitizing agents.

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