Magnetic guided probiotic-nanovesicle complex, and preparation method and application thereof

Abstract

This invention discloses a magnetically guided probiotic-nanovesicle complex, its preparation method, and its applications, relating to the fields of biotechnology and medicine. The complex consists of turmeric-derived nanovesicles (Tur) and magnetically engineered probiotics (EcN@Fe3O4), which are directed to inflamed intestinal regions via an external magnetic field. This system exhibits significant anti-inflammatory and antioxidant effects, accelerates mucosal healing, restores intestinal microbiota balance, and possesses high biocompatibility and low toxicity. This invention provides a novel solution for the treatment of intestinal dysfunction and shows promising therapeutic effects on a range of inflammatory intestinal diseases.

Description

Technical Field

[0001] This invention relates to the fields of biotechnology and pharmaceutical technology, and more specifically, to a magnetically guided probiotic-nanovesicle complex, its preparation method, and its application. Background Technology

[0002] Enteropathy is a defensive response of the intestine to chemotherapy drugs or bacterial infections. Moderate activation of the intestinal immune system can resist exogenous stimuli, but excessive inflammatory damage can lead to disruption of the intestinal mucosal barrier, imbalance of oxidative stress, and dysbiosis, which in turn can cause ulcers, bleeding, and even systemic infections, posing a challenging problem in clinical treatment. Various inflammatory factors (such as TNF-α and IL-1β) and oxidative products (such as ROS) are known to play key roles in the progression of enteropathy. Effective regulation of these pathological factors can help alleviate the disease course, but current methods are insufficient for precise intervention.

[0003] Traditional treatments typically employ a combination of anti-inflammatory drugs and probiotics, but this approach has significant limitations. While anti-inflammatory drugs can inhibit inflammatory factors, their lack of intestinal targeting and systemic exposure can lead to liver and kidney toxicity. Probiotic preparations, while capable of regulating gut microbiota, face natural barriers from gastric acid and bile, as well as limitations in intestinal colonization, hindering their effectiveness. Even when used in combination, a synergistic effect is difficult to achieve, resulting in limited efficacy. Therefore, researchers are considering designing delivery systems, including nanocarriers, to improve treatment outcomes by leveraging intestinal pathological characteristics. Nanocarriers can enhance local concentrations through intestinal retention, and their encapsulated active ingredients can be released under the stimulation of the inflammatory microenvironment. However, existing nanocarriers have significant drawbacks: conventional carriers such as liposomes have low targeting efficiency and low accumulation rates at inflammatory sites; while cell membrane biomimetic carriers retain some biological activity, the recombination process leads to the loss of probiotic metabolic function; and synthetic magnetic carriers can induce intestinal oxidative stress, exacerbating mucosal damage. In addition, in the complex gastrointestinal environment, these systems cannot solve problems such as premature leakage of active ingredients, low survival rate of probiotics, and difficulty in large-scale preparation, which greatly limits their application in the treatment of intestinal dysfunction.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] The purpose of this invention is to provide a magnetically guided probiotic-nanovesicle complex, its preparation method, and its application. This complex can be directed to inflamed intestinal regions through an external magnetic field, thereby improving the therapeutic effect and achieving efficient and safe treatment.

[0006] This invention is implemented as follows: In a first aspect, the present invention provides a magnetically guided probiotic-nanovesicle complex, the complex comprising turmeric-derived nanovesicles and magnetically engineered probiotics, wherein the magnetically engineered probiotics are formed by the binding of probiotics and Fe3O4 nanoparticles through 3,4-dihydroxyphenylalanine, and the turmeric-derived nanovesicles are bound to the surface of the magnetically engineered probiotics through the 3,4-dihydroxyphenylalanine.

[0007] Secondly, the present invention provides a method for preparing a magnetically guided probiotic-nanovesicle complex, comprising the following steps: Fe3O4 nanoparticles were blended with 3,4-dihydroxyphenylalanine to form a complex. The probiotics and the complex were incubated at 35-40 °C for 2-4 h to form magnetically engineered probiotics. Magnetic engineered probiotics and turmeric-derived nanovesicles were incubated at room temperature for 2-4 hours to form a probiotic-nanovesicle complex.

[0008] Thirdly, the present invention provides the application of a magnetically guided probiotic-nanovesicle complex in the preparation of a medicament for treating intestinal dysfunction.

[0009] The present invention has the following beneficial effects: This invention provides a magnetically guided probiotic-nanovesicle complex and its applications. This system, through multi-level assembly mediated by 3,4-dihydroxyphenylalanine, solves the problems of low gastric acid survival rate and poor bioavailability of active ingredients in traditional probiotics. The complex formulation demonstrated a 75% survival rate in simulated gastric juice after 2 hours, with an average target targeting efficiency improvement of 2.8 times. It overcomes the biocompatibility defects of synthetic magnetic carriers, demonstrating no significant intestinal oxidative stress (MDA levels were not different from the normal group). It achieves synergistic effects of active targeting and microecological regulation, restoring 90% of intestinal villus length in an enteritis model, significantly superior to single probiotic or nanovesicle treatments. The complex has a simple and mild preparation process, is suitable for combinations of various probiotics and plant vesicles, and possesses high versatility and clinical translational potential. Attached Figure Description

[0010] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0011] Figure 1These are scanning electron microscope (SEM) and transmission electron microscope (TEM) images of the EcN@Fe3O4@Tur composite in Example 1 of the present invention. Figure 2 The diagram shows the dynamic migration rate of the EcN@Fe3O4@Tur composite under a 0.5 T magnetic field in Example 1 of this invention. Figure 3 The Shannon index analysis diagrams of gut microbiota in Examples 3 and 4 of this invention are shown. Figure 4 The images show the results of H&E staining of mouse colon tissue sections from Examples 3 and 4 of this invention. Figure 5 The bar chart shows the survival rate of the EcN@Fe3O4@Tur complex in simulated gastric juice (pH 2.0) and 0.3% bile salt solution in Example 5 of this invention. Figure 6 The images show the ELISA detection results of inflammatory factors in Examples 3 and 4 of this invention. Figure 7 This is a graph showing the intestinal permeability test results of Example 3 of the present invention. Detailed Implementation

[0012] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0013] The following is a detailed description of a magnetically guided probiotic-nanovesicle complex proposed in this invention, its preparation method, and its application.

[0014] In a first aspect, the present invention provides a magnetically guided probiotic-nanovesicle complex, the complex comprising turmeric-derived nanovesicles (Tur) and magnetically engineered probiotics (EcN@Fe3O4), wherein the magnetically engineered probiotics are formed by the binding of probiotics and Fe3O4 nanoparticles through 3,4-dihydroxyphenylalanine (DOPA), and the turmeric-derived nanovesicles are bound to the surface of the magnetically engineered probiotics through DOPA, and the entire complex can be directionally delivered by being guided by an external magnetic field.

[0015] Probiotics, as important regulators of the gut microbiota, are widely used in the treatment of intestinal diseases due to their natural biocompatibility and microbiota regulation capabilities. Plant-derived nanovesicles, as natural drug delivery carriers, possess low toxicity, high stability, and the ability to load active ingredients. The combination of these two provides a new synergistic strategy for the treatment of intestinal diseases. In recent years, significant progress has been made in the engineering modification of probiotics (such as surface modification and gene editing) and the extraction and purification of plant nanovesicles (such as differential centrifugation and ultracentrifugation), enabling stable binding of the two through physical or chemical methods. Furthermore, introducing magnetic nanomaterials into this system allows for active targeting using the controllability of an external magnetic field, overcoming the low efficiency of passive targeting in traditional delivery systems. For example, through the coordination of DOPA's catechol groups with Fe3O4 and the covalent binding of amino groups with probiotic surface proteins, a stable magnetic core can be constructed. This core can then be combined with turmeric nanovesicles via electrostatic interactions to form a composite system, preserving the activity of the probiotics while endowing them with magnetic responsiveness.

[0016] The inventors have creatively proposed a magnetically guided probiotic-nanovesicle complex system, avoiding the shortcomings of traditional probiotic preparations such as low gastric acid survival rate (<5%) and poor bioavailability of free active ingredients (curcumin only 0.8-1.2%). Simultaneously, it solves the problem of intestinal oxidative stress (MDA level increased 2.1 times) caused by synthetic magnetic carriers. This invention achieves stable assembly of Fe3O4, probiotics, and nanovesicles through DOPA-mediated multi-level binding, preserving the metabolic activity of probiotics while utilizing the natural protective effect of curcumin vesicles to improve the survival rate in the gastric acid environment (up to 67%). Furthermore, the enrichment rate at inflammatory sites is increased to 78% through external magnetic field guidance, significantly outperforming existing technologies.

[0017] Magnetic nanomaterials are commonly used tools for targeted delivery, and their binding mode with biological carriers directly affects the system's stability and biocompatibility. Fe3O4 is widely used due to its excellent magnetic responsiveness and biocompatibility. DOPA modification can enhance its binding strength with probiotics (loading up to 6-10% w / w) while avoiding the destructive effects of traditional chemical modifications on probiotic activity. In a preferred embodiment of this invention, the Fe3O4 nanoparticles have a particle size of 10-50 nm, a saturation magnetization (Ms) ≥25 emu / g, and can achieve directional migration at 11.5 μm / s under a magnetic field of 0.3-0.5 T, ensuring effective migration in the intestinal fluid environment.

[0018] In an optional implementation, the probiotics are selected from... Escherichia coli Nissle 1917 (EcN) or Lactobacillus rhamnosus GG The Fe3O4 nanoparticles have a particle size of 10-50 nm and a loading of 6%-10% w / w based on the wet cell weight.

[0019] Furthermore, the selection of probiotics needs to consider both intestinal colonization ability and safety. EcN, as a GRAS-level strain, has excellent intestinal adhesion ability and anti-inflammatory properties. Its secreted indole-3-acetic acid can synergistically enhance the NF-κB inhibitory effect (inhibition rate up to 82%) with curcumin. In the preferred embodiment of this invention, the probiotic is EcN, but other lactic acid bacteria, bifidobacteria, etc., with intestinal colonization ability can also be selected, as long as they can bind to Fe3O4 through DOPA and exert a regulatory effect on the flora, they are all included within the scope of this claim.

[0020] In an optional embodiment, the turmeric-derived nanovesicles are extracted from turmeric rhizomes sequentially by differential centrifugation and ultracentrifugation, with a particle size of 50-200 nm. The turmeric-derived nanovesicles include curcumin compounds, lipid components, functional proteins, and polysaccharides.

[0021] Fresh turmeric rhizomes are preferred, and the total content of curcumin compounds in turmeric-derived nanovesicles is ≥17.6%.

[0022] Specifically, the extraction method and composition of turmeric-derived nanovesicles, as natural carriers of active ingredients, directly affect their therapeutic efficacy. Nanovesicles extracted from fresh turmeric rhizomes using differential centrifugation (3000 × g, 10 min) and ultracentrifugation (100,000 × g, 1 h) have a particle size of 50-200 nm and contain curcuminoids (total content ≥17.6%), lipid components, functional proteins, and polysaccharides. Among these, curcuminoids exert anti-inflammatory effects by inhibiting the NF-κB pathway, endogenous antioxidant enzymes (SOD activity ≥200 U / mg) can scavenge ROS, and polysaccharides promote the repair of the intestinal mucus layer. The synergistic effect of these multiple active ingredients gives the nanovesicles both therapeutic and protective functions.

[0023] In an optional embodiment, DOPA serves as the linking medium, and its molar ratio with Fe3O4 significantly affects the binding stability. The molar ratio of 3,4-dihydroxyphenylalanine to Fe3O4 nanoparticles is 1.5:(1-3.5), with a preferred ratio of 2.5:1. This ratio ensures a strong binding between Fe3O4 and probiotics while also preserving sufficient binding sites for turmeric vesicles. During the complex preparation process, Fe3O4 and DOPA are first reacted at pH 8.5 to form a Fe3O4-DOPA complex. Then, the complex is incubated with probiotics at 37 °C for 2-4 h, and finally with turmeric vesicles at room temperature for 2-4 h. All three steps are carried out under physiological conditions, avoiding the destruction of biological activity by high temperatures and strong acids or alkalis.

[0024] Secondly, the present invention provides a method for preparing a magnetically guided probiotic-nanovesicle complex, comprising the following steps: Fe3O4 nanoparticles were blended with 3,4-dihydroxyphenylalanine to form a complex (Fe3O4-DOPA). Probiotics were incubated with Fe3O4-DOPA at 35-40 ℃ for 2-4 h to form magnetically engineered probiotics (EcN@Fe3O4). Magnetic engineered probiotics and turmeric-derived nanovesicles were incubated at room temperature for 2-4 hours to form a probiotic-nanovesicle complex.

[0025] Thirdly, the present invention provides the application of a magnetically guided probiotic-nanovesicle complex in the preparation of a medicament for treating intestinal dysfunction.

[0026] The therapeutic mechanism of the magnetically guided probiotic-nanovesicle complex provided by this invention is reflected in four aspects: First, it achieves precise delivery to the site of inflammation through magnetic field guidance (targeting multiple of 7.1×); second, turmeric vesicles and probiotics synergistically inhibit pro-inflammatory factors (IL-1β / IL-6 / TNF-α downregulated ≥70%); third, a dual antioxidant system (ROS clearance rate of 85%) reduces oxidative stress; and fourth, it regulates the microbial community structure (Firmicutes / Bacteroidetes ratio restored to healthy levels) and promotes intestinal barrier repair (ZO-1 / Occludin expression upregulated).

[0027] In an optional implementation, the intestinal dysfunction includes enteritis induced by chemotherapy drugs or caused by bacterial infection.

[0028] In some preferred embodiments, the drug is administered orally or by enema, and after administration, an external magnetic field of 0.1-1.0 T is applied to guide the complex to be directed to the inflamed intestinal region for 30 min-2 h, and the drug also includes pharmaceutically acceptable excipients.

[0029] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0030] Example 1 This embodiment provides a preparation process for a magnetically guided probiotic-nanovesicle complex, including the following steps: The complex was constructed using Escherichia coli Nissle 1917 (EcN) as the probiotic, Fe3O4 nanoparticles (30 nm in diameter) as the magnetic core, and turmeric-derived nanovesicles (Tur) as the coating layer, mediated by DOPA.

[0031] Fe3O4 nanoparticles and DOPA were dissolved in Tris-HCl buffer at pH 8.5 at a molar ratio of 2.5:1 and stirred at room temperature for 2 hours to form stable Fe3O4-DOPA (Zeta potential +23mV).

[0032] Take 1×10⁻⁶ EcN bacterial culture in the logarithmic phase. 9 EcN@Fe3O4 (Fe3O4 loading 8.7% w / w) was obtained by mixing EcN@Fe3O4 (CFU / mL) with Fe3O4-DOPA at a volume ratio of 1:1, incubating on a shaker at 37 °C for 3 h (150 rpm), centrifuging at 4 °C and 5000 × g for 10 min, and washing three times with PBS.

[0033] Fresh turmeric rhizomes were homogenized with PBS at a ratio of 1:5 (w / v), centrifuged at 3000 × g for 10 min, and the supernatant was collected. The supernatant was then ultracentrifuged at 100,000 × g for 1 h. The precipitate was resuspended in PBS to obtain Tur (particle size 120±30 nm, total curcumin content 17.6%).

[0034] EcN@Fe3O4 and Tur according to OD 600 The mixture was prepared at a ratio of 1:0.5 (w / v), allowed to stand at room temperature for 3 h, centrifuged at 5000 × g for 5 min, and washed twice to obtain EcN@Fe3O4@Tur (saturation magnetization 28 emu / g). Characterization of the prepared composite: Transmission electron microscopy image as shown below. Figure 1 The described structure is a complete structure in which Fe3O4 nanoparticles are attached to the surface of EcN and encapsulated by Tur vesicles. The Fe3O4 particles are uniformly distributed on the EcN surface, and the outer layer is a Tur film structure. The migration rate diagram under a 0.5 T magnetic field is shown in the figure. Figure 2 As shown, the complex exhibits a directional migration rate of 11.5 μm / s in simulated intestinal fluid.

[0035] Example 2 This embodiment provides a preparation process for a magnetically guided probiotic-nanovesicle complex. All other aspects are the same as in Example 1, except that the probiotics used are... Lactobacillus rhamnosus GG (LGG) replaces EcN.

[0036] The steps include: Fe3O4 nanoparticles with a particle size of 50 nm were extracted by Tur using sucrose density gradient centrifugation and the complex was constructed via DOPA-mediated synthesis.

[0037] Fe3O4 nanoparticles were mixed with DOPA at a molar ratio of 2.5:1 and reacted at room temperature for 2 h in Tris-HCl buffer at pH 8.5 to form the Fe3O4-DOPA complex.

[0038] Take 1×10⁻⁶ LGG bacterial suspension in the logarithmic growth phase. 9The CFU / mL of the compound was mixed with the Fe3O4-DOPA complex at a volume ratio of 1:1, incubated at 37 °C for 4 h, and washed 3 times to obtain the magnetically engineered probiotic (LGG@Fe3O4).

[0039] After homogenizing fresh turmeric rhizomes, the target layer was collected by sucrose density gradient centrifugation (100,000 × g, 2 h) and dialyzed to obtain Tur (particle size 80-150 nm).

[0040] LGG@Fe3O4 and Tur were mixed at a volume ratio of 1:2, incubated at room temperature for 2 h, and washed twice to obtain a magnetically guided probiotic-nanovesicle complex (LGG@Fe3O4@Tur).

[0041] Example 3: This embodiment provides the application of the complex in a 5-fluorouracil-induced enteromucositis model, using EcN@Fe3O4@Tur prepared in Example 1.

[0042] C57BL / 6 mice were randomly divided into three groups: model group (intraperitoneal injection of 5-FU 150 mg / kg), free drug group (gavage administration of EcN+Tur mixture), and complex group (gavage administration of EcN@Fe3O4@Tur). After gavage administration, a 0.5 T magnetic field was applied to the abdomen of the mice in the complex group for 1 hour, once daily for 7 consecutive days.

[0043] Post-treatment testing indicators: Colon tissue pathology sections, such as... Figure 4 As shown, the intestinal villus structure damage score in the treatment group was only 2.1 ± 0.5, which was much lower than the 4.8 ± 0.7 in the model group, indicating that the complex treatment significantly promoted the repair of the intestinal mucosal structure and reduced the pathological damage to the intestinal tissue.

[0044] Results of TNF-α level detection for inflammatory factor: Figure 6 As shown, the level of pro-inflammatory factor IL-1β in the treatment group was 125±18 pg / mL, which was significantly lower than that in the model group (387±42 pg / mL); at the same time, the level of IL-6 decreased by 68% compared with the model group, demonstrating the highly effective inhibitory effect of the complex on intestinal inflammation.

[0045] Shannon index analysis of gut microbiota, such as Figure 3 As shown, the Shannon index of the treatment group (complex group) was 5.2, which was significantly higher than that of the model group (3.2), indicating that the complex can effectively improve the decline in gut microbiota diversity caused by 5-FU and restore microbiota homeostasis.

[0046] Intestinal permeability test results as follows Figure 7As shown, the FD-4 permeation in the treatment group (35±6 μg / g) returned to the normal level (28±5 μg / g).

[0047] Example 4: This embodiment provides the application of the complex in a Salmonella-induced infectious enteritis model. This embodiment uses EcN@Fe3O4@Tur prepared in Example 1 to evaluate its therapeutic effect on Salmonella infectious enteritis.

[0048] C57BL / 6 mice were fasted for 12 hours and then orally administered Salmonella Typhimurium (1×10⁻⁶). 8 An infectious enteritis model was established using CFU / animal, and the fecal Salmonella load was ≥1×10⁻⁶ after 72 h. 6 CFU / g was considered a successful model. The model mice were randomly divided into 3 groups (n=6). The model group was administered 0.2 mL of PBS per mouse via gavage, and the free mice were administered EcN (1×10⁻⁶ g) via gavage. 9 A mixture of CFU and Tur (0.5 mg) was administered to the complex group via gavage. The complex group received EcN@Fe3O4@Tur containing equal volumes of EcN and Tur. A 0.3 T magnetic field was applied to the abdomen for 1 hour / day after gavage. After 7 days of treatment, the intestinal Salmonella load in the complex group was reduced by 92% compared to the model group. Colonic tissue pathological sections were analyzed as described above. Figure 4 As shown (mucosal injury score decreased to 1.5±0.4), the IL-6 inflammatory factor level test results are as follows: Figure 6 As shown (68% lower than the model group), the Shannon index analysis of gut microbiota was performed with reference to... Figure 3 As shown (from 2.1 to 4.8).

[0049] Example 5: This embodiment provides a stability test for the composite, using EcN@Fe3O4@Tur prepared in Example 1, and assessing its stability by simulating the gastrointestinal environment and long-term storage conditions.

[0050] The simulated gastric fluid was prepared according to the following formula: 2.0 g NaCl was dissolved in 1000 mL deionized water, the pH was adjusted to 2.0 with 1M HCl, and pepsin was added to a final concentration of 3 g / L; the 0.3% bile salt solution was prepared as PBS buffer (pH 7.4) containing 0.3 g porcine bile salts. The complex was suspended in both simulated solutions and incubated at 37 ℃ in a shaker (100 rpm) for 2 h. The viable cell count was then determined using the plate count method.

[0051] The results are as follows Figure 5The results showed that the survival rate of EcN in simulated gastric fluid reached 67% (significantly higher than the 5% of ordinary EcN), and the survival rate in 0.3% bile salt solution was 72% (3.1 times higher than the uncoated group). In the long-term storage experiment, the complex was aliquoted into sterile centrifuge tubes and stored at 4 ℃ in the dark for 30 days. Weekly sampling and testing showed that the viable bacterial count retention rate was 85% (compared to only 32% for ordinary EcN). The curcumin content retention rate was 92% as determined by HPLC. Dynamic light scattering analysis showed that the particle size remained at 200±15 nm (RSD<5%), with no obvious aggregation.

[0052] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A magnetically guided probiotic-nanovesicle complex, characterized in that, The composite comprises turmeric-derived nanovesicles and magnetically engineered probiotics. The magnetically engineered probiotics are formed by the binding of probiotics and Fe3O4 nanoparticles through 3,4-dihydroxyphenylalanine. The turmeric-derived nanovesicles are bound to the surface of the magnetically engineered probiotics through the 3,4-dihydroxyphenylalanine.

2. The magnetically guided probiotic-nanovesicle complex according to claim 1, characterized in that, The probiotics are selected from Escherichia coli Nissle 1917 or Lactobacillus rhamnosus GG The Fe3O4 nanoparticles have a particle size of 10-50 nm and a loading of 6%-10% w / w based on the wet cell weight.

3. The magnetically guided probiotic-nanovesicle complex according to claim 1, characterized in that, The turmeric-derived nanovesicles are extracted from turmeric rhizomes and have a particle size of 50-200 nm. The turmeric-derived nanovesicles include curcumin compounds, lipid components, functional proteins, and polysaccharides.

4. The magnetically guided probiotic-nanovesicle complex according to claim 1, characterized in that, The molar ratio of 3,4-dihydroxyphenylalanine to Fe3O4 nanoparticles is 1.5:(1-3.5).

5. The magnetically guided probiotic-nanovesicle complex according to claim 1, characterized in that, The saturation magnetization of the complex is ≥25 emu / g, the complex has directional migration ability under the action of an external magnetic field of 0.3-0.5 T, and its enrichment rate at intestinal inflammatory sites is ≥78%.

6. A method for preparing a magnetically guided probiotic-nanovesicle complex as described in any one of claims 1-5, characterized in that, Includes the following steps: Fe3O4 nanoparticles were blended with 3,4-dihydroxyphenylalanine to form a complex. The probiotics and the complex were incubated at 35-40 °C for 2-4 h to form magnetically engineered probiotics. Magnetic engineered probiotics and turmeric-derived nanovesicles were incubated at room temperature for 2-4 hours to form a probiotic-nanovesicle complex.

7. The use of a magnetically guided probiotic-nanovesicle complex as described in any one of claims 1-5 in the preparation of a medicament for treating intestinal dysfunction.

8. The application according to claim 7, characterized in that, The bowel dysfunctions include enteritis induced by chemotherapy drugs or caused by bacterial infection.

9. The application according to claim 7, characterized in that, The drug is administered orally or via enema. After administration, an external magnetic field of 0.1-1.0 T is applied to guide the complex to be delivered directionally to the inflamed intestinal region. The duration of the magnetic field application is 30 min-2 h.

10. The application according to claim 7, characterized in that, The drug also includes pharmaceutically acceptable excipients.

Images