Myricetin-loaded bone-targeted magnetic composite nano-microsphere as well as preparation method and application thereof
By preparing bone-targeted magnetic composite nanospheres loaded with myricetin, the deficiencies of imaging examinations and drug treatments in existing technologies are solved, and the effects of early diagnosis and targeted treatment of periprosthetic bone dissolution are achieved.
Patent Information
- Application Number
- CN202510990028.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-17
- Publication Date
- 2025-10-17
AI Technical Summary
The existing technology lacks a method for simultaneously performing imaging examinations and drug treatments for early diagnosis of periprosthetic osteolysis and targeted drug delivery to inhibit osteolysis.
Bone-targeted magnetic composite nanospheres loaded with myricetin were designed. Nanoparticles with ferroferric oxide as the core were prepared, loaded with myricetin after surface modification, and blocked with ketalthiocyanate-polyethylene glycol-aspartic acid hexapeptide molecules to form bone-targeted magnetic composite nanospheres.
It achieves early diagnosis of periprosthetic bone dissolution and targeted delivery of myricetin, which restores bone balance by inhibiting the release of osteoclasts and inflammatory factors, thereby preventing the occurrence and development of bone dissolution.
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Figure CN120789292A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to a kind of myricetin's bone targeting magnetic composite nanometer microspheres and its preparation method, and in bone lysis image tracing and the application in therapeutic drug. BACKGROUND
[0002] Artificial joint replacement has become one of the basic means for treating severe joint disease. However, the periprosthetic osteolysis caused by wear particles after the wear of the prosthesis interface is the main reason for the failure of artificial joints. We plan to diagnose early in the early stage of periprosthetic osteolysis (PO) through certain imaging methods; and target the drug myricetin to the surface of osteolysis, and restore bone balance through the bidirectional control of inhibiting osteoclasts and releasing inflammatory factors, so as to have the opportunity to kill the development of osteolysis in the cradle.
[0003] Therefore, it is very necessary to design a substance that can facilitate imaging examination and also has drug treatment effect. SUMMARY
[0004] The present application is designed to overcome the defects in the prior art by designing and constructing a substance with the architecture of bone targeting (TB) / loaded myricetin (LM) / magnetic nanometer microspheres.
[0005] The present application discloses a preparation method of bone targeting magnetic composite nanometer microspheres loaded with myricetin, comprising the following steps: Step 1: preparing nanoparticles with iron tetroxide (Fe3O4) as the core; Step 2: preparing magnetic mesoporous silica nanoparticles with iron tetroxide as the core according to the nanoparticles prepared in step 1; Step 3: performing amino modification treatment on the surface of the magnetic mesoporous silica nanoparticles prepared in step 2 to obtain modified magnetic mesoporous silica nanoparticles; Step 4: preparing ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecules (TK-PEG-ASP6); Step 5: loading myricetin on the modified magnetic mesoporous silica nanoparticles prepared in step 3, and then blocking the myricetin with the ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecules prepared in step 4 to obtain bone targeting magnetic composite nanometer microspheres loaded with myricetin.
[0006] Preferably, the specific steps of step 1 are: using iron perchlorate as the source of iron element, and preparing nanoparticles with iron tetroxide as the core by sol-gel method (Sol-Gel method).
[0007] Preferably, the step 2 specifically comprises the following steps: Step 2.1: The nanoparticles prepared in step 1 are added to a solvent, and the nanoparticles are uniformly dispersed in the solvent under ultrasonic; then a mesopore inducer is added, and the mesopore inducer is fully adsorbed on the surface of the nanoparticles under ultrasonic, and a mixed solution is obtained after stopping the ultrasonic; Step 2.2: The catalyst is slowly added dropwise to the mixed solution prepared in step 2.1 under stirring, and the pH value of the mixed solution is adjusted to 9-11, to obtain a reaction solution; Step 2.3: Tetraethyl orthosilicate is added dropwise to the reaction solution prepared in step 2.2, and after the dropwise addition is completed, the stirring reaction is continued at 30-50°C for 12-24 hours, and a crude product is obtained after the reaction is completed; Step 2.4: The crude product prepared in step 2.3 is subjected to solid-liquid separation by a magnet, and the liquid part after separation is discarded, to obtain a solid crude product; Step 2.5: The solid crude product prepared in step 2.4 is washed with anhydrous ethanol and deionized water respectively, and after each washing, the solid-liquid separation is performed by a magnet, and the liquid part after separation is discarded; the washed solid crude product is added to a hydrochloric acid-ethanol extraction liquid, and stirring extraction is performed at 60-80°C for 6-12 hours, and after the extraction is completed, the solid-liquid separation is performed by a magnet, and the liquid part after separation is discarded; the solid crude product is washed with anhydrous ethanol and deionized water respectively, and after each washing, the solid-liquid separation is performed by a magnet, and the liquid part after separation is discarded; finally, the solid crude product is dried by baking, to obtain the magnetic mesoporous silica nanoparticles with the ferroferric oxide as the inner core.
[0008] Preferably, the step 3 specifically comprises the following steps: Step 3.1: The magnetic mesoporous silica nanoparticles prepared in step 2 are dispersed in a solvent under ultrasonic, and then (3-aminopropyl) triethoxysilane (APTES) is added, and reflux reaction is performed under inert gas protection, so that the (3-aminopropyl) triethoxysilane reacts with the silicon hydroxyl on the surface of the magnetic mesoporous silica nanoparticles, and a crude product is obtained after the reaction is completed; Step 3.2: The crude product prepared in step 3.1 is subjected to solid-liquid separation by a magnet, and the liquid part is discarded; the remaining solid part is washed with anhydrous toluene and anhydrous ethanol respectively, and after each washing, the solid-liquid separation is performed by a magnet, and the liquid part after separation is discarded; the washed crude product is dried by baking, to obtain the magnetic mesoporous silica modified nanoparticles.
[0009] Preferably, the step 4 specifically comprises the following steps: Step 4.1: drop the ketone thioacetal (TK) dissolved in anhydrous dimethyl sulfoxide (DMSO) into the activated amino carboxyl polyethylene glycol (NH2-PEG-COOH) solution, and continue stirring at room temperature for 12-24 hours after dropping; after the reaction is completed, drop the reaction solution into ether to precipitate the product, collect the product by centrifugal separation, wash with ether, and dry in vacuum after washing to obtain ketone thioacetal-carboxyl polyethylene glycol molecules (TK-PEG-COOH); Step 4.2: dissolve the ketone thioacetal-carboxyl polyethylene glycol molecules prepared in step 4.1 in anhydrous dimethyl sulfoxide, and sequentially add 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl) and N-hydroxysuccinimide (NHS) to activate the carboxyl group; slowly drop the aspartic acid hexapeptide (ASP6) dissolved in anhydrous dimethyl sulfoxide into the activated reaction solution, and continue stirring at room temperature for 12-24 hours after dropping; Step 4.3: after the reaction in step 4.2 is completed, drop the reaction solution into ether to precipitate the product, collect the precipitate by centrifugal separation, wash the precipitate with ether, and dry the washed precipitate in vacuum to obtain a crude product; Step 4.4: purify the crude product prepared in step 4.3 by column chromatography or HPLC to obtain ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecules (TK-PEG-ASP6).
[0010] Preferably, the step 5 is specifically: dissolve myricetin in ethanol, then add the magnetic mesoporous silica modified nanoparticles prepared in step 3, stir and dissolve, then load by vacuum adsorption, and block the myricetin by using the ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecules prepared in step 4, freeze dry to remove ethanol after loading, to obtain the myricetin-loaded bone-targeting magnetic composite nanomicrospheres.
[0011] The application also discloses application of the myricetin-loaded bone-targeting magnetic composite nanomicrospheres in imaging tracing of osteolysis.
[0012] The application also discloses application of the myricetin-loaded bone-targeting magnetic composite nanomicrospheres in treating osteolysis.
[0013] Compared with the prior art, the application has the beneficial effects that: In the early stage of the occurrence of the bone resorption (PO) around the bone joint prosthesis, the early diagnosis can be carried out by the myricetin-loaded bone-targeting magnetic composite nanomicrospheres of the application combined with certain imaging methods; and the drug myricetin is targeted to the bone resorption surface, and the bone balance is restored through the bidirectional regulation of inhibiting osteoclasts and releasing inflammatory factors, so that the occurrence and development of bone resorption can be killed in the cradle. BRIEF DESCRIPTION OF DRAWINGS
[0014] Figure 1 It is a scanning electron microscope (SEM) schematic diagram of the myricetin-loaded bone-targeting magnetic composite nanomicrospheres; Figure 2 It is a scanning transmission electron microscope (STEM) schematic diagram of the myricetin-loaded bone-targeting magnetic composite nanomicrospheres; Figure 3 It is a transmission electron microscope (TEM) schematic diagram of the myricetin-loaded bone-targeting magnetic composite nanomicrospheres; Figure 4 It is a myricetin release curve schematic diagram of the nanomicrospheres; Figure 5 It is a nanomicrosphere bone targeting test result schematic diagram connected with ASP6; Figure 6 It is a nanomicrosphere bone targeting test result schematic diagram not connected with ASP6. DETAILED DESCRIPTION
[0015] In order to make the technical concept and advantages of the present application to realize the purpose of the application more clear and explicit, the technical solutions of the present application are further described in detail below in combination with the drawings. It should be understood that the following examples are only used to explain and illustrate the preferred embodiments of the present application, and should not be regarded as and constitute a limitation on the scope of the patent protection required by the present application. Example 1
[0016] The present embodiment discloses a preparation method of the myricetin-loaded bone-targeting magnetic composite nanomicrospheres, which comprises the following steps.
[0017] Step 1: preparing the nanometer particles with the iron tetroxide (Fe3O4) as the core, and the specific steps are as follows: The iron perchlorate is used as the source of iron element, and the nanometer particles with the iron tetroxide as the core are prepared by using the sol-gel method (Sol-Gel method).
[0018] The nanometer particles prepared by step 1 have magnetism, and the application of the nanometer particles can be used for diagnosis through MRI examination in the early stage of disease development.
[0019] Step 2: preparing the magnetic mesoporous silica nanometer particles with the iron tetroxide as the core according to the nanometer particles prepared in step 1; This step prepares magnetic mesoporous silica nanoparticles (MSN) with ferroferric oxide as the inner core, specifically including the following steps: Reagent preparation: tetraethyl orthosilicate (TEOS) is used as the silicon source, poloxamer 188 {Kolliphor® P 188 micro; trade name: Pluronic} is used as the mesoporous pore former, and anhydrous ethanol and deionized water are used as solvents, and an appropriate amount of ammonia water is prepared as a catalyst; Step 2.1: self-assembly reaction.
[0020] The nanoparticles prepared in step 1 are dispersed in a solvent composed of anhydrous ethanol and deionized water (the volume ratio of ethanol to deionized water is 3:1 to 4:1), and ultrasonic dispersion is performed for 30 minutes to 60 minutes to uniformly disperse the nanoparticles in the solvent; then, the mesoporous pore former is added, and ultrasonic dispersion is continued for 15 minutes to 30 minutes to allow the mesoporous pore former to be fully adsorbed on the surface of the nanoparticles; Step 2.2: slowly add the catalyst ammonia water under stirring to adjust the pH of the reaction solution to 9-11; Step 2.3: then add the tetraethyl orthosilicate dropwise, controlling the dropwise addition speed to be 1 drop / s to 2 drops / s; after the dropwise addition is completed, continue stirring at 30°C-50°C for 12 hours to 24 hours to allow the tetraethyl orthosilicate to hydrolyze and condense, forming a mesoporous silica coating layer on the surface of the nanoparticles; Step 2.4: after the reaction of step 2.3 is completed, the product is subjected to solid-liquid separation using a magnet, and the supernatant is discarded to obtain a solid crude product; Step 2.5: then wash the solid crude product with anhydrous ethanol and deionized water for 3 to 5 times, respectively, and after each washing, perform solid-liquid separation using a magnet and discard the washing liquid to remove unreacted reagents and impurities through the washing liquid; Prepare a hydrochloric acid-ethanol extraction solution by uniformly mixing concentrated hydrochloric acid and anhydrous ethanol in a volume ratio of 1:10-1:20; add the aforementioned washed solid to the prepared hydrochloric acid-ethanol extraction solution, and stir and extract at 60°C-80°C for 6 hours to 12 hours to allow the mesoporous pore former to be dissolved out of the mesoporous structure; After the extraction is completed, perform solid-liquid separation using a magnet, and discard the liquid part after separation; the obtained solid part is then washed with anhydrous ethanol and deionized water for 3 to 5 times, respectively, to remove residual extraction solution and dissolved pore former; Finally, dry the washed solid at 60°C-80°C for 6 hours to 12 hours to obtain magnetic mesoporous silica nanoparticles with ferroferric oxide as the inner core.
[0021] The magnetic mesoporous silica nanoparticles prepared in step 2 can be used as a carrier to load sustained-release drugs and other required functions.
[0022] Step 3: The surface of the magnetic mesoporous silica nanoparticles prepared in step 2 is subjected to an amination modification treatment to obtain magnetic mesoporous silica modified nanoparticles; the specific steps include the following steps: Reagent preparation: (3-Aminopropyl) triethoxysilane (APTES) is prepared as an amination reagent, and anhydrous toluene is prepared as a solvent.
[0023] Step 3.1: The magnetic mesoporous silica nanoparticles with magnetite as the core after drying in step 2 are dispersed in anhydrous toluene and ultrasonically dispersed for 30 minutes to 60 minutes; then, (3-aminopropyl) triethoxysilane is added, and the mass ratio of the magnetic mesoporous silica nanoparticles with magnetite as the core to (3-aminopropyl) triethoxysilane is 10:1 to 20:1, and the reaction is carried out under reflux at 80°C to 120°C for 12 hours to 24 hours under nitrogen protection, so that (3-aminopropyl) triethoxysilane reacts with the silicon hydroxyl on the surface of the mesoporous silica to achieve the amination modification of the surface of the nanoparticles.
[0024] Step 3.2: After the reaction is completed, the product is subjected to solid-liquid separation with a magnet, and is washed with anhydrous toluene and anhydrous ethanol for 3 to 5 times, respectively, to remove unreacted (3-aminopropyl) triethoxysilane and impurities. Finally, the amination modified nanoparticles are dried at 60°C-80°C for 6 hours to 12 hours to obtain magnetic mesoporous silica modified nanoparticles.
[0025] The dispersion of the magnetic mesoporous silica modified nanoparticles obtained in step 3 is significantly improved, the reaction activity, biocompatibility and functionalization ability are improved, and the application range is expanded.
[0026] Step 4: Preparation of ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecules (TK-PEG-ASP6), the specific steps are as follows: Step 4.1: The ketone thioacetal (TK) dissolved in anhydrous DMSO is slowly added dropwise to the activated amino carboxyl polyethylene glycol (NH2-PEG-COOH) solution under ice bath condition, the dropping speed is controlled at 1 drop / s to 2 drops / s; after the addition is completed, the ice bath is removed and the reaction is continued to stir at room temperature for 12 to 24 hours to allow the condensation reaction between the amino group and the activated carboxyl group to form an amide bond; after the reaction is completed, the reaction solution is slowly added dropwise into a large amount of cold ether to precipitate the product; the precipitate is collected by centrifugal separation and washed with cold ether for several times to remove the unreacted reagents and byproducts; the precipitate is vacuum dried to obtain the ketone thioacetal-carboxyl polyethylene glycol molecule (HOOC-PEG-TK).
[0027] Step 4.2: The ketone thioacetal-carboxyl polyethylene glycol molecule prepared in step 4.1 is dissolved in anhydrous DMSO in a dry round-bottom flask; under ice bath condition, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl) and N-hydroxysuccinimide (NHS) are sequentially added and stirred for 15 to 30 minutes to activate the carboxyl group. The aspartic acid hexapeptide (ASP6) previously dissolved in anhydrous DMSO is slowly added dropwise to the activated reaction solution, the dropping speed is controlled at 1 drop / s to 2 drops / s; after the addition is completed, the ice bath is removed and the reaction is continued to stir at room temperature for 12 to 24 hours to allow the condensation reaction between the amino group on the aspartic acid hexapeptide (ASP6) and the activated carboxyl group to form the ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecule (TK-PEG-ASP6 molecule).
[0028] Step 4.3: After the reaction in step 4.2 is completed, the reaction solution is slowly added dropwise into a large amount of cold ether to precipitate the product; the precipitate is collected by centrifugal separation and washed with cold ether for several times to remove the unreacted reagents and byproducts; the precipitate is vacuum dried to obtain the crude ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecule (TK-PEG-ASP6 molecule).
[0029] Step 4.4: The crude product is further purified by column chromatography or HPLC to obtain the purified ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecule (TK-PEG-ASP6 molecule).
[0030] Step 5: Myricetin was loaded on the magnetic mesoporous silica modified nanoparticles prepared in step 3, and after loading, the myricetin was blocked by the ketone thioacetal-polyethylene glycol-aspartic acid hexapeptide molecule prepared in step 4. The specific steps are as follows: myricetin was loaded by vacuum adsorption: myricetin was dissolved in ethanol and then added to the modified nanoparticles obtained in step 3 for stirring, and then vacuum was used for loading myricetin. Myricetin was blocked by the H2O2 sensitive material (TK-PEG-ASP6). After loading, ethanol was removed by freeze-drying to obtain bone-targeting magnetic composite nanomicrospheres loaded with myricetin.
[0031] Figure 1 A scanning electron microscope (SEM) schematic diagram of the bone-targeting magnetic composite nanomicrospheres loaded with myricetin.
[0032] Figure 2 A scanning transmission electron microscope (STEM) schematic diagram of the bone-targeting magnetic composite nanomicrospheres loaded with myricetin.
[0033] Figure 3 A transmission electron microscope (TEM) schematic diagram of the bone-targeting magnetic composite nanomicrospheres loaded with myricetin. Example Two
[0034] This example is a characterization analysis of the bone-targeting magnetic composite nanomicrospheres loaded with myricetin prepared in Example One.
[0035] 1. The particle size distribution was detected by SEM method (1) The treated nanomicrospheres were flushed with sterile PBS.
[0036] (2) The particles were fixed at 4°C for 2 hours using an electron microscope fixing solution (2.5% glutaraldehyde).
[0037] (3) The particles were repeatedly flushed with PBS pre-cooled to 4°C.
[0038] (4) The particles were fixed at 4°C for 2 hours using a 1% osmium acid / PBS fixing solution.
[0039] (5) Step (3) was repeated.
[0040] (6) The particles were gradient dehydrated using 30%, 50%, 70%, 80%, 90%, 95%, 100%, and 100% ethanol, respectively, for 10 minutes each, and then dehydrated using isoamyl acetate for 10 minutes twice.
[0041] (7) CO2 critical point drying and gold spraying.
[0042] (8) SEM observation.
[0043] The results are shown in Table 1. Figure 1 Table 1
[0044] 2. Using H2O2 to simulate the ROS in inflammatory environment to stimulate the drug release The loading amount of myricetin was detected by HPLC, and H2O2 was used to simulate the ROS in inflammatory environment to stimulate the drug release. It was shown that the nano-microspheres could slowly release myricetin in a certain acidic environment, which was described in detail in Figure 4 .
[0045] 3. Using hydroxyapatite (HA) to verify the targeting property of the nano-particles in vitro
[0046] The targeting property of the nano-particles was verified in vitro by using hydroxyapatite (HA). The results showed that the bone-targeting myricetin sustained-release nano-microspheres had good bone targeting property, which was described in detail in Figure 5 and Figure 6 .
[0047] It can be concluded from the above characterization and detection that the bone-targeting magnetic composite nano-microspheres loaded with myricetin were successfully prepared by the preparation method of Example 1, and exhibited good drug release performance and bone targeting performance in the characterization and detection.
[0048] Of course, the above only describes the preferred embodiments of the present application, and does not constitute a limitation on the present application. Those skilled in the art can modify the implementation of the present application without creative labor under the guidance of the prior art, and any modification or simple replacement or equivalent replacement made by using the conventional technical means in the art within the spirit and principles of the present application shall be included in the protection scope of the present application.
Claims
1. A method for preparing bone-targeted magnetic composite nanoparticles loaded with myricetin, characterized in that: The steps include: Step 1: preparing nanoparticles with ferroferric oxide as the core; Step 2: preparing magnetic mesoporous silica nanoparticles with ferroferric oxide as the core according to the nanoparticles prepared in step 1; Step 3: performing an amino modification treatment on the surface of the magnetic mesoporous silica nanoparticles prepared in step 2 to obtain magnetic mesoporous silica modified nanoparticles; Step 4: preparing ketal-polyethylene glycol-aspartic acid hexapeptide molecules; Step 5: Load myricetin onto the magnetic mesoporous silica-modified nanoparticles prepared in step 3. After loading, block the myricetin with the thioketal-polyethylene glycol-aspartic acid hexapeptide molecules prepared in step 4 to obtain bone-targeted magnetic composite nanospheres loaded with myricetin.
2. The method for preparing bone-targeted magnetic composite nanoparticles loaded with myricetin according to claim 1, characterized in that: The specific steps of step 1 are: using ferric perchlorate as the source of iron element and adopting the sol-gel method to prepare nanoparticles with ferrosoferric oxide as the core.
3. The method for preparing myricetin-loaded bone-targeted magnetic composite nanoparticles according to claim 1, wherein: The step 2 specifically includes the following steps: Step 2.1: Add the nanoparticles prepared in step 1 to a solvent and uniformly disperse the nanoparticles in the solvent under ultrasound; then add a mesoporous porogen and continue ultrasound to allow the mesoporous porogen to fully adsorb on the surface of the nanoparticles. After stopping ultrasound, a mixed solution is obtained; Step 2.2: Slowly adding a catalyst dropwise to the mixed solution prepared in step 2.1 under stirring, and adjusting the pH value of the mixed solution to 9-11 to obtain a reaction solution; Step 2.3: Add ethyl orthosilicate dropwise to the reaction solution prepared in step 2.
2. After the addition is complete, continue stirring and reacting at 30°C-50°C for 12 to 24 hours. After the reaction is complete, a crude product is obtained. Step 2.4: Using a magnet to separate the crude product obtained in step 2.3 into liquid, discard the separated liquid portion to obtain a crude solid product; Step 2.5: The crude solid product prepared in step 2.4 is washed with anhydrous ethanol and deionized water, respectively, and after each washing, a magnet is used to separate the solid and liquid, and the separated liquid portion is discarded; the washed crude solid product is added to a hydrochloric acid-ethanol extract, and stirred and extracted at 60°C-80°C for 6 to 12 hours. After the extraction, a magnet is used to separate the solid and liquid, and the separated liquid portion is discarded. The crude solid product is then washed with anhydrous ethanol and deionized water, respectively, and after each washing, a magnet is used to separate the solid and liquid, and the separated liquid portion is discarded; finally, the crude solid product is dried to obtain magnetic mesoporous silica nanoparticles with ferrosoferric oxide as the core.
4. The method for preparing myricetin-loaded bone-targeted magnetic composite nanoparticles according to claim 1, wherein: The step 3 specifically includes the following steps: Step 3.1: The magnetic mesoporous silica nanoparticles prepared in Step 2 are dispersed in a solvent under ultrasound, and then (3-aminopropyl)triethoxysilane is added. The mixture is refluxed under inert gas protection to allow the (3-aminopropyl)triethoxysilane to react with the silanol groups on the surface of the magnetic mesoporous silica nanoparticles. After the reaction is completed, a crude product is obtained. Step 3.2: The crude product prepared in step 3.1 is subjected to solid-liquid separation using a magnet, the liquid portion is discarded, and the remaining solid portion is washed with anhydrous toluene and anhydrous ethanol, respectively. After each washing, the solid-liquid separation is performed using a magnet, and the separated liquid portion is discarded; the washed crude product is dried to obtain magnetic mesoporous silica-modified nanoparticles.
5. The method for preparing myricetin-loaded bone-targeted magnetic composite nanoparticles according to claim 1, wherein: The step 4 specifically includes the following steps: Step 4.1: Add thioketal dissolved in anhydrous dimethyl sulfoxide dropwise to the activated aminocarboxyl polyethylene glycol solution. After the addition is complete, continue stirring and react at room temperature for 12 to 24 hours. After the reaction is complete, add the reaction solution dropwise to diethyl ether to precipitate the product. The product is collected by centrifugation, washed with diethyl ether, and then dried under vacuum to obtain the thioketal-carboxyl polyethylene glycol molecule. Step 4.2: Dissolve the thioketal-carboxyl polyethylene glycol molecule prepared in step 4.1 in anhydrous dimethyl sulfoxide, add ethyldimethylaminopropylcarbodiimide hydrochloride and N-hydroxysuccinimide in sequence, and stir to react to activate the carboxyl group; slowly add the aspartic acid hexapeptide dissolved in anhydrous dimethyl sulfoxide dropwise to the activated reaction solution. After the addition is complete, continue stirring at room temperature for 12 to 24 hours. Step 4.3: After the reaction in step 4.2 is completed, the reaction solution is added dropwise to diethyl ether to precipitate the product. The precipitate is collected by centrifugation, washed with diethyl ether, and vacuum dried to obtain a crude product. Step 4.4: The crude product prepared in step 4.3 is purified by column chromatography or HPLC to obtain a thioketal-polyethylene glycol-aspartic acid hexapeptide molecule.
6. The method for preparing myricetin-loaded bone-targeted magnetic composite nanoparticles according to claim 1, characterized in that: The specific steps of step 5 are: dissolving myricetin in ethanol and then adding the magnetic mesoporous silica modified nanoparticles prepared in step 3, stirring to dissolve, then loading by vacuum adsorption, and using the ketalthioal-polyethylene glycol-aspartic acid hexapeptide molecules prepared in step 4 to block the myricetin, and after loading, freeze-drying to remove ethanol to obtain bone-targeted magnetic composite nanospheres loaded with myricetin.
7. The preparation method according to any one of claims 1 to 6 to prepare bone-targeted magnetic composite nanospheres loaded with myricetin.
8. Use of the myricetin-loaded bone-targeted magnetic composite nanoparticles according to claim 7 in imaging tracing of osteolysis.
9. Use of the myricetin-loaded bone-targeted magnetic composite nanoparticles according to claim 7 in a drug for treating osteolysis.