Preparation method and application of Bi2S3 nanoprobe
By preparing Bi2S3 nanoprobes, the problems of complex synthesis and functional imbalance of nanomaterials have been solved, enabling efficient CT imaging and photothermal therapy. These probes possess good biocompatibility and low-cost production, making them suitable for multifunctional integrated diagnostic and therapeutic applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-22
- Publication Date
- 2026-04-03
AI Technical Summary
When using existing nanomaterials to achieve multifunctional diagnosis and treatment, the synthesis steps are complex and time-consuming, and it is difficult to balance diagnostic sensitivity and therapeutic effect. Traditional materials have limitations in imaging and treatment.
Bi2S3 nanoprobes were prepared by chemical synthesis, exhibiting uniform particle size distribution, good biocompatibility, and photothermal effect. By controlling the particle size and charge through surface modifiers, they can achieve functions such as CT imaging, photothermal therapy, and drug delivery.
A simplified, integrated diagnostic and therapeutic nanoplatform has been developed, featuring high-sensitivity imaging and synergistic therapeutic effects, low production costs, good repeatability, and suitability for large-scale production.
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Figure CN121778779A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical materials technology, specifically to a method for preparing Bi2S3 nanoprobes and their applications. Background Technology
[0002] With the continuous development of nanotechnology in the biomedical field, "integrated diagnosis and treatment" has become an important research direction in cancer treatment—that is, the need to construct a nanoscale platform capable of simultaneously achieving highly sensitive diagnosis and effective treatment, real-time monitoring of disease status and treatment effects, reducing the toxic side effects of traditional "one-size-fits-all" treatments, and improving the level of personalized treatment. However, in most previous studies, multiple nanomaterials needed to be integrated into the same platform to achieve multifunctionality. This not only increased the synthesis steps, time consumption, and potential toxicity, but also made it difficult to balance diagnostic sensitivity and treatment efficacy. Therefore, there is an urgent need to develop nanomaterials that combine diagnostic and therapeutic functions and are easy to synthesize.
[0003] While traditional nanomaterials, such as gold nanoparticles, can be used in CT or photoacoustic imaging, their X-ray attenuation coefficients are lower than those of bismuth, resulting in lower imaging contrast at the same concentration. Iron oxide nanoparticles are only suitable for magnetic resonance imaging and cannot achieve multimodal imaging. Furthermore, they are susceptible to the influence of tissue magnetic fields, leading to signal distortion. Bismuth (Bi) has an atomic number of 83. Theoretically, its X-ray absorption capacity is stronger than that of iodine, and bismuth compounds have good biocompatibility, avoiding the toxicity problems of most heavy metals. Secondly, bismuth sulfides are semiconductors with a band gap energy of 1.33 eV and strong absorption capacity in the near-infrared (NIR) region, effectively converting light energy into heat energy, possessing the potential for photothermal therapy (PTT) and enabling a "diagnosis-treatment" function without the need for additional integrated photothermal agents. Moreover, compared with heavy metal nanomaterials such as gold and platinum, bismuth sulfides have higher cost-effectiveness and industrial production potential. Therefore, we propose a method for preparing Bi₂S₃ nanoprobes and their applications. Summary of the Invention
[0004] The purpose of this invention is to provide a method for preparing Bi2S3 nanoprobes and their applications, which have the advantages of small and uniform particle size distribution, good biocompatibility, good photothermal properties and low preparation cost, and solve the limitations of some commonly used inorganic nanomaterials in the prior art.
[0005] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing Bi2S3 nanoprobes and their application, wherein the nanomaterial is prepared by chemical synthesis, has a uniform hydrated particle size distribution, and the hydrated particle size D90 value is between 100-150 nm, and simultaneously possesses good biocompatibility and photothermal effect.
[0006] Preferably, the specific surface area of the nanomaterial is not less than 50 m². 2 / g, with a negatively charged surface and a Zeta potential of -10mV to -40mV.
[0007] A method for preparing Bi2S3 nanomaterials includes the following steps: S1. Separate dissolution of bismuth source and sulfur source: The bismuth source compound is dissolved in a first solvent, and the sulfur source compound is dissolved in a second solvent to obtain a bismuth source solution and a sulfur source solution; the first solvent and the second solvent may be the same or different; S2. Mixing and reaction: Mix the sulfur source solution and bismuth source solution, transfer the mixture to a closed reaction vessel, and react at 120-200°C for 1-24 hours; S3. Post-processing: After the reaction is complete, the product is cooled, washed, and dried to obtain the Bi2S3 nanomaterial.
[0008] Preferably, the bismuth source is selected from at least one of bismuth nitrate pentahydrate (Bi(NO3)3·5H2O), bismuth trichloride (BiCl3), and triphenylbismuth. The sulfur source is selected from at least one of sodium sulfide nonahydrate (Na2S·9H2O), thiourea (CH4N2S), and dibenzyl disulfide.
[0009] Preferably, a surface modifier is also added in step S1 or step S2; The surface modifier is selected from at least one of polyvinylpyrrolidone (PVP K15-K30), polyethylene glycol (PEG 4K), oleic acid (OA), and cetyltrimethylammonium bromide (CTAB).
[0010] Preferably, the reaction in step S2 is a hydrothermal reaction, a solvothermal reaction, or a coprecipitation reaction; By adjusting the reaction temperature, time, reactant concentration, or the type and amount of surface modifier, the hydrated particle size of the obtained Bi2S3 nanomaterials can be controlled within the range of 80-200 nm.
[0011] A drug delivery system comprising the Bi2S3 nanomaterial as a carrier, and a therapeutic drug loaded thereon by physical adsorption or chemical bonding.
[0012] Preferably, the therapeutic drug is a positively charged chemotherapeutic drug; The Bi2S3 nanomaterial adsorbs the chemotherapy drug through electrostatic interaction due to its negative surface charge.
[0013] Application of a Bi2S3 nanomaterial in the preparation of a tumor therapeutic agent, wherein the tumor therapeutic agent is capable of photothermal therapy (PTT).
[0014] Preferably, the tumor treatment agent can synergistically achieve combined treatment with chemotherapy and photothermal therapy.
[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The single-component Bi2S3 nanomaterial obtained by this invention integrates the triple functions of CT imaging contrast agent, photothermal therapy agent and drug carrier, simplifying the design and construction of a diagnostic and therapeutic nanoplatform.
[0016] 2. The preparation method described in this invention has mild conditions, simple steps, and does not require complex equipment. The material properties can be controlled by changing the reaction parameters. It has high repeatability, low production cost, and great potential for large-scale production. Attached Figure Description
[0017] Figure 1 This is a physical image of the Bi2S3 nanomaterial of this invention; Figure 2 The image shows the XRD pattern of the Bi2S3 nanomaterial of this invention. Figure 3 This is a particle size distribution diagram of the Bi2S3 nanomaterial of the present invention; Figure 4 This is a Zeta diagram of the Bi2S3 nanomaterial of this invention; Figure 5 This is a photothermal effect diagram of the Bi2S3 nanomaterial of this invention. Detailed Implementation
[0018] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention.
[0019] Example 1: Dissolution of bismuth and sulfur sources: Add 0.30g Bi(NO3)3·5H2O to 50ml of deionized water, followed by 0.12g CH4N2S. The mixture can be accelerated by slightly heating and stirring for 15min.
[0020] Synthesis of Bi2S3 nanomaterials: The mixture was added to a polytetrafluoroethylene autoclave and reacted at 165°C for 20 h. After naturally cooling to room temperature, the mixture was washed with deionized water and anhydrous ethanol and dried to obtain Bi2S3 nanomaterials.
[0021] Example 2: Dissolution of bismuth and sulfur sources: Add 0.30g Bi(NO3)3·5H2O to 50ml ethanol, followed by 0.12g CH4N2S. Mixing can be accelerated by slightly heating and sonication. Stir for 15min.
[0022] Synthesis of Bi2S3 nanomaterials: The mixture was added to a polytetrafluoroethylene autoclave and reacted at 165°C for 20 h. After naturally cooling to room temperature, the mixture was washed with deionized water and anhydrous ethanol and dried to obtain Bi2S3 nanomaterials.
[0023] Example 3: Dissolution of bismuth and sulfur sources: 0.20 g triphenylbismuth and 0.1 g dibenzyl disulfide were dissolved in 15 ml ethanol and stirred for 30 min. Then, an ethanol solution containing 0.5 g PVP (K15-K30) was added and stirred until homogeneous.
[0024] Synthesis of Bi2S3 nanomaterials: The above mixture was transferred to a polytetrafluoroethylene autoclave and reacted at 180°C for 20 h. After naturally cooling to room temperature, it was washed with deionized water and anhydrous ethanol and dried to obtain Bi2S3 nanomaterials.
[0025] Example 4: Dissolution of bismuth and sulfur sources: 0.20 g triphenylbismuth and 0.1 g dibenzyl disulfide were dissolved in 15 ml ethanol and stirred for 30 min. Then, an ethanol solution containing 0.5 g PEG was added and stirred until homogeneous.
[0026] Synthesis of Bi2S3 nanomaterials: The above mixture was transferred to a polytetrafluoroethylene autoclave and reacted at 180°C for 20 h. After naturally cooling to room temperature, it was washed with deionized water and anhydrous ethanol and dried to obtain Bi2S3 nanomaterials.
[0027] Example 5: Dissolution of bismuth and sulfur sources: (1) Weigh 0.278 g of anhydrous bismuth nitrate and add it to 30 ml of OA. Increase the temperature to accelerate the reaction and form a Bi-OA complex. (2) Dissolve 0.12g Na2S·9H2O in 20ml of water.
[0028] Synthesis of Bi2S3 nanomaterials: The sulfur source in (2) above is added dropwise to (1). The process requires constant stirring. The reaction is carried out at 150°C for 1 hour. After naturally cooling to room temperature, the mixture is washed with deionized water and anhydrous ethanol and dried to obtain Bi2S3 nanomaterials.
[0029] Example 6: Dissolution of bismuth and sulfur sources: (1) Weigh 0.278 g of anhydrous bismuth nitrate and add it to 30 ml of OA. Increase the temperature to accelerate the reaction and form a Bi-OA complex. (2) Dissolve 0.12g Na2S·9H2O in 20ml of water.
[0030] Synthesis of Bi2S3 nanomaterials: The sulfur source in (2) above is added dropwise to (1). The process requires constant stirring. The reaction is carried out at 150°C for 1 hour. After naturally cooling to room temperature, the mixture is washed with deionized water and anhydrous ethanol. The mass of Bi2S3 is calculated according to the wet-dry ratio method. The mixture is dispersed in an appropriate amount of deionized water. Three times the mass of PVP (K15-K30) is added. The mixture is stirred at room temperature for 4 hours. The mixture is then washed with deionized water and anhydrous ethanol and dried to obtain Bi2S3 nanomaterials.
[0031] Example 7: Dissolution of bismuth and sulfur sources: Dissolve 0.15 g BiCl3 and 0.18 g Na2S·9H2O in 60 ml of a 1:1 mixture of water and ethanol containing 0.05 mol / l CATB.
[0032] Synthesis of Bi2S3 nanomaterials: The pH of the mixture was adjusted to around 3 using dilute hydrochloric acid, and then the mixture was refluxed at 80°C for 6 hours. The product was collected by centrifugation, washed with deionized water and anhydrous ethanol, and dried to obtain Bi2S3 nanomaterials.
[0033] Comparative Example 1 (Comparison with traditional imaging materials) Gold nanorods (AuNRs, for CT / photothermal applications) were synthesized following a literature-based method. Characterization revealed that their HU value for CT imaging was only 65% of that of the Bi2S3 nanomaterial of this invention at the same bismuth / gold concentration. At the same near-infrared laser power density, their temperature rise was approximately 15% lower. Furthermore, the synthesis of gold nanorods involves the highly toxic CTAB, raising concerns about their biosafety.
[0034] Comparative Example 2 (Comparison with traditional Bi2S3 preparation methods) A direct precipitation method without surface modification was used (e.g., adding Na2S aqueous solution directly to Bi(NO3)3 acidic aqueous solution). The resulting Bi2S3 particles were of uneven size (50-500 nm), easily agglomerated, with a hydrated particle size PDI greater than 0.3 and a zeta potential close to neutral. They precipitated after being placed in water for several hours and could not effectively load drugs.
[0035] Comparative Example 3 (Comparison with Physical Therapy System) Commercially available Fe3O4 nanoparticles (MRI agent), indocyanine green ICG (photothermal agent), and DOX-loaded liposomes (chemotherapeutic agent) were physically mixed to simulate a traditional composite therapeutic system. Experiments showed that this mixed system exhibited poor stability in in vitro serum, with varying metabolic rates among its components. Furthermore, due to functional segregation, its synergistic therapeutic effect at the cellular and animal levels was significantly lower than that of the single-component Bi2S3-DOX system of this invention.
[0036] Application performance verification The key performance of the Bi2S3 nanomaterials prepared in Examples 1, 3, and 5 of this invention (labeled as BS-1, BS-3, and BS-5, respectively) was compared with that of the materials in Comparative Examples 1 and 2. The results are shown in Table 1.
[0037] Table 1 shows a comparison of key properties of Bi2S3 nanomaterials. ; Furthermore, the combined therapeutic effect of the material of the present invention (taking BS-1-DOX as an example) was evaluated through in vitro cell experiments (CCK-8 assay) and tumor-bearing mouse models, and compared with single treatment methods and the physical hybrid system of Comparative Example 3. As shown in Table 2, the material of the present invention exhibited the highest tumor inhibition rate and the optimal synergistic therapeutic index.
[0038] Table 2 Comparison of in vitro cell killing and in vivo tumor suppression effects ; The above examples and comparative examples fully demonstrate that the Bi2S3 nanomaterials and their preparation method provided by this invention effectively solve the problems of complex construction and limited performance of existing diagnostic and therapeutic nanoplatforms. The prepared materials exhibit excellent properties, and the preparation process is simple and economical. In the field of integrated diagnosis and treatment of tumors, especially in CT imaging-guided chemotherapy-photothermal synergistic therapy, they demonstrate enormous application potential and industrialization value.
[0039] Finally, it should be noted that 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 present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.
Claims
1. A Bi₂S₃ nanomaterial, characterized in that, The nanomaterial is prepared by chemical synthesis. It has a uniform hydrated particle size distribution and a hydrated particle size D90 value between 100-150 nm. It also has good biocompatibility and photothermal effect.
2. The Bi₂S₃ nanomaterial according to claim 1, characterized in that: The specific surface area of the nanomaterial is not less than 50m². 2 / g, with a negatively charged surface and a Zeta potential of -10mV to -40mV.
3. A method for preparing Bi2S3 nanomaterials according to any one of claims 1-2, characterized in that: Includes the following steps: S1. Separate dissolution of bismuth source and sulfur source: The bismuth source compound is dissolved in the first solvent, and the sulfur source compound is dissolved in the second solvent to obtain bismuth source solution and sulfur source solution; S2. Mixing and reaction: Mix the sulfur source solution and bismuth source solution, transfer the mixture to a closed reaction vessel, and react at 120-200°C for 1-24 hours; S3. Post-processing: After the reaction is complete, the product is cooled, washed, and dried to obtain the Bi2S3 nanomaterial.
4. The method for preparing a Bi2S3 nanoprobe according to claim 3, characterized in that: The bismuth source is selected from bismuth pentahydrate, bismuth trichloride, and triphenylbismuth; The sulfur source is selected from sodium sulfide nonahydrate, thiourea, and dibenzyl disulfide.
5. The method for preparing a Bi2S3 nanoprobe according to claim 3, characterized in that: In step S1 or step S2, a surface modifier is also added; The surface modifier is selected from polyvinylpyrrolidone, polyethylene glycol, oleic acid, and hexadecyltrimethylammonium bromide.
6. The method for preparing a Bi2S3 nanoprobe according to claim 3, characterized in that: The reaction described in step S2 is a hydrothermal reaction, a solvothermal reaction, or a coprecipitation reaction; By adjusting the reaction temperature, time, reactant concentration, or the type and amount of surface modifier, the hydrated particle size of the obtained Bi2S3 nanomaterials can be controlled within the range of 80-200 nm.
7. A drug delivery system, characterized in that, The invention comprises the Bi2S3 nanomaterial as described in any one of claims 1-2 as a carrier, and a therapeutic drug loaded thereon by physical adsorption or chemical bonding.
8. The drug delivery system according to claim 7, characterized in that: The therapeutic drug is a positively charged chemotherapy drug; The Bi2S3 nanomaterial adsorbs the chemotherapy drug through electrostatic interaction due to its negative surface charge.
9. An application of the Bi2S3 nanomaterial according to any one of claims 1-2 in the preparation of tumor therapeutic agents, characterized in that: The tumor treatment agent can achieve photothermal therapy.
10. The application of the Bi2S3 nanomaterial according to claim 9 in the preparation of tumor therapeutic agents, characterized in that: The tumor treatment agent can synergistically achieve combined treatment with chemotherapy and photothermal therapy.