Preparation method and application of functional hydrotalcite medicinal nanoparticles

Abstract

The invention discloses a preparation method and application of functionalized hydrotalcite medicinal nano-particles, hydrotalcite nano-particles are reassembled by introducing metal ions with different valence states, so that a hydrotalcite laminate has permanent positive charges and has good biocompatibility and electrostatic adsorption capacity; rNA family molecules with negative charges are adsorbed to the surfaces of the particles through the electrostatic adsorption effect, the functionalized hydrotalcite medicinal nanoparticles with good stability are obtained, the drug loading capacity is improved, effective loading and continuous release of drugs are achieved, and more channels can be provided for precise delivery of therapeutic drugs. According to the present invention, the application is used for treating the intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, can effectively treat the intervertebral disc degeneration, and can fundamentally efficiently repair the degenerated intervertebral disc under the condition of no side effect so as to achieve the effect of relieving the intervertebral disc-derived pain.

Description

TECHNICAL FIELD

[0001] The present application relates to a preparation method of functionalized hydrotalcite medicinal nanoparticles and its use, belonging to the technical field of biological therapy. BACKGROUND

[0002] Intervertebral disc is the largest avascular tissue in mammals. NPCs exhibit a unique metabolic characteristic of glycolysis due to the avascular and hypoxic microenvironment. Compared with cells that rely on oxidative metabolism, NPCs are generally considered to contain few functional mitochondria. This cognition has led to the long-standing misunderstanding of NPCs "metabolic simplification theory" in the academic field, causing the dynamic regulation role of NPCs mitochondria in cell homeostasis maintenance to be often ignored. In fact, mitochondrial autophagy is a key mechanism for cells to remove damaged or dysfunctional mitochondria through selective autophagy, which is crucial for maintaining cellular energy homeostasis, redox balance and survival.

[0003] Recent studies have shown that mitochondrial autophagy in degenerative NPCs presents an abnormal dynamic pattern of "compensatory activation - functional compensation disorder - blockage", which is essentially due to the self-sustaining vicious cycle of mitochondrial dysfunction and oxidative stress. In degenerative NPCs, mitochondrial electron transport chain dysfunction leads to a significant increase in ROS generation rate and intradiscal oxidative stress microenvironment. In the early stage of IVDD, mitochondrial autophagy is compensatorily enhanced due to oxidative stress, but as the degeneration progresses, lysosomal acidification disorder and excessive activation of downstream inflammatory pathways lead to autophagic flow blockage, and undegraded mitochondrial fragments continuously release mitochondrial DNA (mtDNA) and trigger an inflammatory factor storm, ultimately forming a vicious cycle of "mitochondrial damage - ROS explosion - autophagy inhibition - inflammation cascade", accelerating extracellular matrix (ECM) degradation and loss of intervertebral disc mechanical function. The normal function of the intervertebral disc is highly dependent on the structural integrity of the ECM, and its degradation will lead to a decline in mechanical properties and an exacerbation of inflammatory reactions, ultimately triggering degeneration. Intervertebral disc degeneration and the resulting low back pain have become one of the main sources of global disease burden, severely affecting patients' quality of life. It is not only an individual health problem, but also a global public health challenge. Current surgical reconstruction therapy mainly based on spinal fusion is still the mainstream strategy for treating low back pain. However, spinal fusion surgery can provide short-term relief, but it has limitations that cannot be ignored: first, the accelerated degeneration of adjacent segments caused by surgical trauma forms a vicious cycle of "treatment - damage - treatment"; second, surgery cannot reverse the core pathological processes of intervertebral disc extracellular matrix degradation and nucleus pulposus cell (NPC) aging, only achieving mechanical stability rather than biological repair.

[0004] This palliative treatment at the expense of dynamic function of the spine highlights the urgency of developing new regenerative therapies targeting the molecular mechanisms of IVDD. In the prior art, nanomedicine, as an emerging technology, has shown great potential in drug delivery, tissue engineering, and cell therapy due to its unique physical and chemical properties at the nanoscale. Among them, the adjustable layer chemical composition, interlayer anion type and quantity, and excellent ion exchange performance and thermal stability of hydrotalcite nanoparticles make them have broad application prospects in catalysis, flame retardant, thermal stability, adsorption separation, and biological medicine. Therefore, it is necessary to propose a preparation method and use of functionalized hydrotalcite medicinal nanoparticles based on the unique properties of metal ions to improve biocompatibility, antioxidant properties, and treatment effect on potential intervertebral disc degeneration, prolong the effect of drug action, and selectively activate mitochondrial autophagy, which is suitable for signal-dependent or drug dose-dependent regulation. SUMMARY

[0005] The purpose of the present application is to solve the above problems and provide a preparation method and use of functionalized hydrotalcite medicinal nanoparticles to overcome the problem of intervertebral disc cell damage, destruction of extracellular matrix, and ultimately damage to the intervertebral disc structure caused by intervertebral disc degeneration.

[0006] The technical solution of the present application is: a preparation method of functionalized hydrotalcite medicinal nanoparticles, comprising the following steps:

[0007] Step (one) at least one divalent metal ion compound is used as the first synthesis of the functionalized hydrotalcite medicinal nanoparticles. The divalent metal ion compound is prepared by co-precipitation of aluminum nitrate and divalent metal ion compound (optimizing the batch consistency of co-precipitation method to ensure the monodispersity of nanoparticles). The molar mass of the divalent metal ion compound and the aluminum nitrate is 2:1. Under the action of an electric rotating device, aluminum nitrate and divalent metal ion compound are added at the same time. After overnight shaking on a shaker and centrifugal separation to remove the residue, divalent metal ion compound hydrotalcite nanoparticle precipitate is prepared. Pure water is added to the divalent metal ion compound hydrotalcite nanoparticle precipitate and the product is uniformly washed by ultrasonic mixing. The precipitate after centrifugal treatment is the divalent metal ion compound hydrotalcite nanoparticle. Finally, the hydrotalcite nanoparticles are fully dissolved in an organic solvent (such as dimethyl sulfoxide) to obtain a divalent metal ion compound hydrotalcite nanoparticle aqueous solution.

[0008] Step (two) the second synthesis of the functionalized hydrotalcite pharmaceutical nanoparticles with the drug-loaded prepared by using the negatively charged RNA family, under the action of ultrasonic, to the bivalent metal ion compound of the hydrotalcite nanoparticles aqueous solution prepared in step S1, 10-20%wt of the negatively charged RNA family is added, after fully mixing, the organic solvent (for example: dimethyl sulfoxide) in the mixture is fully evaporated by the electric rotation heating equipment, then ultrapure water is added to redissolve the hydrotalcite nanoparticles, the unbound negatively charged RNA family is removed by centrifugal separation, and the functionalized hydrotalcite pharmaceutical nanoparticles are obtained.

[0009] Further, the above-mentioned preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles, wherein: during the operation of the coprecipitation method: the overall pH value is controlled to be between 10-10.5 by dropwise adding sodium hydroxide.

[0010] Further, the above-mentioned preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles, wherein: the bivalent metal ion compound includes but is not limited to zinc nitrate, cobalt nitrate.

[0011] Further, the above-mentioned preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles, wherein: the negatively charged RNA family includes but is not limited to siRNA, shRNA.

[0012] Further, the above-mentioned preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles, wherein: the frequency of the ultrasonic wave is 20-40 kHz.

[0013] Further, the above-mentioned preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles, wherein: the mixing time of the bivalent metal ion compound of the hydrotalcite nanoparticles aqueous solution and the negatively charged RNA family is 0.5-1.5 h.

[0014] Further, the above-mentioned preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles, wherein: the centrifugal treatment of the hydrotalcite nanoparticles precipitate of the negatively charged RNA family is repeated at least three times, and the corresponding centrifugal speed is set to 8000 rpm and the time is set to 5 min each time.

[0015] Use of the functionalized hydrotalcite medicinal nanoparticles prepared by the above preparation method: the functionalized hydrotalcite medicinal nanoparticles are positively charged metal hydroxide layers and interlayer exchangeable anion reaction synthesis, which are used for preparing a drug for treating intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, so as to treat the intervertebral disc degeneration, wherein the intervertebral disc degeneration is intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, the degenerative intervertebral disc is fundamentally repaired without side effects, and the effect of relieving intervertebral disc pain is achieved, and the functionalized hydrotalcite medicinal nanoparticles have the following characteristics: the functionalized hydrotalcite medicinal nanoparticles can be directly dispersed in physiological saline or buffer to form a stable suspension, and then the suspension can be injected into the central part (nucleus pulposus region) of the intervertebral disc through fine needle (22-25G) puncture under image guidance (X-ray or CT) with a dose of 50-100 μL (containing 1-5 mg / mL of functionalized hydrotalcite medicinal nanoparticles), and the injection is synchronized with minimally invasive surgery (such as intervertebral disc decompression), so that the repair effect is enhanced, and the nanometer size is easy to penetrate into the degenerative intervertebral disc tissue.

[0016] Further, the functionalized hydrotalcite medicinal nanoparticles can be used as a carrier of stem cells (for example: MSCs) and combined with cell therapy to enhance cell survival and differentiation; and can be combined with pulsed electromagnetic field (PEMF) to promote ion penetration and assist physical therapy.

[0017] By using the technical scheme of the present application, the aluminum hydrotalcite is modified by co-precipitation method using divalent metal salt and aluminum salt, the drug performance is improved by constructing multi-metal hydroxide, the whole carries positive charge at the same time, so as to have good biocompatibility and water solubility, and then the functionalized hydrotalcite medicinal nanoparticles with stable covalent bond are obtained by electrostatic adsorption of RNA family with negative charge. The functionalized hydrotalcite medicinal nanoparticles not only improve the stability and drug loading capacity, realize effective loading and sustained release of the drug, but also provide more possibilities for precise delivery of the therapeutic drug.

[0018] Compared with the prior art, the functionalized hydrotalcite medicinal nanoparticles are used for preparing the drug for treating intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, which can effectively treat the intervertebral disc degeneration, fundamentally repair the degenerative intervertebral disc without side effects, and relieve intervertebral disc pain.

[0019] In addition, the technical scheme of the present application can also be combined with other treatment methods, such as immunomodulators, biological agents, etc., to achieve better intervertebral disc recovery effect through synergistic treatment. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 It is a transmission electron microscope (TEM) imaging diagram of the functionalized hydrotalcite medicinal nanoparticles of the present application;

[0021] Figure 2 X-ray diffraction (XRD) image of the functionalized hydrotalcite pharmaceutical nanoparticles of the present application;

[0022] Figure 3 Trend comparative imaging of the intervertebral disc structure of the rats after the nuclear magnetic resonance (MRI) treatment of Comparative Examples 1-4 and Example 1 of the present application;

[0023] Figure 4 Trend comparative imaging of the collagen type II staining in the intervertebral disc tissue of Comparative Examples 1-4 and Example 1 of the present application using the immunofluorescence technique;

[0024] Figure 5 Trend comparative imaging of the metalloproteinase 3 staining in the intervertebral disc tissue of Comparative Examples 1-4 and Example 1 of the present application using the immunofluorescence technique;

[0025] Figure 6 Trend comparative imaging of the mitochondrial translocase 20 and microtubule-associated protein 1 light chain 3 staining in the intervertebral disc tissue of Comparative Examples 1-4 and Example 1 of the present application using the immunofluorescence technique;

[0026] Figure 7 Trend comparative imaging of the mitochondrial membrane potential staining in the intervertebral disc tissue of Comparative Examples 1-4 and Example 1 of the present application using the immunofluorescence technique. DETAILED DESCRIPTION

[0027] In order to make the objectives, technical solutions and advantages of the present application clearer, further description will be made to the present application in combination with specific examples, but it should not be understood that the protection scope of the above-mentioned subject matter of the present application is limited to the following examples. The rat caudal vertebrae needle puncture intervertebral disc degeneration model involved in the examples is a commonly used model generally recognized by those skilled in the art, and the present application has no special requirements therefor.

[0028] According to the technical solution of the present application, the preparation method of the functionalized hydrotalcite pharmaceutical nanoparticles used in Example 1 is as follows:

[0029] The hydrotalcite nanoparticles were prepared by coprecipitation method, and then the prepared hydrotalcite nanoparticles were fully dissolved in ultrapure water. Under the action of ultrasonic waves with a frequency of 30 kHz (i.e., the ultrasonic wave generation was alternately performed for three seconds and stopped for one second, which can effectively save energy, prolong the service life of the ultrasonic wave equipment, and improve the uniformity of material mixing, increase the particle dispersion, and accelerate the chemical reaction), 20%wt of short hairpin ribonucleic acid (shRNA) was added. The mixture was shaken overnight at 25°C, and centrifugation was performed at a speed of 70 rpm to remove the residual loaded drugs in the supernatant, to obtain the short hairpin ribonucleic acid (shRNA) loaded hydrotalcite nanoparticle precipitate. After resuspension with ultrapure water, centrifugation was performed at a speed of 8000 rpm for 5 minutes each time, and the impurities and unbound loaded drugs were washed away for three times. Finally, the supernatant was removed by centrifugation, to obtain the functionalized hydrotalcite pharmaceutical nanoparticles (CoAlZn-LDH@shSTING).

[0030] As shown in Figure 1 , the successful synthesis of the functionalized hydrotalcite pharmaceutical nanoparticles was confirmed by electron microscopy shooting; as shown in Figure 2 , the successful synthesis of the functionalized hydrotalcite pharmaceutical nanoparticles was confirmed by X-ray diffraction experiment (the functionalized hydrotalcite pharmaceutical nanoparticles have good crystallization and stable particles).

[0031] Example 1

[0032] A rat tail vertebra intervertebral disc degeneration model was constructed, and after the tail vertebra puncture, 2 μl of CoZnAl-LDH@shSTING was injected into the model. The injection was performed once a week, and the treatment was maintained for 4 weeks.

[0033] Comparative Example 1

[0034] A rat tail vertebra intervertebral disc degeneration model was constructed, and the tail vertebra puncture was not performed, and no drug intervention was performed, and the maintenance was maintained for 4 weeks.

[0035] Comparative Example 2

[0036] A rat tail vertebra intervertebral disc degeneration model was constructed, and the tail vertebra puncture was performed, and no drug intervention was performed, and the maintenance was maintained for 4 weeks.

[0037] Comparative Example 3

[0038] A rat tail vertebra intervertebral disc degeneration model was constructed, and after the tail vertebra puncture, 2 μl of CoZnAl-LDH was injected into the model. The injection was performed once a week, and the treatment was maintained for 4 weeks.

[0039] Comparative Example 4

[0040] A rat tail vertebrae needle disc degeneration model was constructed, and after tail vertebrae puncture, 2 μl of shSTING was injected thereinto; once a week for 4 weeks.

[0041] As shown in Figure 3 , the application effect was evaluated by imaging the intervertebral disc structure of the rats in Comparative Examples 1-4 and Example 1 by MRI (magnetic resonance imaging), to evaluate the morphological changes and degeneration degree of the intervertebral disc. In Comparative Examples 2-4, the MRI images showed a decrease in signal intensity, indicating that the intervertebral disc was dehydrated; compared with Comparative Example 2, the intervertebral disc morphology of each injection group in Comparative Example 3, Comparative Example 4 and Example 1 was recovered to varying degrees, and the intervertebral disc of Example 1 showed the strongest signal intensity, showing the best in vivo treatment effect.

[0042] As shown in Figure 4 and Figure 5 , the application effect was evaluated by fluorescence immunostaining, and the nucleus pulposus cells of Comparative Examples 1-4 and Example 1 were subjected to extracellular matrix (type II collagen, matrix metalloproteinase-3) staining and cytoskeleton (phalloidin) staining, to observe the cell morphology, matrix degradation and cell number changes of the nucleus pulposus cells in each group. Type II collagen positively promotes matrix synthesis, while matrix metalloproteinase 3 promotes matrix degradation. Among them, the type II collagen staining at two time points showed that the green fluorescence of Comparative Example 1 and Comparative Example 2 was significantly different, and the green fluorescence of Comparative Example 1 was significantly brighter than that of Comparative Example 2. In contrast, the green fluorescence intensity of Comparative Example 3 and Comparative Example 4 was similar, and was stronger than that of Comparative Example 2 and weaker than that of Comparative Example 1; the green fluorescence intensity of the nucleus pulposus cells of Example 1 was significantly stronger than that of Comparative Example 2, and was stronger than that of Comparative Example 3 and Comparative Example 4. Thus, it can be seen that Example 1 shows the best recovery effect of its nucleus pulposus cells in vivo treatment.

[0043] As shown in Figure 6 , the application effects of Comparative Examples 1-4 and Example 1 were also evaluated by fluorescence immunostaining, and the rat nucleus pulposus cells were subjected to fluorescence immunostaining to detect mitochondrial translocase 20 and microtubule-associated protein 1 light chain 3 in the intervertebral disc tissue, wherein mitochondrial translocase 20 is a marker for intervertebral disc mitochondrial autophagy, and microtubule-associated protein 1 light chain 3 is a recognized marker for cellular autophagy. Compared with Comparative Example 1, the co-localization area of Comparative Examples 2, 3 and 4 was reduced, but the co-localization area of Example 1 was close to that of Comparative Example 1; compared with Comparative Example 2, the co-localization area of Comparative Examples 3 and 4 was slightly larger, and the co-localization area of Example 1 was significantly better than that of Comparative Examples 3 and 4. Thus, it can be concluded that Example 1 shows the best recovery effect of its intervertebral disc tissue in vivo treatment.

[0044] As shown in Figure 7As shown, the application effects of Comparative Examples 1-4 and Example 1 were evaluated by fluorescence immunostaining, human nucleus pulposus cells were taken for fluorescence immunostaining, and the change of mitochondrial membrane potential in intervertebral disc tissue was detected, wherein JC-1 is a fluorescent probe commonly used for detecting the change of mitochondrial membrane potential. Healthy mitochondria emit red fluorescence, and unhealthy mitochondria emit green fluorescence. The green fluorescence of Comparative Example 1, Comparative Example 3, Comparative Example 4 and Example 1 was significantly lower than that of Comparative Example 2, and the green fluorescence intensity of Example 1 was the weakest under the condition of similar red fluorescence intensity. Therefore, Example 1 has strong ability to protect mitochondria, and shows that the recovery effect of intervertebral disc tissue in vivo treatment is best.

[0045] In summary, in the technical scheme of the present application, the functional hydrotalcite nanoparticles are used to prepare a drug for treating intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, which can effectively treat intervertebral disc degeneration and has significant treatment effect.

[0046] Therefore, by using the technical scheme of the present application, the bivalent metal salt and aluminum salt are used to modify aluminum hydrotalcite by coprecipitation method, the drug performance is improved by constructing a multi-metal hydroxide, at the same time the whole carries a positive charge, thereby having good biocompatibility and water solubility, and then the RNA family with negative charge is used for electrostatic adsorption, thereby obtaining functional hydrotalcite pharmaceutical nanoparticles with stable covalent bond. The functional hydrotalcite pharmaceutical nanoparticles not only improve the stability and drug loading capacity, realize effective loading and sustained release of the drug, but also provide more possibilities for precise delivery of therapeutic drugs.

[0047] As can be found from the above description, compared with the prior art, the functional hydrotalcite pharmaceutical nanoparticles are used to prepare a drug for treating intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, which can effectively treat intervertebral disc degeneration, fundamentally and gently repair the degenerated intervertebral disc without side effects, and achieve the effect of relieving intervertebral disc-derived pain. In addition, the technical scheme of the present application can also be combined with other treatment methods, such as immunomodulators, biological agents, etc., to synergistically treat and better restore intervertebral disc health.

[0048] The technical scheme, working process and implementation effect of the present application are described in detail above, and it should be noted that the described is only a typical example of the present application, in addition to which the present application can have other various specific implementation manners, and any technical scheme formed by equivalent substitution or equivalent transformation falls within the scope of protection of the present application.

Claims

1. A process for the preparation of functionalized hydrotalcite pharmaceutical nanoparticles characterized in that The method comprises the following steps: Step S1: using at least one divalent metal ion compound as the drug loaded in the first synthesis of the functionalized hydrotalcite pharmaceutical nanoparticles, the divalent metal ion compound hydrotalcite nanoparticles are prepared by the coprecipitation method of aluminum nitrate and divalent metal ion compound, wherein the molar mass of the divalent metal ion compound and the aluminum nitrate is 2:1, the divalent metal ion compound hydrotalcite nanoparticles are fully dissolved in an organic solvent to obtain a divalent metal ion compound hydrotalcite nanoparticle aqueous solution; Step S2: using a negatively charged RNA family as the drug loaded in the second synthesis of the functionalized hydrotalcite pharmaceutical nanoparticles, under the action of ultrasonic waves, 10-20% wt of the negatively charged RNA family is added to the divalent metal ion compound hydrotalcite nanoparticle aqueous solution prepared in step S1, after fully mixing, the organic solvent in the mixture is fully evaporated by an electric rotation heating device, then the negatively charged RNA family hydrotalcite nanoparticles are redissolved by adding ultrapure water, and the unbound negatively charged RNA family is removed by centrifugal separation to obtain the functionalized hydrotalcite pharmaceutical nanoparticles.

2. The process for the preparation of functionalized hydrotalcite pharmaceutical nanoparticles according to claim 1, characterized by the fact that: In step S1, the operation process of the coprecipitation method is that, under the action of an electric rotation device, the aluminum nitrate and the divalent metal ion compound are simultaneously added, after overnight shaking bed and centrifugal separation to remove the residues, the divalent metal ion compound hydrotalcite nanoparticle precipitate is prepared, then pure water is added to the divalent metal ion compound hydrotalcite nanoparticle precipitate to uniformly wash the product by ultrasonic mixing, and the precipitate after centrifugal treatment is the divalent metal ion compound hydrotalcite nanoparticles.

3. The method for preparing functionalized hydrotalcite pharmaceutical nanoparticles according to claim 2, characterized in that: In the operation process of the coprecipitation method, the overall pH value is controlled to be between 10-10.5 by dropwise adding sodium hydroxide.

4. The process for the preparation of functionalized hydrotalcite pharmaceutical nanoparticles according to claim 1, characterized in that: The divalent metal ion compound includes but is not limited to zinc nitrate and cobalt nitrate.

5. The method for preparing functionalized hydrotalcite pharmaceutical nanoparticles according to claim 1, characterized in that: The negatively charged RNA family includes but is not limited to siRNA and shRNA.

6. The method for preparing functionalized hydrotalcite pharmaceutical nanoparticles according to claim 1, characterized in that: In step S2, the frequency of the ultrasonic waves is 20-40 kHz.

7. The method for preparing functionalized hydrotalcite pharmaceutical nanoparticles according to claim 1, characterized in that: In step S2, the divalent metal ion compound hydrotalcite nanoparticle aqueous solution and the negatively charged RNA family are fully mixed for 0.5-1.5 h.

8. The method for preparing functionalized hydrotalcite pharmaceutical nanoparticles according to claim 1, characterized in that: In step S2, the centrifugal treatment of the negatively charged RNA family hydrotalcite nanoparticle precipitate is repeated at least three times, and the corresponding centrifugal speed is set to 8000 rpm and the time is set to 5 min each time.

9. Use of the functionalized hydrotalcite nanoparticle of any one of claims 1 to 8, said functionalized hydrotalcite nanoparticle being synthetized by reaction of a positively charged metal hydroxide layer and of an interlayer exchangeable anion, characterized in that: The functionalized hydrotalcite pharmaceutical nanoparticles are used for preparing a drug for treating intervertebral disc degeneration caused by mitochondrial autophagy disorder and oxidative stress, the functionalized hydrotalcite pharmaceutical nanoparticles can be directly dispersed in physiological saline or buffer to form a stable suspension, then under the guidance of imaging, the functionalized hydrotalcite pharmaceutical nanoparticles are injected into the center of the intervertebral disc through fine needle puncture at a dose of 50-100 μL, wherein the functionalized hydrotalcite pharmaceutical nanoparticles are 1-5 mg / mL, and the injection is performed synchronously with a minimally invasive surgery.

10. Use of the functionalized hydrotalcite pharmaceutical nanoparticle according to claim 9, characterized by the fact that: The functionalized hydrotalcite pharmaceutical nanoparticles are used as a carrier of stem cells and combined with cell therapy to enhance cell survival and differentiation, and can also be combined with a pulsed electromagnetic field to promote ion penetration and assist physical therapy.

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