A rare earth organic tetrahedral molecular cage complex and its preparation method and application

Abstract

A rare earth organic tetrahedral molecular cage complex and a preparation method and application thereof are constructed with rare earth europium (III) as the vertex, triphenylamine-derived tripodal β-diketone as the face-directing ligand and 1,10-phenanthroline as the auxiliary ligand. The complex is modified by Pluronic F127 to obtain a composite material containing a rare earth organic tetrahedral molecular cage complex structure, and the application of the composite material as an inner ear drug carrier delivery system in the treatment of inner ear diseases. The complex of the present invention provides a cavity with a suitable capacity for accommodating guest molecules, and has high light efficiency to facilitate the tracing of drug carriers, and can efficiently penetrate the cochlear blood-membrane labyrinth barrier to enter the endolymph, and then be taken up by inner ear sensory cells. The Pluronic F127-modified rare earth cage complex synthesized by the present invention can be used as a safe and efficient inner ear drug delivery carrier, with great clinical value and application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, and in particular to the preparation and application of a rare earth cage-shaped complex capable of efficiently entering the inner ear. Background Art

[0002] Lanthanide-Organic Cages (LOCs) are a kind of molecular cages based on multiple rare earth ions (Ln 3+ ) center with an internal cavity. Rare earth europium (III) complexes have excellent fluorescence properties. For example, in β-diketone rare earth Eu (III) complexes, organic ligands can play an "antenna effect" to sensitize Eu (III) to emit characteristic red light, with linear narrow-band emission peaks, high color purity, and large Stokes shift. At the same time, they have excellent optical properties such as long fluorescence lifetime (microseconds to milliseconds) and high quantum yield. If the excellent optical properties of Eu (III) are combined with the cavity structure of the molecular cage to construct Eu (III)-organic molecular cages, it will have good application prospects in the fields of fluorescent probes, host-guest recognition, bioimaging and optical devices. However, most of the current cage coordination compound research reports focus on transition metal cages, using transition metal ions with fixed coordination numbers and coordination configurations as connecting nodes, and synthesizing transition metal cages of different structures by adjusting the geometric configuration of the ligands and the coordination orientation of the coordination sites. Unlike transition metals, the coordination number and configuration of rare earth ions are complex and difficult to control, making it difficult to synthesize LOCs with specific geometric configurations through molecular self-assembly. In addition, there are challenges in obtaining stable LOCs. There are many factors that affect the stability of LOCs, such as temperature, concentration, counter anions, guest molecules, solvent polarity conditions, and changes in system pH, all of which make LOCs exhibit shortcomings such as poor stereoselectivity and kinetic instability. In addition to the above shortcomings, the process of synthesizing LOCs with high purity and stable crystal structure in large quantities is cumbersome and low in yield, which limits the practical application of LOCs materials, especially LOCs with fluorescent properties have rarely been reported in the field of biomedicine. For the application of LOCs in the field of biomedicine, the biocompatibility and dispersibility of LOCs in water need to be further improved.

[0003] Rare earth organic tetrahedral molecular cages are a type of polyhedron with a relatively simple structure. Compared with polyhedrons of other geometric structures, they are simpler and easier to obtain. According to the position of the linker (ligand), they can be divided into face tetrahedron Ln4L4 and edge tetrahedron Ln4L6. Triphenylamine-derived tripod β-diketone can be used as a face-directing organic ligand to bind to Eu 3+Self-assembly to construct an efficient fluorescent tetrahedral rare earth molecular cage with Eu4L4 structure. Yan Pengfei and others used triphenylamine-derived tripodal β-diketone to construct Eu4L4 fluorescent molecular cage, which has been widely used in circularly polarized chiral memory and volatile amine fluorescent probe recognition, but did not combine the fluorescence properties and cavity to play a comprehensive role. Therefore, overcoming the poor stability of LOCs and improving the biocompatibility and water dispersibility of LOCs, comprehensively utilizing the optical properties and cavity characteristics of fluorescent LOCs, and broadening the potential application of rare earth fluorescent molecular cages in biomedicine has important application value.

[0004] The inner ear is a highly differentiated and very delicate peripheral sensory organ. The treatment of inner ear diseases is limited by the cochlear blood-membrane labyrinth barrier, and it is difficult for drug molecules to enter the endolymph to exert corresponding therapeutic effects. Therefore, successful treatment of inner ear diseases depends on efficient drug delivery carriers. In recent years, more and more reports have been published on encapsulating drugs, genes, proteins, etc. onto nanoparticles and transferring them to the inner ear to observe functional changes, rather than simply studying the penetration of nanoparticles into the inner ear. Rare earth organic tetrahedral molecular cage complexes have suitable cavities that can accommodate guest molecules, and have high photosensitivity to facilitate the tracing of drug carriers. It can be used as a safe and efficient inner ear drug delivery carrier, laying a good foundation for the research and clinical application of inner ear diseases. Summary of the invention

[0005] In order to overcome the shortcomings of poor stability of LOCs, the optical properties and cavity characteristics of fluorescent LOCs are fully utilized to expand the potential application of fluorescent LOCs in the field of biomedicine. The present invention provides a rare earth organic tetrahedron based on Eu(III)-triphenylamine-derived tripodal β-diketone that can be synthesized in batches and has stable crystal form. By introducing 1,10-phenanthroline (phen) with low steric hindrance, high rigidity and planarity as an auxiliary ligand, the stability of the Eu(III) tetrahedral molecular cage is improved through a variety of weak interactions (hydrogen bonds, π-π stacking, etc.), so that it can remain stable in air and aqueous solutions with pH = 1-14. In order to further develop its biomedical applications in cell imaging and as a carrier for inner ear drug delivery, the neutral rare earth europium (III) fluorescent tetrahedral cage complex with stable structure and high photosynthesis efficiency was modified with Pluronic F127 to significantly improve its dispersibility in water and biocompatibility. It also has high-efficiency fluorescence and cavity-loaded drug objects. It is a new type of rare earth organic molecular cage complex with dual functions as a fluorescent tracer and a safe and efficient inner ear drug delivery carrier.

[0006] The purpose of the present invention is to provide a rare earth cage complex (Eu4L4)(phen)4 with a tetrahedral configuration that can efficiently enter the inner ear, as well as a preparation method and application thereof, and a preparation method of a Eu(III)-organic tetrahedral fluorescent molecular cage that can be easily synthesized in batches and has a stable crystal structure. The synthesized organic tetrahedral fluorescent molecular cage is modified with Pluronic F127 to obtain a Eu(III)-organic tetrahedral fluorescent molecular cage with high biocompatibility, good dispersibility in water, and stable fluorescence, which can be used as a safe and efficient inner ear drug delivery carrier with drug tracing function.

[0007] The above-mentioned purpose of the present invention is achieved through the following technical solutions.

[0008] The rare earth organic tetrahedral molecular cage complex (Eu4L4)(phen)4 described in the present invention is characterized by: using rare earth europium (III) as the vertex, triphenylamine-derived tripodal β-diketone (abbreviated as L) as the surface-directing ligand and 1,10-phenanthroline (phen) as the auxiliary ligand to construct a rare earth organic molecular cage complex with a tetrahedral structure. The structure is shown below:

[0009]

[0010] The method for preparing a rare earth organic tetrahedral molecular cage complex described in the present invention comprises the following steps:

[0011] (1) dissolving a triphenylamine-derived tripodal β-diketone and a base in a first organic solvent at a molar ratio of 1:3, and stirring at 25-50° C. until clear;

[0012] (2) dissolving an equimolar amount of EuX3·6H2O (X is an anion) of the tripodal β-diketone derived from triphenylamine in a first organic solvent, and then slowly adding the mixture dropwise to the reaction solution of step (1), maintaining the temperature at 25-50° C., and continuing the reaction for 1-5 hours;

[0013] (3) dissolving 1,10-phenanthroline (phen) in an equal molar amount to the triphenylamine-derived tripodal β-diketone in a first organic solvent, stirring at room temperature until clear, and then adding the mixture to the reaction solution of step (2), maintaining at 25-50° C., and continuing the reaction for 19-23 hours;

[0014] (4) After the reaction is completed, the yellow precipitate obtained in step (3) is separated, and the yellow solid is washed with the first organic solvent and n-hexane respectively, and then vacuum dried to obtain an amorphous rare earth cage complex (Eu4L4)(phen)4.

[0015] (5) Dissolving the amorphous rare earth cage complex (Eu4L4)(phen)4 in a second organic solvent and then diffusing the mixture in a third organic solvent for 1-2 weeks, wherein the volume ratio of the second organic solvent to the third organic solvent is 1:1-1:4, to obtain a rare earth organic tetrahedral molecular cage complex (Eu4L4)(phen)4.

[0016] The structural formula of the tripodal β-diketone derived from the organic ligand triphenylamine is shown in formula (II); the structural formula of phen is shown in formula (III):

[0017]

[0018] The first organic solvent is one of methanol or ethanol. Preferably, the first solvent is methanol.

[0019] The second organic solvent is one of dichloromethane, chloroform or tetrahydrofuran. Preferably, the second organic solvent is dichloromethane.

[0020] The third organic solvent is one of n-hexane, cyclohexane, n-pentane, n-heptane or diethyl ether. Preferably, the third organic solvent is n-hexane.

[0021] The base is one of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, ammonia water or triethylamine. Preferably, the base is sodium hydroxide.

[0022] The anion X is one of nitrate, halide, oxalate, sulfonate, trifluoromethanesulfonate and acetate. Preferably, the anion X is chloride.

[0023] Furthermore, the present invention provides a composite material containing a rare earth organic tetrahedral molecular cage complex ((Eu4L4)(phen)4) structure, wherein the material is obtained after being modified by Pluronic F127 and has the following structure:

[0024]

[0025] The composite material containing the rare earth organic tetrahedral molecular cage complex ((Eu4L4)(phen)4) structure has the characteristics of high biocompatibility, good dispersibility in water, and stable fluorescence. The preparation method thereof comprises the following steps:

[0026] The mass ratio of (Eu4L4)(phen)4 to Pluronic F127 is 1:1-1:5. After being dissolved and clarified with tetrahydrofuran, it is added to deionized water with a volume ratio of tetrahydrofuran to deionized water of 1:1-1:2. Stir at room temperature for 1-5 hours. After dialysis for 12-24 hours, freeze-dry to obtain a yellow solid composite material (Eu4L4)(phen)4@F127. Its synthesis route is shown in the following formula:

[0027]

[0028] The composite material (Eu4L4)(phen)4@F127 containing a rare earth organic tetrahedral molecular cage complex ((Eu4L4)(phen)4) structure described in the present invention is used as an inner ear drug carrier delivery system in the treatment of inner ear diseases.

[0029] The present invention has the beneficial effects:

[0030] The rare earth organic tetrahedral molecular cage complex (Eu4L4)(phen)4 prepared by the present invention has the advantages of simple batch synthesis, stable crystal structure and excellent optical properties. 3+ As the vertices of the tetrahedron, the tripodal β-diketone derived from triphenylamine is used as the main framework of the tetrahedron. By introducing 1,10-phenanthroline (phen) with small steric hindrance, rigidity and high planarity as an auxiliary ligand, it participates in the rare earth Eu 3+ Coordination, so that L and phen are chelated with Eu through O and N coordination sites respectively. 3+ The coordination number reaches 8, and the stability of the Eu(III) tetrahedral molecular cage is effectively improved through a variety of weak interactions (hydrogen bonds, π-π stacking, etc.), so that it can be placed in the air for 30 days and immersed in water at room temperature for 24 hours, and the structure remains stable. It is worth noting that the Eu(III) molecular cage prepared by the present invention remains stable in structure after being immersed in an aqueous solution with a pH of 1-14 for 12 hours, and still maintains a strong characteristic fluorescence of Eu(III).

[0031] The rare earth organic tetrahedral molecular cage complex (composite material (Eu4L4)(phen)4@F127) obtained by modifying (Eu4L4)(phen)4 with Pluronic F127) has high biocompatibility and good dispersibility in water. SEM and TEM results show a uniform spherical morphology, and particle size analysis results show that the average particle size distribution is about 300nm.

[0032] The synthesized rare earth organic tetrahedral molecular cage complex ((Eu4L4)(phen)4) of the present invention provides a cavity with a suitable capacity to accommodate guest molecules, has high light efficiency, is convenient for tracing of drug carriers, and has good biocompatibility. The inner ear is a highly differentiated and very delicate peripheral sensory organ. The treatment of inner ear diseases is limited by the cochlear blood-membrane labyrinth barrier, and it is difficult for drug molecules to enter the endolymph to exert corresponding therapeutic effects. The synthesized rare earth organic tetrahedral molecular cage complex (Eu4L4)(phen)4 of the present invention can efficiently penetrate the cochlear blood-membrane labyrinth barrier to enter the endolymph, and then be taken up by the inner ear sensory cells. It can be used as a safe and efficient inner ear drug delivery carrier to load inner ear related drugs, and has great clinical value and application prospects for the treatment of inner ear diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Schematic diagram of the (Eu4L4)(phen)4 tetrahedral molecular cage cavity structure in the present invention.

[0034] Figure 2 Schematic diagram of the minimum asymmetric unit structure of the tetrahedral molecular cage in the present invention.

[0035] Figure 3 This is the powder diffraction XRD of the (Eu4L4)(phen)4 tetrahedral molecular cage in the present invention.

[0036] Figure 4 This is the acid-base powder diffraction XRD comparison of the (Eu4L4)(phen)4 tetrahedral molecular cage in the present invention at different pH values.

[0037] Figure 5 This is the excitation diagram of (Eu4L4)(phen)4 at different concentrations in toluene in the present invention.

[0038] Figure 6 This is the emission diagram of (Eu4L4)(phen)4 at different concentrations in toluene in the present invention.

[0039] Figure 7 This is the excitation diagram of (Eu4L4)(phen)4@F127 at different concentrations in water in the present invention.

[0040] Figure 8 This is the emission diagram of (Eu4L4)(phen)4@F127 at different concentrations in water in the present invention.

[0041] Fig. 9 This is the scanning electron microscopy of (Eu4L4)(phen)4@F127 in the present invention.

[0042] Fig.10The particle size distribution diagram of (Eu4L4)(phen)4@F127 in the present invention is shown in the figure. The inset is a transmission electron microscopy image.

[0043] Fig.11 : Fluorescence confocal images of (Eu4L4)(phen)4@F127 cells.

[0044] Fig.12 :(Eu4L4)(phen)4@F127 has no effect on the hearing of mice.

[0045] Fig.13 :Distribution of (Eu4L4)(phen)4@F127 in the stria vascularis and basilar membrane of the cochlea.

[0046] Fig.14 :Schematic diagram of its application in the treatment of inner ear diseases. DETAILED DESCRIPTION

[0047] The present invention will be further described by the following embodiments.

[0048] Example 1: Preparation of (Eu4L4)(phen)4 tetrahedral molecular cage.

[0049] The reaction route is as follows:

[0050]

[0051] 4mmol of triphenylamine-derived tripodal β-diketone (L) and 12mmol of NaOH were dissolved in 5mL of methanol and stirred at 25°C until clear; 0.1mmol of EuCl3·6H2O dissolved in 5mL of methanol was slowly added dropwise to the above reaction solution, maintained at 25°C, and continued to react for 1 hour; 0.1mmol of phen was dissolved in 5mL of methanol, stirred at room temperature until clear, and then added to the reaction solution, maintained at 25°C, and continued to react for 23 hours; after the reaction, the yellow precipitate was centrifuged, and the yellow solid was washed twice with methanol and once with n-hexane, and then vacuum dried to obtain an amorphous rare earth cage complex (Eu4L4)(phen)4. The yield was 82.5%.

[0052] Take 0.1 g of the amorphous product and dissolve it in 50 mL of dichloromethane, and diffuse it in n-hexane liquid-liquid for 1 week to obtain a yellow spindle-shaped crystalline rare earth cage complex (Eu4L4)(phen)4 with a yield of 72.3%.

[0053] Through X-ray single crystal diffraction and single crystal structure analysis, the structure of Eu(III) tetrahedral molecular cage complex can be confirmed, such as Figure 1 , 2 and Tables 1 and 2.

[0054] Table 1 (Eu4L4)(phen)4 crystal structure data

[0055]

[0056] Table 2 Weak interaction data in the crystal structure of (Eu4L4)(phen)4

[0057]

[0058]

[0059] Symmetrical codes: b) 3 / 2-x, 1 / 2-y, 2-z; c) 3 / 2-x, -1 / 2+y, 3 / 2-z; d) -1 / 2+x, 1 / 2-y, -1 / 2+z; e) -1 / 2+x, 1 / 2+y, -1+z.

[0060] Single crystal structural analysis shows that the Eu(III) molecular cage complex crystallizes in the monoclinic system, C2 / c space group, and the unit cell parameters are α=90°,β=127.368(1)°,γ=90°,V=20160.0(4). From the crystal structure diagram, we can see that (Eu4L4)(phen)4 has a tetrahedral configuration: 4 Eu 3+ As the vertices of the tetrahedron, four triphenylamine-derived tripodal β-diketone ligands are located on the four faces of the tetrahedron, and four phen auxiliary ligands are respectively attached to the four Eu 3+ Coordination, so that Eu 3+ Satisfies the coordination number of 8, such as Figure 1 , 2. The tetrahedral molecular cage structure is stable, such as Figure 3 , as shown in Figure 4: The molecular cage was placed in air for 30 days and soaked in water at room temperature for 24 hours. The PXRD results showed that the sample was consistent with the simulated XRD comparison, indicating that its structure was stable; after the Eu(III) molecular cage crystal was immersed in different pH aqueous solutions for 12 hours, the sample XRD was consistent with the simulated XRD, indicating that the molecular cage structure has excellent acid and alkali stability. The molecular cage has Eu(III) characteristic fluorescence emission in toluene, such as Figure 5 , as shown in 6.

[0061] Example 2: Preparation of (Eu4L4)(phen)4 tetrahedral molecular cage.

[0062] The reaction route is as in Example 1:

[0063] 7mmol of triphenylamine-derived tripodal β-diketone (L) and 21mmol of KOH were dissolved in 25mL of methanol and stirred at 40°C until clear; 7mmol of Eu(NO3)3·6H2O dissolved in 10mL of methanol was slowly added dropwise to the above reaction solution, maintained at 40°C, and the reaction was continued for 3 hours; 9mmol of phen was dissolved in 10mL of methanol, stirred at room temperature until clear, and then added to the reaction solution, maintained at 40°C, and the reaction was continued for 21 hours; after the reaction was completed, the yellow precipitate was centrifuged, and the yellow solid was washed twice with methanol and once with n-hexane, and then vacuum dried to obtain an amorphous rare earth cage complex (Eu4L4)(phen)4 with a yield of 81.5%.

[0064] 1.5 g of the amorphous product was dissolved in 100 mL of tetrahydrofuran and diffused in cyclohexane for one week to obtain a yellow spindle-shaped rare earth cage complex (Eu4L4)(phen)4 with a yield of 68.5%.

[0065] Example 3: Preparation of (Eu4L4)(phen)4 tetrahedral molecular cage.

[0066] The reaction route is as in Example 1:

[0067] 10mmol of triphenylamine-derived tripodal β-diketone (L) and 30mmol of triethylamine were dissolved in 50mL of ethanol and stirred at 50°C until clear; 10mmol of EuCl3·6H2O dissolved in 10mL of ethanol was slowly added dropwise to the above reaction solution, maintained at 50°C, and the reaction was continued for 5 hours; 10mmol of phen was dissolved in 10mL of ethanol, stirred at room temperature until clear, and then added to the reaction solution, maintained at 50°C, and the reaction was continued for 19 hours; after the reaction was completed, the yellow precipitate was centrifuged, and the yellow solid was washed twice with ethanol and once with n-hexane, and then vacuum dried to obtain an amorphous rare earth cage complex (Eu4L4)(phen)4 with a yield of 80.3%.

[0068] 2 g of the amorphous product was dissolved in 200 mL of tetrahydrofuran and diffused in cyclohexane for 2 weeks to obtain a yellow spindle-shaped rare earth cage complex (Eu4L4)(phen)4 with a yield of 71.2%.

[0069] Example 4: Preparation of (Eu4L4)(phen)4@F127 tetrahedral molecular cage composite material.

[0070] 4 mg (Eu4L4) (phen) 4 and 20 mg Pluronic F127 were dissolved in 5 mL tetrahydrofuran until clear, added into 10 mL deionized water, stirred at room temperature for 1 hour and then dialyzed for 24 hours. After the dialysis was completed, the yellow solid composite material (Eu4L4) (phen) 4@F127 was obtained by freeze-drying with a yield of 76.3%.

[0071] The prepared composite material (Eu4L4)(phen)4@F127 has good dispersibility in water and still maintains Eu 3+ Characteristic fluorescence, such as Figure 7 , as shown in Figure 8. ICP-MS was used to determine the Eu4L4 (phen)4@F127 in a 1 mg / mL aqueous solution. 3+ The content is 30ppm, which is converted into a molar concentration of 5×10 -5 M. SEM and TEM results showed that the dispersed samples in water had a uniform spherical morphology, and the particle size distribution showed that the average size was about 300 nm, as shown in Fig. 9 , as shown in 10. It is worth noting that the dispersion of the composite material in water is significantly improved compared with the unmodified Eu(III) molecular cage, and the fluorescence in water is more uniform. This lays the foundation for potential applications in biomedicine.

[0072] Example 5: Verification of biocompatibility of (Eu4L4)(phen)4@F127 tetrahedral molecular cage composite material.

[0073] HEI-OC1 cells were seeded in a 96-well plate at a density of 2000 cells / well and cultured for 24 hours. The culture medium was removed and fresh culture medium containing caged complex nanocarriers was added at final concentrations of 1, 5, 10, 50, 100, and 200 ug / mL, respectively. Untreated culture medium was used as a control. After 12 hours of culture, the cell viability was determined by the CCK8 kit, and the cell uptake of (Eu4L4)(phen)4@F127 was detected by laser confocal microscopy. The results showed that (Eu4L4)(phen)4@F127 has good biocompatibility, can be taken up by cells, and is concentration-dependent. The CCK8 detection results showed that (Eu4L4)(phen)4@F127 has weak cytotoxicity and good biosafety. Fig.11 shown.

[0074] In vivo (mouse) experiments: different concentrations (10, 50, 100ug / mL) of caged complex nanocarriers were injected into the tail vein, and auditory brainstem potential (ABR) was used to detect the hearing function of mice. In vivo experiments showed that intravenous injection of various concentrations of (Eu4L4)(phen)4@F127 had no significant effect on the hearing of mice. Fig.12The above data show that (Eu4L4)(phen)4@F127 has good biocompatibility.

[0075] Example 6: Detection of dynamic distribution of (Eu4L4)(phen)4@F127 tetrahedral molecular cage complex in the inner ear.

[0076] The (Eu4L4)(phen)4@F127 tracing test was carried out. The caged complex nanocarriers with different concentrations of 100ug / mL were injected into the tail vein, and the auditory brainstem potential (ABR) was used to detect the hearing function of mice. After anesthesia, the mice were killed by dislocation, and the cochlea of ​​the mice was taken out by the end. After being fully fixed with 4% paraformaldehyde, the EDTA was decalcified for 48 hours, and the basilar membrane and vascular striae of the cochlea were carefully separated under a microscope. Immunofluorescence staining was performed to mark the basilar membrane hair cells and cell nuclei. After sealing, the dynamic distribution of (Eu4L4)(phen)4@F127 in the basilar membrane and vascular striae of the cochlea and the fluorescence quantification were detected under laser confocal microscope. The results showed that (Eu4L4)(phen)4@F127 signal (red light) could be detected in the blood vessels of the vascular striae of the cochlea 10 minutes after (Eu4L4)(phen)4@F127 was injected into the tail vein, and it was distributed in the vascular striae tissue 1 hour later. After 1 day of administration, (Eu4L4)(phen)4@F127 signal was detected in the sensory hair cells of the cochlea. After 3 days, the fluorescence signal was slightly weakened, and a weak signal could still be detected after 7 days. Fig.13 As shown. (Eu4L4)(phen)4@F127 can pass through the blood-membrane barrier of the cochlea, enter the endolymph, and be successfully taken up by the cochlear sensory cells, and can be distributed in the sensory cells for a long time. In addition, in the cochlear basilar membrane, the cochlear sensory cells take up (Eu4L4)(phen)4@F127 mainly in the outer hair cells, and the inner hair cells take up less. This lays the foundation for the application of the invention in the treatment of inner ear related diseases, and has broad application prospects in inner ear diseases, such as Fig.14 shown.

Claims

1. A method for preparing a rare earth organic tetrahedral molecular cage complex, wherein the complex has rare earth europium (III) as the vertex and a triphenylamine-derived tripod β -Diketone L is used as the face-directing ligand and 1,10-phenanthroline phen is used as the auxiliary ligand to construct a rare earth organic molecular cage complex with a tetrahedral structure. The structure is shown below: ； Features: The steps include: (1) The triphenylamine-derived tripod was added at a molar ratio of 1:

3. β - Dissolve the diketone L and the base in the first organic solvent and stir at 25-50°C until clear; (2) The tripod derivative of triphenylamine β -EuX3·6H2O in an equal molar amount of diketone L is dissolved in the first organic solvent, and then slowly added dropwise to the reaction solution of step (1), maintained at 25-50°C, and continued to react for 1-5 hours, X is an anion; (3) The tripod derivative of triphenylamine β - Dissolve an equal molar amount of 1,10-phenanthroline phen in the first organic solvent, stir at room temperature until clear, and then add the mixture to the reaction solution of step (2), maintain at 25-50°C, and continue the reaction for 19-23 hours; (4) After the reaction is completed, the yellow precipitate obtained in step (3) is separated, and the yellow solid is washed with the first organic solvent and n-hexane respectively, and then vacuum dried to obtain an amorphous rare earth cage complex (Eu4L4)(phen)4; (5) dissolving the amorphous rare earth cage complex (Eu4L4)(phen)4 in a second organic solvent, and then diffusing the mixture in a third organic solvent for 1-2 weeks, wherein the volume ratio of the second organic solvent to the third organic solvent is 1:1-1:4, to obtain a rare earth organic tetrahedral molecular cage complex (Eu4L4)(phen)4; The first organic solvent is one of methanol or ethanol; The second organic solvent is one of dichloromethane, chloroform or tetrahydrofuran; The third organic solvent is one of n-hexane, cyclohexane, n-pentane, n-heptane or diethyl ether; The base is one of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, ammonia water or triethylamine; The anion X is one of nitrate, halide, oxalate, sulfonate, trifluoromethanesulfonate and acetate.

2. A method for preparing a composite material containing the rare earth organic tetrahedral molecular cage complex structure according to claim 1, wherein the composite material is obtained after being modified by Pluronic F127 and has the following structure: ； It is characterized in that The steps include: The mass ratio of (Eu4L4)(phen)4 to Pluronic F127 is 1:1~1:

5. After being dissolved and clarified with tetrahydrofuran, it is added into deionized water with a volume ratio of tetrahydrofuran to deionized water of 1:1-1:

2. Stir at room temperature for 1-5 hours. After dialysis for 12-24 hours, freeze-drying is performed to obtain a yellow solid composite material (Eu4L4)(phen)4@F127. The synthesis route is shown in the following formula: 。 3. Use of the composite material containing the rare earth organic tetrahedral molecular cage complex structure prepared according to claim 2 as a carrier for preparing inner ear drugs.

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