Magnetic heat blood vessel and preparation method and application thereof

CN115670787BActive Publication Date: 2026-08-07HUNAN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
HUNAN UNIV
Filing Date
2022-10-20
Publication Date
2026-08-07

AI Technical Summary

Technical Problem

然而依赖抗体识别的集成捕获装置存在成本高以及高转移性循环肿瘤细胞清除能力弱等问题,这将限制集成捕获装置的大规模生产以及治疗效果

Benefits of technology

[0024] (1) This invention provides a method for preparing magnetothermal blood vessels, which is convenient, simple and can be mass-produced; wherein, electrospinning technology is a manufacturing process of doped fibers and surface spraying; secondly, the iron-cobalt graphite nanocapsules doped in this invention are an excellent magnetothermal conversion material with ultra-high saturation magnetization (Ms=197.2emu/g), which is directly proportional to the specific loss power (SLP). Therefore, the magnetothermal blood vessels prepared also have excellent magnetothermal effects. At the same time, since the active cell DNA is easily lost under thermal stimulation, the active cancer cells are naturally susceptible to thermal stimulation and thus die under magnetothermal stimulation.

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Abstract

The application relates to the technical field of biomedical engineering, and provides a magnetocaloric blood vessel as well as a preparation method and application thereof. Silica, ferric nitrate, cobalt nitrate and methanol are mixed, methane is introduced and heated, and iron-cobalt graphite nanocapsules are obtained; polylactic acid, polyethylene oxide, trifluoroethanol and the iron-cobalt graphite nanocapsules are mixed, electrospinning is carried out, and a magnetocaloric fiber membrane is obtained; hyaluronic acid, gelatin, water and N,N-dimethylformamide are mixed, the magnetocaloric fiber membrane is placed on a metal flat plate receiver to carry out electrospinning, and after crosslinking, a magnetocaloric fiber membrane with constructed adhesion sites is obtained; the magnetocaloric fiber membrane with constructed adhesion sites and the magnetocaloric fiber membrane without constructed adhesion sites are stacked on the outer part of a rod core in sequence, and the rod core is removed to obtain the magnetocaloric blood vessel. The magnetocaloric blood vessel provided by the application has a typical bionic structure in structure and mechanical properties, and the death rate of cancer cells on the inner cavity surface after magnetocaloric treatment is as high as 92%.
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Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, and in particular to a magnetothermal blood vessel, its preparation method, and its application. Background Technology

[0002] Circulating tumor cells (CTCs) are a group of cells that detach from tumor lesions and enter the circulatory system. Cancer cells circulating in the blood are one of the main causes of cancer metastasis and recurrence, and there is a significant negative correlation between the number of CTCs in the body and the patient's overall survival rate. Therefore, killing CTCs from the patient's body and reducing their number can alleviate or even prevent metastasis.

[0003] In cancer metastasis, a series of extracellular matrix components (such as extracellular proteins and glycans) participate in the invasion-metastasis cascade of circulating tumor cells (CTCs). The interaction between CTCs and the vascular extracellular matrix is ​​considered an early event in vascular extravasation. In fact, this interaction is regulated by various adhesion factors, such as the metastable adhesion induced between CD44 on the CTC membrane and fibronectin in the extracellular matrix. Therefore, constructing adhesion sites to capture CD44-positive CTCs in the blood is a method targeting highly metastatic CTCs. Currently, integrated capture devices capable of in vivo clearance of CTCs have attracted widespread attention due to their ability to achieve local treatment and avoid systemic toxicity. However, antibody-recognition-dependent integrated capture devices suffer from high costs and weak clearance capacity for highly metastatic CTCs, which limits the large-scale production and therapeutic efficacy of integrated capture devices. Therefore, providing a device with adhesion sites that can be mass-produced and efficiently capture cancer cells is an urgent problem to be solved. Summary of the Invention

[0004] The purpose of this invention is to overcome the problems existing in the prior art and to provide a magnetic thermal blood vessel, its preparation method and application.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] This invention provides a method for preparing a magnetothermal blood vessel, comprising the following steps:

[0007] (1) Mix silicon dioxide, iron nitrate, cobalt nitrate and methanol, and heat with methane to obtain iron-cobalt graphite nanocapsules;

[0008] (2) Polylactic acid, polyethylene oxide, trifluoroethanol and iron cobalt graphite nanocapsules are mixed and electrospun to obtain a magnetothermal fiber membrane.

[0009] (3) Hyaluronic acid, gelatin, water and N,N-dimethylformamide are mixed, and the magnetothermal fiber membrane is placed on a metal plate receiver for electrospinning. After crosslinking, a magnetothermal fiber membrane with adhesive sites is obtained.

[0010] (4) A magnetic thermal fiber membrane with adhesion sites and a magnetic thermal fiber membrane without adhesion sites are sequentially stacked on the outside of the rod core, and the rod core is removed to obtain the magnetic thermal blood vessel.

[0011] Preferably, the mass-to-volume ratio of silicon dioxide, ferric nitrate, cobalt nitrate, and methanol in step (1) is 0.8–1.2 g: 0.135–0.155 g: 0.095–0.115 g: 180–220 mL;

[0012] The flow rate of the methane is 350–450 cm⁻¹. 3 The heating rate is 700–900°C, and the heating time is 4–6 minutes.

[0013] Preferably, the mass ratio of polylactic acid, polyethylene oxide, and trifluoroethanol in step (2) is 3-5:0.5-1.5:93.5-96.5; and the mass fraction of iron-cobalt-graphite nanocapsules in the magnetocaloric fiber is 2.0-7.8%.

[0014] Preferably, in step (2), the voltage of electrospinning is 7-9 kV, the pump flow rate of electrospinning is 0.4-0.6 mL / h, the receiving distance of electrospinning is 14-16 cm, the temperature of electrospinning is 20-30 °C, the humidity of electrospinning is 40-60%, and the roller speed of electrospinning is 1800-2200 rpm.

[0015] Preferably, in step (3), the mass ratio of hyaluronic acid to gelatin is 3.5–4.5:0.5–1.5, the volume ratio of water to N,N-dimethylformamide is 0.5–1.5:0.5–1.5, and the mass-volume ratio of gelatin to water is 0.05–0.15 g:4–6 mL.

[0016] Preferably, the voltage of electrospinning in step (3) is 20-24kV, the pump flow rate of electrospinning is 1.3-1.7mL / h, the receiving distance of electrospinning is 13-17cm, the temperature of electrospinning is 40-50℃, and the humidity of electrospinning is 10-30%.

[0017] Preferably, the area-to-mass ratio of the magnetothermal fiber membrane to the gelatin in step (3) is 529–625 mm². 2 0.5–1.5 mg;

[0018] The crosslinking solution comprises 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, ethanol, and water. The concentration of 1-ethyl-(3-dimethylaminopropyl)carbodiimide in the crosslinking solution is 45–55 mM, and the concentration of N-hydroxysuccinimide in the crosslinking solution is 45–55 mM. The volume ratio of ethanol to water in the crosslinking solution is 3–5:1.

[0019] The crosslinking temperature is 2–6°C, and the crosslinking time is 20–28 h.

[0020] Preferably, the ratio of the magnetothermal fiber membrane with adhesive sites to the magnetothermal fiber membrane without adhesive sites in step (4) is 1:10 to 20 by mass.

[0021] The present invention also provides a magnetothermal blood vessel obtained by the preparation method described above.

[0022] The present invention also provides the application of the magnetic thermal blood vessel in the preparation of a cancer cell removal device.

[0023] The beneficial effects of this invention are:

[0024] (1) This invention provides a method for preparing magnetothermal blood vessels, which is convenient, simple and can be mass-produced; wherein, electrospinning technology is a manufacturing process of doped fibers and surface spraying; secondly, the iron-cobalt graphite nanocapsules doped in this invention are an excellent magnetothermal conversion material with ultra-high saturation magnetization (Ms=197.2emu / g), which is directly proportional to the specific loss power (SLP). Therefore, the magnetothermal blood vessels prepared also have excellent magnetothermal effects. At the same time, since the active cell DNA is easily lost under thermal stimulation, the active cancer cells are naturally susceptible to thermal stimulation and thus die under magnetothermal stimulation.

[0025] (2) This invention provides a magnetic thermal blood vessel with typical biomimetic structure in terms of both structure and mechanical properties. The magnetic thermal blood vessel is hollow, and a dense and ordered parallel topological structure can be seen on the cross-section and the outer surface of the lumen. The inner surface of the lumen is cross-linked with adhesion sites, and a layer of mesh fiber structure can be seen on the surface. The wall thickness of the constructed magnetic thermal blood vessel is 309.7±17.7μm. In addition, the Young's modulus of the magnetic thermal blood vessel shows a significant difference in the circumferential and axial directions, with 13.8±1.4MPa in the circumferential direction and 0.68±0.18MPa in the axial direction.

[0026] (3) The magnetically heated blood vessel lumen provided by this invention has high hydrophilicity; the contact angle of the unmodified magnetically heated blood vessel is 63.9±1.9°, and that of the modified magnetically heated blood vessel is 33.2±3.7°; furthermore, at 1548cm -1 The absorption band of the NH-related amide bond stretching vibration at 1030 cm⁻¹-1 The ratio of the absorption bands of CO-related carboxyl stretching vibrations increased from 0.96 in the uncrosslinked state to 1.03 in the crosslinked state, and the weight loss rate decreased from 41.1±4.7% in the uncrosslinked state to 25.5±2.9% in the crosslinked state. This indicates that the surface of the magnetothermal blood vessel lumen was modified with a layer of hyaluronic acid and gelatin network structure through chemical crosslinking, which can be understood functionally as the construction of polysaccharide / peptide adhesion sites.

[0027] (4) Compared with polylactic acid blood vessels without magnetothermal material, the magnetothermal blood vessels prepared by the present invention have a significant heating effect under alternating magnetic field. By adjusting the concentration of magnetothermal material in the blood vessel, the heating effect of the magnetothermal blood vessel under the same alternating magnetic field conditions can be effectively adjusted. The higher the concentration of magnetothermal material, the faster the heating rate of the magnetothermal blood vessel. According to the measurement, the heating rate of the magnetothermal blood vessel of the present invention can reach 5℃ / s.

[0028] (5) Compared with polylactic acid blood vessels without magnetothermal materials, the magnetothermal blood vessels prepared in this invention have a large number of cancer cells gathered on the inner surface of the lumen, indicating that the magnetothermal blood vessels with adhesion sites have a significant capture ability for cancer cells in a dynamic environment. After magnetothermal treatment, the cancer cells adhering to the inner surface of the magnetothermal blood vessels die over a large area, with a mortality rate as high as 92%. The simple alternating magnetic field and magnetothermal blood vessels do not cause significant damage to cancer cells. The elimination of cancer cells mainly depends on the high-temperature environment generated by the magnetothermal blood vessels under the alternating magnetic field. Attached Figure Description

[0029] Figure 1 Figure 1 shows the structure and mechanical properties of the magnetothermal blood vessel in Example 1; (a) is an optical microscope structural diagram of the magnetothermal blood vessel in Example 1; (b) is a cross-sectional scanning electron microscope image of the magnetothermal blood vessel in Example 1; (c) is a scanning electron microscope image of the outer surface of the magnetothermal blood vessel in Example 1; (d) is a scanning electron microscope image of the inner surface of the magnetothermal blood vessel in Example 1; (e) is a statistical diagram of the vessel wall of the magnetothermal blood vessel in Example 1; (f) is a stress-strain curve diagram of the magnetothermal blood vessel in Example 1 in the circumferential and axial directions; (g) is a statistical diagram of the Young's modulus of the magnetothermal blood vessel in Example 1 in the circumferential and axial directions.

[0030] Figure 2 The figures show the water contact angles of the magnetothermal vessels and the unmodified adhesion sites in Example 1; where (a) is the water contact angle of the magnetothermal vessels at the unmodified adhesion sites in Example 1; (b) is the water contact angle of the magnetothermal vessels in Example 1; and (c) is a statistical chart of the water contact angles of the magnetothermal vessels in Example 1.

[0031] Figure 3The images show the infrared absorption spectra and time-weight loss curves of the magnetothermal blood vessels before and after crosslinking in Example 1; where (a) is the infrared absorption spectrum of the inner surface of the magnetothermal blood vessels before and after crosslinking in Example 1; and (b) is the time-weight loss curve of the magnetothermal blood vessels before and after crosslinking in Example 1.

[0032] Figure 4 The diagram shows the temperature changes of polylactic acid blood vessels and magnetothermal blood vessels in Example 1 under an alternating magnetic field; where (a) is an infrared thermal image of polylactic acid blood vessels and magnetothermal blood vessels in Example 1 under an alternating magnetic field; and (b) is a temperature rise curve of magnetothermal blood vessels with different concentration gradients in Example 1 under an alternating magnetic field.

[0033] Figure 5 The images show the effects of magnetothermal blood vessels and polylactic acid blood vessels on cancer cells in Example 1; (a) is a bioluminescence imaging image of cancer cells captured by magnetothermal blood vessels and polylactic acid blood vessels in Example 1; (b) is a scanning electron microscope image of the inner surface of the lumen of the magnetothermal blood vessels after capturing cancer cells in Example 1; (c) is a fluorescence image of live and dead cells stained before and after magnetothermal treatment of the magnetothermal blood vessels in Example 1; and (d) is a statistical graph of the survival rates of cancer cells, cancer cells treated with alternating magnetic fields, and cancer cells before and after magnetothermal treatment of the magnetothermal blood vessels in Example 1. Detailed Implementation

[0034] This invention provides a method for preparing a magnetothermal blood vessel, comprising the following steps:

[0035] (1) Mix silicon dioxide, iron nitrate, cobalt nitrate and methanol, and heat with methane to obtain iron-cobalt graphite nanocapsules;

[0036] (2) Polylactic acid, polyethylene oxide, trifluoroethanol and iron cobalt graphite nanocapsules are mixed and electrospun to obtain a magnetothermal fiber membrane.

[0037] (3) Hyaluronic acid, gelatin, water and N,N-dimethylformamide are mixed, and the magnetothermal fiber membrane is placed on a metal plate receiver for electrospinning. After crosslinking, a magnetothermal fiber membrane with adhesive sites is obtained.

[0038] (4) A magnetic thermal fiber membrane with adhesion sites and a magnetic thermal fiber membrane without adhesion sites are sequentially stacked on the outside of the rod core, and the rod core is removed to obtain the magnetic thermal blood vessel.

[0039] In this invention, iron-cobalt graphite nanocapsules are prepared by chemical vapor deposition.

[0040] In this invention, the silicon dioxide is fumed silicon dioxide, the ferric nitrate is ferric nitrate nonahydrate, and the cobalt nitrate is cobalt nitrate hexahydrate.

[0041] In this invention, the preferred mass-to-volume ratio of silicon dioxide, ferric nitrate, cobalt nitrate, and methanol is 0.8–1.2 g: 0.135–0.155 g: 0.095–0.115 g: 180–220 mL, more preferably 0.9–1.1 g: 0.140–0.150 g: 0.100–0.110 g: 190–210 mL, and even more preferably 0.95–1.05 g: 0.143–0.147 g: 0.103–0.107 g: 195–205 mL.

[0042] In this invention, the ultrasonic frequency of the mixture in step (1) is preferably 20-40 kHz, more preferably 25-35 kHz, and even more preferably 28-32 kHz; the ultrasonic time of the mixture is preferably 0.8-1.2 h, more preferably 0.9-1.1 h, and even more preferably 0.95-1.05 h.

[0043] In this invention, after the mixing in step (1) is completed, rotary evaporation, drying and pulverization are carried out in sequence to obtain mixed powder, and then methane is introduced for heating.

[0044] In this invention, rotary evaporation is used to remove methanol. The rotary evaporation temperature is preferably 40–60°C, more preferably 45–55°C, and even more preferably 48–52°C. The rotary evaporation time is preferably 0.5–1.5 h, more preferably 0.7–1.3 h, and even more preferably 0.9–1.1 h. The drying temperature is preferably 70–90°C, more preferably 75–85°C, and even more preferably 77–83°C. The drying time is preferably 8–12 h, more preferably 9–11 h, and even more preferably 9.5–10.5 h.

[0045] In this invention, the flow rate of the methane is preferably 350–450 cm⁻¹. 3 / min, further preferably 370–430 cm 3 / min, more preferably 390-410cm 3 / min; the heating temperature is preferably 700-900℃, more preferably 750-850℃, and even more preferably 770-830℃; the heating time is preferably 4-6min, more preferably 4.5-5.5min, and even more preferably 4.7-5.3min.

[0046] In this invention, after heating in step (1) is completed, cooling, acid etching and washing are performed in sequence, and finally polyoxyethylene (100) stearyl ether is added for ultrasonic pulverization to obtain iron-cobalt graphite nanocapsules.

[0047] In this invention, acid etching is used to corrode the silica on the surface of the particles, and the acid etching reagent is hydrofluoric acid; the washing solution is deionized water and ethanol, and polyoxyethylene (100) stearyl ether is added after washing until neutral; the mass ratio of polyoxyethylene (100) stearyl ether to the mixed powder is preferably 7-9:650-750, more preferably 7.5-8.5:670-730, and more preferably 7.8-8.2:690-710.

[0048] In this invention, the frequency of ultrasonic pulverization is preferably 20-40 kHz, more preferably 25-35 kHz, and even more preferably 28-32 kHz; the time of ultrasonic pulverization is preferably 0.8-1.2 h, more preferably 0.9-1.1 h, and even more preferably 0.95-1.05 h.

[0049] In this invention, the mass ratio of polylactic acid, polyethylene oxide, and trifluoroethanol in step (2) is preferably 3-5:0.5-1.5:93.5-96.5, more preferably 3.5-4.5:0.7-1.3:94-96, and even more preferably 3.7-4.3:0.9-1.1:94.5-95.5; the mass fraction of iron-cobalt-graphite nanocapsules in the magnetocaloric fiber is preferably 2.0-7.8%, more preferably 3.0-6.0%, and even more preferably 4.0-5.0%.

[0050] In this invention, the voltage of electrospinning in step (2) is preferably 7-9 kV, more preferably 7.5-8.5 kV, and even more preferably 7.7-8.3 kV; the pump flow rate of electrospinning is preferably 0.4-0.6 mL / h, more preferably 0.45-0.55 mL / h, and even more preferably 0.47-0.53 mL / h; the receiving distance of electrospinning is preferably 14-16 cm, more preferably 14.5-15.5 cm, and even more preferably 14.7-15.3 cm; the temperature of electrospinning is preferably 20-30°C, more preferably 22-28°C, and even more preferably 24-26°C; the humidity of electrospinning is preferably 40-60%, more preferably 45-55%, and even more preferably 47-53%; the roller speed of electrospinning is preferably 1800-2200 rpm, more preferably 1900-2100 rpm, and even more preferably 1950-2050 rpm.

[0051] In this invention, after electrospinning in step (2), the fibers are peeled off from the rollers with a blade to obtain a magnetothermal fiber membrane, which is then vacuum dried for later use. The drying temperature is preferably 20-30°C, more preferably 22-28°C, and even more preferably 24-26°C. The vacuum degree of the drying is preferably 5-10 Pa, more preferably 6-9 Pa, and even more preferably 7-8 Pa.

[0052] In this invention, the mass ratio of hyaluronic acid to gelatin in step (3) is preferably 3.5–4.5:0.5–1.5, more preferably 3.7–4.3:0.7–1.3, and even more preferably 3.9–4.1:0.9–1.1; the volume ratio of water to N,N-dimethylformamide is preferably 0.5–1.5:0.5–1.5, more preferably 0.7–1.3:0.7–1.3, and even more preferably 0.9–1.1:0.9–1.1; the mass-volume ratio of gelatin to water is preferably 0.05–0.15 g:4–6 mL, more preferably 0.07–0.13 g:4.5–5.5 mL, and even more preferably 0.09–0.11 g:4.7–5.3 mL.

[0053] In this invention, the voltage of electrospinning in step (3) is preferably 20-24 kV, more preferably 21-23 kV, and even more preferably 21.5-22.5 kV; the pump flow rate of electrospinning is preferably 1.3-1.7 mL / h, more preferably 1.4-1.6 mL / h, and even more preferably 1.45-1.55 mL / h; the receiving distance of electrospinning is preferably 13-17 cm, more preferably 14-16 cm, and even more preferably 14.5-15.5 cm; the temperature of electrospinning is preferably 40-50°C, more preferably 42-48°C, and even more preferably 44-46°C; and the humidity of electrospinning is preferably 10-30%, more preferably 15-25%, and even more preferably 17-23%.

[0054] In this invention, the area of ​​the magnetothermal fiber membrane in step (3) to the mass ratio of the gelatin is preferably 529–625 mm². 2 0.5–1.5 mg, more preferably 552.25–600.25 mg. 2 0.7–1.3 mg, more preferably 561.69–590.49 mg 2 : 0.9~1.1mg.

[0055] In this invention, the crosslinking solution comprises 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, ethanol, and water. The concentration of 1-ethyl-(3-dimethylaminopropyl)carbodiimide in the crosslinking solution is preferably 45–55 mM, more preferably 47–53 mM, and even more preferably 49–51 mM. The concentration of N-hydroxysuccinimide in the crosslinking solution is preferably 45–55 mM, more preferably 47–53 mM, and even more preferably 49–51 mM. The volume ratio of ethanol to water in the crosslinking solution is preferably 3–5:1, more preferably 3.5–4.5:1, and even more preferably 3.7–4.3:1.

[0056] In this invention, the product obtained by spinning is immersed in a solution for crosslinking.

[0057] The crosslinking temperature is preferably 2-6°C, more preferably 3-5°C, and even more preferably 3.5-4.5°C; the crosslinking time is preferably 20-28h, more preferably 22-26h, and even more preferably 23-25h.

[0058] In this invention, after crosslinking is completed, ultrapure water is used for washing, preferably more than or equal to 3 times, more preferably more than or equal to 4 times, and more preferably more than or equal to 5 times; after washing, vacuum drying is performed and the product is ready for use; the drying temperature is preferably 20-30°C, more preferably 22-28°C, and more preferably 24-26°C; the vacuum degree of drying is preferably 5-10 Pa, more preferably 6-9 Pa, and more preferably 7-8 Pa.

[0059] In this invention, the mass ratio of the magnetothermal fiber membrane with adhesive sites constructed in step (4) to the magnetothermal fiber membrane without adhesive sites constructed is preferably 1:10 to 20, more preferably 1:12 to 18, and even more preferably 1:14 to 16.

[0060] In this invention, the diameter of the polytetrafluoroethylene rod core in step (4) is preferably 1.8 to 2.2 mm, more preferably 1.9 to 2.1 mm, and even more preferably 2 mm.

[0061] The present invention also provides a magnetothermal blood vessel obtained by the preparation method described above.

[0062] In this invention, the magnetic thermal blood vessel is composed of polylactic acid nanofibers encapsulating iron-cobalt-graphite nanocapsules, forming the main framework structure of the magnetic thermal blood vessel. It has a hollow lumen structure, and neatly arranged fibers can be seen in the cross-section and outer surface of the magnetic thermal blood vessel. The inner surface of the lumen is modified with cross-linked hyaluronic acid and gelatin.

[0063] In this invention, the inner diameter of the magnetothermal blood vessel is preferably 1.8-2.2 mm, more preferably 1.9-2.1 mm, and even more preferably 2 mm; the wall thickness of the magnetothermal blood vessel is preferably 290-310 μm, more preferably 295-305 mm, and even more preferably 300 μm.

[0064] The present invention also provides the application of the magnetic thermal blood vessel in the preparation of a cancer cell removal device.

[0065] In this invention, polylactic acid was purchased from Jinan Daigang Bioengineering Co., Ltd.; polyethylene oxide was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; hyaluronic acid was purchased from Bloomage Biotechnology Co., Ltd.; and gelatin was purchased from Sigma-Aldrich Trading Co., Ltd.

[0066] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0067] Example 1

[0068] 1 g of fumed silica, 0.145 g of ferric nitrate nonahydrate, and 0.105 g of cobalt nitrate hexahydrate were dissolved in 200 mL of methanol. The mixture was sonicated at 30 kHz for 1 h, and then rotary evaporated at 50 °C for 1 h to remove the methanol. The resulting powder was dried at 80 °C for 10 h and then pulverized. 0.5 g of the mixed powder was placed in a tube furnace, and the flow rate of methane gas was controlled at 400 cm⁻¹. 3 / min, heated at 800℃ for 5min, cooled and then etched the silica on the surface of the particles with hydrofluoric acid. The particles were washed with deionized water and ethanol until neutral and then 6mg of polyoxyethylene (100) stearyl ether was added. The particles were ultrasonically pulverized at 30kHz for 1h to obtain iron cobalt graphite nanocapsules.

[0069] Polylactic acid, polyethylene oxide, and trifluoroethanol were mixed to obtain a mixed solution (the mass ratio of polylactic acid, polyethylene oxide, and trifluoroethanol was 4:1:95). Iron-cobalt graphite nanocapsules were added to prepare an electrospinning solution. The electrospinning machine was set with a voltage of 8 kV, a pump flow rate of 0.5 mL / h, a receiving distance of 15 cm, a roller speed of 2000 rpm, a temperature of 25 °C, and a humidity of 50%. After spinning, the fibers were peeled off from the roller with a blade to obtain a magnetocaloric fiber membrane (the mass fraction of iron-cobalt graphite nanocapsules in the magnetocaloric fiber was 7.8%). The membrane was dried at a temperature of 25 °C and a vacuum of 8 Pa before use.

[0070] A mixture of 0.4 g hyaluronic acid and 0.1 g gelatin was dissolved in a mixed solution of 5 mL water and 5 mL N,N-dimethylformamide to prepare an electrospinning solution. A magnetothermal fiber membrane (240×240 mm) was placed on a metal plate receiver. The electrospinning machine voltage was set to 22 kV, the pump flow rate to 1.5 mL / h, the receiving distance to 15 cm, the temperature to 45 °C, and the humidity to 20%. After the electrospinning process, the fiber membrane containing hyaluronic acid and gelatin was immersed in a mixed solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, ethanol, and water. The volume ratio of ethanol to water in the mixed solution was 4:1, and the concentrations of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were 50 mM each. The mixture was crosslinked at 4 °C for 24 h, washed three times with ultrapure water, and dried at 25 °C and 8 Pa under vacuum for later use.

[0071] A magnetothermal fiber membrane with adhesive sites and a magnetothermal fiber membrane without adhesive sites are sequentially stacked on the outside of a polytetrafluoroethylene rod core with a diameter of 2 mm. The mass ratio of the magnetothermal fiber membrane with adhesive sites to the magnetothermal fiber membrane without adhesive sites is 1:15. The magnetothermal blood vessel is obtained by removing the rod core.

[0072] The structure of the magnetothermal blood vessel obtained in this embodiment was observed using an optical microscope, resulting in an optical microscope structural image of the magnetothermal blood vessel, as shown below. Figure 1 As shown in (a); the magnetothermal blood vessel obtained in this embodiment was cut with the observation surface facing upwards, fixed on conductive adhesive, and sputtered with gold for 60 seconds to improve conductivity. The cross-section, outer lumen surface, and inner lumen surface of the magnetothermal blood vessel were observed using a scanning electron microscope (TESCAN) at an accelerating voltage of 3kV, resulting in a cross-sectional scanning electron microscope image of the magnetothermal blood vessel, as shown. Figure 1 (b) shows a scanning electron microscope image of the outer surface of the magnetothermal blood vessel, as shown. Figure 1 (c) shows a scanning electron microscope image of the inner surface of the magnetothermal blood vessel, as shown. Figure 1 As shown in (d); the vessel wall thickness was measured from the scanning electron microscope image using ImageJ software, and a statistical map of the magnetothermal vessel wall was obtained, as shown in [example image]. Figure 1 As shown in (e); from Figure 1 As can be seen from (a)-(e), the magnetothermal blood vessel prepared in this embodiment has a hollow structure. A dense and ordered parallel topological structure can be seen on the cross-section and the outer surface of the lumen. Due to the cross-linking of adhesion sites, a layer of mesh fiber structure can be seen on the inner surface of the lumen. This is due to the electrospinning spraying technology. According to statistics, the wall thickness of the constructed magnetothermal blood vessel is 309.7 μm.

[0073] The mechanical properties of the magnetothermal blood vessel obtained in this embodiment were determined using a tensile testing machine (HYC-2011, Hongjin) equipped with a 50N force sensor. The sample was stretched at a constant speed of 10 mm / min, and the stress-strain curves of the magnetothermal blood vessel in the circumferential and axial directions were obtained, as shown in the figure. Figure 1 As shown in (f); the Young's modulus (MPa) was calculated from the stress-strain curve using Origin software, and statistical graphs of the Young's modulus of the magnetothermal vessel in the circumferential and axial directions were obtained, as shown in the figure. Figure 1 As shown in (g); from Figure 1 (f) and Figure 1 As shown in (g), the stress-strain curves reveal that the magnetothermal blood vessels exhibit significant anisotropy in their mechanical properties, with significant differences in Young's modulus in the circumferential and axial directions. Calculations show that the modulus is 13.8 MPa in the circumferential direction and only 0.68 MPa in the axial direction. These results indicate that the magnetothermal blood vessels possess typical biomimetic structures in both their structure and mechanical properties.

[0074] The contact angle of the loaded water was measured using a measuring device (SDC-200, SinDin) under stable temperature and humidity. The inner surface of the magnetothermal vessel obtained in this embodiment was cut vertically upwards. After fixing the exposed inner surface of the magnetothermal vessel onto a glass slide, 5 μL of deionized water was added, and the contact angle was measured at three different locations. After taking pictures, a horizontal line was set, and the water droplets in the field of view were selected. The software automatically calculated the contact angle. A control experiment was set up, keeping other conditions unchanged, and the magnetothermal vessel obtained in this embodiment was replaced with a magnetothermal vessel without modified adhesion sites. Images of the water contact angle of the magnetothermal vessel without modified adhesion sites were obtained, as shown below. Figure 2 As shown in (a); a photograph of the water contact angle of the magnetothermal blood vessel obtained in this embodiment, as shown in (a). Figure 2 (b) shows the statistical diagram of the water contact angle of the magnetothermal blood vessel, as follows: Figure 2 As shown in (c). From Figure 2 As can be seen from (a)-(c), the magnetothermal blood vessels modified with adhesion sites have a significantly reduced water contact angle. Statistically, the contact angle of the unmodified magnetothermal blood vessel is 63.9°, while that of the modified magnetothermal blood vessel is 33.2°, indicating that the lumen of the modified magnetothermal blood vessel has high hydrophilicity. This is because the main components of the modified adhesion sites are hyaluronic acid and gelatin. These two polysaccharide-peptide molecules have abundant hydroxyl and carboxyl groups in their chemical structure, making them extremely hydrophilic.

[0075] Meanwhile, to verify the successful cross-linking of the constructed adhesive molecules, infrared absorption spectra of the lumen before and after cross-linking were detected using an infrared spectrometer (PlasticAnalyzer, SHIMADZU) in an environment with humidity below 45%, obtaining infrared absorption spectra of the magnetothermal vascular lumen surface before and after cross-linking, such as... Figure 3 As shown in (a), cross-linked and uncross-linked magnetothermal blood vessels were immersed in PBS at 37°C for 30 days. The weight loss rate was calculated on days 0, 1, 3, 5, 7, 10, 20, and 30 according to the equation (weight loss rate (%) = Δm / m0 × 100%, where Δm is the change in mass and m0 is the initial mass value). The time-weight loss rate curves of the magnetothermal blood vessels before and after cross-linking were obtained, as shown in (a). Figure 3 As shown in (b); from Figure 3 From (a), we can obtain that it is 1548cm. -1 The absorption band of the NH-related amide bond stretching vibration at 1030 cm⁻¹ -1 The ratio of the absorption bands of CO-related carboxyl stretching vibrations (A1548 / A1030) increased from 0.96 in the uncrosslinked state to 1.03 in the crosslinked state, indicating the formation of new amide bonds between molecules; from Figure 3As shown in (b), the weight loss rate of the uncrosslinked magnetothermal blood vessel was 41.1%, while that of the crosslinked magnetothermal blood vessel decreased to 25.5%, indicating that the crosslinked magnetothermal blood vessel has higher stability. This also proves that stable chemical bonds are formed after crosslinking. The above data show that the inner surface of the magnetothermal blood vessel is modified with a layer of chemically crosslinked hyaluronic acid and gelatin to form a network structure, which can be understood functionally as a polysaccharide / peptide adhesion site.

[0076] First, the closed-loop circulation device consists of a 50mL plastic tube, a peristaltic pump (INTLLAB), and a conduit (diameter = 3.5mm). The magnetothermal blood vessel obtained in this embodiment is connected to the closed-loop circulation device to ensure a stable and uniform water flow in the magnetothermal blood vessel. Then, the magnetothermal blood vessel is exposed to a 60mm diameter coil, a 340kHz frequency, a magnetic field strength of 22.5kA / m, and a flow rate of 5mL / min. The entire heating process is monitored using an infrared thermal imager (FOTRIC365). To optimize the heating effect of the magnetothermal blood vessel, different concentrations of magnetothermal material are incorporated into it, and the magnetothermal effect is detected using the same method. A control experiment is set up, keeping other conditions unchanged, and the magnetothermal blood vessel obtained in this embodiment is replaced with a polylactic acid blood vessel. Infrared thermal images of the polylactic acid blood vessel and the magnetothermal blood vessel under an alternating magnetic field are obtained, as shown below. Figure 4 As shown in (a); the temperature rise curves of magnetothermal blood vessels with different concentration gradients under an alternating magnetic field, as shown in (a). Figure 4 As shown in (b); from Figure 4 As can be seen from (a) and (b), compared with polylactic acid blood vessels without magnetothermal material, magnetothermal blood vessels have a significant heating effect under alternating magnetic field. By adjusting the concentration of magnetothermal material in the blood vessel, the heating effect of magnetothermal blood vessels under the same alternating magnetic field conditions can be effectively adjusted. The higher the concentration of magnetothermal material, the faster the heating rate of magnetothermal blood vessels. According to measurements, the heating rate of the magnetothermal blood vessels of the present invention can reach 5℃ / s.

[0077] After connecting the magnetothermal blood vessel obtained in this embodiment to a closed-loop circulation device, luciferase-labeled cancer cells were introduced at a concentration of 1.3 × 10⁻⁶. 4 The magnetically heated vessels were added to the system at a density of [cell / mL]. After 120 cycles, the magnetically heated vessels were detached from the system, washed three times with PBS, and then immersed in a 15 mg / mL solution of D-fluorescein potassium salt. The magnetically heated vessels were then imaged using a bioluminescence imaging system (IVIS Lumina Xr). A control experiment was set up, keeping other conditions unchanged, and the magnetically heated vessels obtained in this example were replaced with polylactic acid (PLA) vessels. Bioluminescence images of the PLA vessels and magnetically heated vessels after capturing cancer cells were obtained, as shown below. Figure 5As shown in (a); the lumen of the magnetothermal blood vessel was then exposed and fixed overnight in 2.5% glutaraldehyde at 4°C. The fixative was removed the next day, and the vessel was washed three times with PBS. After routine gradient ethanol dehydration, it was placed in a vacuum drying oven at room temperature for more than 12 hours, then fixed on conductive adhesive. After gold sputtering for 60 seconds to improve conductivity, the surface of the lumen of the magnetothermal blood vessel was observed using a scanning electron microscope (TESCAN) at an accelerating voltage of 3 kV. The resulting SEM image of the surface of the lumen after the magnetothermal blood vessel captured cancer cells is shown below. Figure 5 As shown in (b); from Figure 5 As can be observed in (a) and (b), compared with polylactic acid blood vessels without magnetothermal material, more cancer cells are aggregated on the inner surface of the magnetothermal blood vessel. Scanning electron microscopy reveals a large number of cells adhering to the inner surface of the magnetothermal blood vessel, indicating that the magnetothermal blood vessel with adhesion sites has a significant ability to capture cancer cells in a dynamic environment.

[0078] Finally, the captured cancer cells were killed using magnetothermal technology. The magnetothermal blood vessel was then connected to a closed-loop circulation device and 1.3 × 10⁻⁶ cells were added. 4 Cancer cells at a density of [cell density] / mL were subjected to 120 cycles of alternating magnetic field treatment for 10 minutes to expose the lumen of the magnetothermal blood vessel. The vessel was washed three times with PBS, and 400 μL of serum-free cell culture medium containing calcein (1 μg / mL) and propidium iodide (1 μg / mL) was added. After staining at 37°C for 30 minutes, the staining solution was removed, and the vessel was washed three times with PBS. Live cells (green) and dead cells (red) on the lumen surface were observed using a Nikon laser confocal microscope. Fluorescence images of live and dead cells before and after magnetothermal treatment were obtained, as shown below. Figure 5 As shown in (c); a control experiment was then set up with cancer cells and cancer cells treated with an alternating magnetic field. Statistical analysis was performed to calculate cell activity in each group, resulting in statistical graphs of cancer cell survival rates, cancer cells treated with an alternating magnetic field, and cancer cells before and after magnetothermal treatment of the vascular system. Figure 5 As shown in (d); from Figure 5 As can be observed in (c) and (d), after magnetothermal treatment, cancer cells adhering to the inner surface of the magnetothermal blood vessel die over a large area, with a mortality rate as high as 92%. Furthermore, the alternating magnetic field and the magnetothermal blood vessel alone do not cause significant damage to the cancer cells. This indicates that the elimination of cancer cells mainly depends on the high-temperature environment generated by the magnetothermal blood vessel under the alternating magnetic field.

[0079] Example 2

[0080] 0.9 g of fumed silica, 0.14 g of ferric nitrate nonahydrate, and 0.1 g of cobalt nitrate hexahydrate were dissolved in 190 mL of methanol. The mixture was sonicated at 35 kHz for 0.9 h, and the methanol was removed by rotary evaporation at 55 °C for 1.2 h. The resulting powder was dried at 75 °C for 11 h and then pulverized. 0.5 g of the mixed powder was placed in a tube furnace, and the flow rate of methane gas was controlled at 380 cm⁻¹. 3 / min, heated at 750℃ for 4.5min, cooled and then etched the silica on the surface of the particles with hydrofluoric acid. The particles were washed with deionized water and ethanol until neutral and then 5.5g of polyoxyethylene (100) stearyl ether was added. The particles were ultrasonically pulverized at 35kHz for 0.9h to obtain iron cobalt graphite nanocapsules.

[0081] Polylactic acid, polyethylene oxide, and trifluoroethanol were mixed to obtain a mixed solution (the mass ratio of polylactic acid, polyethylene oxide, and trifluoroethanol was 4.5:1.5:94). Iron-cobalt graphite nanocapsules were added to prepare an electrospinning solution. The electrospinning machine was set with a voltage of 7 kV, a pump flow rate of 0.45 mL / h, a receiving distance of 14.5 cm, a roller speed of 1920 rpm, a temperature of 23 °C, and a humidity of 47%. After spinning, the fibers were peeled off the roller with a blade to obtain a magnetocaloric fiber membrane (the mass fraction of iron-cobalt graphite nanocapsules in the magnetocaloric fiber was 6.5%). The membrane was dried at a temperature of 23 °C and a vacuum of 9 Pa for later use.

[0082] A mixture of 0.45 g hyaluronic acid and 0.12 g gelatin was dissolved in a mixed solution of 5.4 mL water and 5 mL N,N-dimethylformamide to prepare an electrospinning solution. A magnetothermal fiber membrane (235 × 235 mm) was placed on a metal plate receiver. The electrospinning machine was set to a voltage of 21 kV, a pump flow rate of 1.4 mL / h, a receiving distance of 14 cm, a temperature of 43 °C, and a humidity of 18%. After completion, the fibers containing hyaluronic acid and gelatin were... The membrane was immersed in a mixed solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, ethanol, and water, wherein the volume ratio of ethanol to water in the mixed solution was 3.5:1, and the concentrations of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were 48 mM, respectively. It was crosslinked at 3 °C for 23 h, washed 4 times with ultrapure water, and dried at 24 °C and 9 Pa for later use.

[0083] A magnetothermal fiber membrane with adhesive sites and a magnetothermal fiber membrane without adhesive sites are sequentially stacked on the outside of a polytetrafluoroethylene rod core with a diameter of 1.9 mm. The mass ratio of the magnetothermal fiber membrane with adhesive sites to the magnetothermal fiber membrane without adhesive sites is 1:17. The magnetothermal blood vessel is obtained by removing the rod core.

[0084] Using the same testing method as in Example 1, the magnetothermal blood vessel constructed in this example had a wall thickness of 327.4 μm, a circumferential Young's modulus of 13.4 MPa, and an axial Young's modulus of 0.62 MPa; the contact angle of the modified magnetothermal blood vessel was 36.9°; and after crosslinking, it was tested at 1548 cm⁻¹. -1 The absorption band of the NH-related amide bond stretching vibration at 1030 cm⁻¹ -1 The ratio of the absorption bands of CO-related carboxyl stretching vibrations (A1548 / A1030) was 1.01, and the weight loss rate of the magnetothermal blood vessel was 28.4%. The heating rate of the magnetothermal blood vessel could reach 4℃ / s. After magnetothermal treatment, cancer cells adhering to the inner surface of the magnetothermal blood vessel showed large-scale death, with a mortality rate as high as 91%.

[0085] Example 3

[0086] 1.1 g of fumed silica, 0.15 g of ferric nitrate nonahydrate, and 0.11 g of cobalt nitrate hexahydrate were dissolved in 210 mL of methanol. The mixture was sonicated at 25 kHz for 1.1 h, and the methanol was removed by rotary evaporation at 45 °C for 0.8 h. The resulting powder was dried at 84 °C for 9 h and then pulverized. 0.5 g of the mixed powder was placed in a tube furnace, and the flow rate of methane gas was controlled at 430 cm⁻¹. 3 / min, heated at 820℃ for 5.2min, cooled and then etched the silica on the surface of the particles with hydrofluoric acid. The particles were washed with deionized water and ethanol until neutral and then 5g of polyoxyethylene (100) stearyl ether was added. The particles were ultrasonically pulverized at 25kHz for 1.1h to obtain iron-cobalt graphite nanocapsules.

[0087] Polylactic acid, polyethylene oxide, and trifluoroethanol were mixed to obtain a mixed solution (the mass ratio of polylactic acid, polyethylene oxide, and trifluoroethanol was 3.5:0.7:95.8). Iron-cobalt graphite nanocapsules were added to prepare an electrospinning solution. The electrospinning machine voltage was set to 8.5 kV, the pump flow rate to 0.54 mL / h, the receiving distance to 16 cm, the roller speed to 2100 rpm, the temperature to 27 °C, and the humidity to 52%. After spinning, the fibers were peeled off the roller with a blade to obtain a magnetocaloric fiber membrane (the mass fraction of iron-cobalt graphite nanocapsules in the magnetocaloric fiber was 5.8%). The membrane was dried at 26 °C and a vacuum of 6 Pa for later use.

[0088] A mixture of 0.36 g hyaluronic acid and 0.08 g gelatin was dissolved in a mixed solution of 4.8 mL water and 4.4 mL N,N-dimethylformamide to prepare an electrospinning solution. A magnetothermal fiber membrane (245 × 245 mm) was placed on a metal plate receiver. The electrospinning machine was set to a voltage of 23 kV, a pump flow rate of 1.6 mL / h, a receiving distance of 15.5 cm, a temperature of 48 °C, and a humidity of 26%. After completion, the solution containing hyaluronic acid and gelatin was... The fiber membrane was immersed in a mixed solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, ethanol and water, wherein the volume ratio of ethanol to water in the mixed solution was 4.5:1, and the concentrations of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were 54 mM, respectively. It was crosslinked at 5 °C for 25 h, washed three times with ultrapure water, and dried at 27 °C and 6 Pa for later use.

[0089] A magnetothermal fiber membrane with adhesive sites and a magnetothermal fiber membrane without adhesive sites are sequentially stacked on the outside of a polytetrafluoroethylene rod core with a diameter of 2.1 mm. The mass ratio of the magnetothermal fiber membrane with adhesive sites to the magnetothermal fiber membrane without adhesive sites is 1:13. The magnetothermal blood vessel is obtained by removing the rod core.

[0090] Using the same testing method as in Example 1, the magnetothermal blood vessel constructed in this example had a wall thickness of 292 μm, a circumferential Young's modulus of 14.1 MPa, and an axial Young's modulus of 0.77 MPa; the contact angle of the modified magnetothermal blood vessel was 29.5°; and after crosslinking, it was tested at 1548 cm⁻¹. -1 The absorption band of the NH-related amide bond stretching vibration at 1030 cm⁻¹ -1 The ratio of the absorption bands of CO-related carboxyl stretching vibrations (A1548 / A1030) was 1.02, and the weight loss rate of the magnetothermal blood vessel was 22.6%. The heating rate of the magnetothermal blood vessel could reach 3℃ / s. After magnetothermal treatment, cancer cells adhering to the inner surface of the magnetothermal blood vessel showed large-scale death, with a mortality rate as high as 90%.

[0091] As can be seen from the above embodiments, the present invention provides a magnetic thermal blood vessel with a hollow structure. A dense and ordered parallel topological structure is visible on the cross-section and outer surface of the vessel. Due to the cross-linking of adhesion sites, a layer of mesh-like fiber structure is visible on the inner surface of the vessel. The wall thickness of the magnetic thermal blood vessel is 309.7±17.7 μm, and the Young's modulus shows significant differences in the circumferential and axial directions. The modified inner lumen of the magnetic thermal blood vessel has high hydrophilicity. The magnetic thermal blood vessel exhibits a significant heating effect under an alternating magnetic field, with a heating rate reaching 5℃ / s. The magnetic thermal blood vessel with adhesion sites has a significant ability to capture cancer cells under dynamic conditions. After magnetic thermal treatment, the mortality rate of cancer cells adhering to the inner surface of the magnetic thermal blood vessel is as high as 92%.

[0092] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a magnetothermal blood vessel, characterized in that, Includes the following steps: (1) Mix silicon dioxide, iron nitrate, cobalt nitrate and methanol, and heat with methane to obtain iron-cobalt graphite nanocapsules; (2) Polylactic acid, polyethylene oxide, trifluoroethanol and iron cobalt graphite nanocapsules are mixed and electrospun to obtain a magnetothermal fiber membrane. (3) Hyaluronic acid, gelatin, water and N,N-dimethylformamide are mixed, and the magnetothermal fiber membrane is placed on a metal plate receiver for electrospinning. After cross-linking, a magnetothermal fiber membrane with adhesive sites is obtained. (4) A magnetothermal fiber membrane with adhesion sites and a magnetothermal fiber membrane without adhesion sites are sequentially stacked on the outside of the rod core, and the rod core is removed to obtain the magnetothermal blood vessel. In step (3), the area-to-mass ratio of the magnetothermal fiber membrane to the gelatin is 529~625 mm². 2 0.5~1.5mg; The crosslinking solution comprises 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, ethanol, and water. The concentration of 1-ethyl-(3-dimethylaminopropyl)carbodiimide in the crosslinking solution is 45-55 mM, and the concentration of N-hydroxysuccinimide in the crosslinking solution is 45-55 mM. The volume ratio of ethanol to water in the crosslinking solution is 3-5:

1. The crosslinking temperature is 2~6℃, and the crosslinking time is 20~28h; In step (4), the mass ratio of the magnetothermal fiber membrane with the adhesion sites constructed to the magnetothermal fiber membrane without the adhesion sites constructed is 1:10~20.

2. The preparation method according to claim 1, characterized in that, The mass-to-volume ratio of silicon dioxide, ferric nitrate, cobalt nitrate, and methanol in step (1) is 0.8~1.2g: 0.135~0.155g: 0.095~0.115g: 180~220mL; The flow rate of the methane is 350~450 cm⁻¹. 3 The heating rate is 700~900℃, and the heating time is 4~6min.

3. The preparation method according to claim 2, characterized in that, In step (2), the mass ratio of polylactic acid, polyethylene oxide, and trifluoroethanol is 3~5:0.5~1.5:93.5~96.5; the mass fraction of iron-cobalt-graphite nanocapsules in the magnetocaloric fiber is 2.0~7.8%.

4. The preparation method according to claim 3, characterized in that, In step (2), the voltage of electrospinning is 7~9kV, the pump flow rate of electrospinning is 0.4~0.6mL / h, the receiving distance of electrospinning is 14~16cm, the temperature of electrospinning is 20~30℃, the humidity of electrospinning is 40~60%, and the roller speed of electrospinning is 1800~2200rpm.

5. The preparation method according to claim 1, characterized in that, In step (3), the mass ratio of hyaluronic acid to gelatin is 3.5~4.5:0.5~1.5, the volume ratio of water to N,N-dimethylformamide is 0.5~1.5:0.5~1.5, and the mass-volume ratio of gelatin to water is 0.05~0.15g:4~6mL.

6. The preparation method according to claim 5, characterized in that, In step (3), the voltage of electrospinning is 20~24kV, the pump flow rate of electrospinning is 1.3~1.7mL / h, the receiving distance of electrospinning is 13~17cm, the temperature of electrospinning is 40~50℃, and the humidity of electrospinning is 10~30%.

7. The magnetothermal blood vessel obtained by the preparation method according to any one of claims 1 to 6.

8. The application of the magnetothermal blood vessel according to claim 7 in the preparation of a cancer cell removal device.

Citation Information

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