A natural stibiconite microneedle for cancer treatment and a preparation method and application thereof

Abstract

The application discloses natural stibiconite microneedles for cancer treatment and a preparation method and application thereof. The preparation method comprises the following steps: after natural stibiconite is sequentially subjected to mechanical refinement and calcination activation, the stibiconite is uniformly stirred in deionized water together with a gelling agent to obtain a precursor solution, and then the precursor solution is injected into a microneedle mold to be solidified and formed, thereby obtaining the microneedles. The microneedles obtained by the above method utilize the unique crystal lattice structure and ion composition of the mineral, and act on tumor cells through multiple mechanisms, so that excellent tumor treatment effect can be achieved at a lower dosage. According to test, in 15 days of treatment, the tumor volume of mice in a microneedle administration group is 204.31±82.68 mm 3 , while the tumor volume of mice in a blank control group is as high as 1542.53±298.19 mm 3 , which shows excellent tumor inhibition.

Description

Technical Field

[0001] This invention relates to a microneedle for cancer treatment, specifically to a natural antimony chalcopyrite microneedle for cancer treatment, its preparation method, and its application, belonging to the field of pharmaceutical technology. Background Technology

[0002] Cancer is a major disease that seriously threatens human life and health. Current cancer treatment technologies have gradually evolved from the early treatment model primarily based on surgical resection, radiotherapy, and chemotherapy to a comprehensive intervention system that includes targeted therapy, immunotherapy, and various combination therapies. Although these treatments have played a significant role in prolonging patient survival, alleviating symptoms, and reducing the risk of recurrence in some cases, how to effectively kill tumor cells while minimizing damage to normal tissues remains a key, long-standing, unresolved issue in the field of cancer treatment.

[0003] In current technologies, chemotherapy drugs, radiosensitizers, immunomodulators, and other antitumor active ingredients mostly rely on systemic administration or conventional local injection to exert their effects. These administration methods are prone to non-specific drug distribution within the body, leading to significant systemic toxicity and adverse reactions. Furthermore, tumor tissues generally possess complex tumor microenvironments, including abnormal vascular structures, increased interstitial pressure, hypoxia, acidity, and immunosuppression, which limit the accumulation, penetration, and sustained action of drugs at the tumor site, thus affecting the actual therapeutic efficacy of chemotherapy, radiotherapy, and immunotherapy. In other words, although current tumor treatments are becoming increasingly diverse, precise delivery to the tumor site, efficient local accumulation, and controlled release remain significant bottlenecks restricting the improvement of efficacy.

[0004] To improve the targeting and controlled release capabilities of tumor therapy, various artificially constructed delivery systems have been developed in recent years, such as liposomes, polymer nanoparticles, inorganic nanomaterials, and stimulus-responsive carriers. These technologies have shown potential in improving drug stability, enhancing pharmacokinetic behavior, and improving tumor site delivery, thus becoming an important research direction in the field of tumor delivery. However, existing artificial carriers and nanoplatforms still face several prominent challenges in their clinical translation, such as complex material composition and preparation processes, difficulties in batch consistency and large-scale preparation, unclear in vivo metabolic fate and long-term safety, and the potential for additional biological risks arising from interactions between materials and the body's proteins, lipids, and immune system. These issues, to some extent, limit the application prospects and industrialization of these technologies.

[0005] Meanwhile, microneedle delivery technology, as a rapidly developing local drug delivery method in recent years, has shown application potential in percutaneous drug delivery and superficial lesion treatment due to its ability to overcome the stratum corneum barrier, minimally invasive nature, local drug delivery, and reduced systemic exposure. It is particularly considered suitable for superficial tumors or postoperative local interventions. Nevertheless, existing microneedle technology itself still has room for improvement. For example, current microneedles mostly rely on materials such as silicon, metals, or polymers for preparation and typically require additional loading of chemotherapeutic drugs, photosensitizers, nucleic acid drugs, or immune molecules. Their mechanical strength, drug loading capacity, drug release behavior, biocompatibility, manufacturing cost, large-scale preparation, and quality control still need to be balanced and optimized. Therefore, how to construct an anti-tumor microneedle system that combines material suitability, local delivery capability, fabrication feasibility, and translational potential remains an unsolved technical problem in this field.

[0006] In summary, while existing technologies have gradually evolved from traditional tumor treatment to targeted delivery, nanocarriers, and microneedle-based local drug delivery, they still fail to simultaneously address the following needs: firstly, achieving efficient, precise, and controllable delivery of active ingredients at the tumor site; secondly, reducing systemic toxicity and the adverse effects of the complex tumor microenvironment on therapeutic efficacy; thirdly, avoiding over-reliance on complex, cumbersome, and long-term safety uncertainties in artificial carrier systems; and fourthly, balancing material sourcing, preparation processes, cost control, and feasibility for subsequent clinical translation. Therefore, developing a novel local antitumor delivery material and its preparation technology that can overcome these shortcomings has significant research value and application prospects. Summary of the Invention

[0007] To address the problems existing in the prior art, the first objective of this invention is to provide a natural antimony chalcopyrite microneedle for cancer treatment. This microneedle utilizes the unique crystal structure and ionic composition of the mineral to act synergistically on tumor cells through multiple mechanisms, achieving excellent tumor treatment effects at relatively low doses. This effectively solves the technical problems of existing anticancer drugs having single targets, easy drug resistance, and significant toxic side effects.

[0008] The second objective of this invention is to provide a method for preparing natural antimony chalcopyrite microneedles for cancer treatment. This method, through mechanical refining and calcination activation, increases the specific surface area of ​​natural antimony chalcopyrite while also promoting the reorganization of the mineral's crystal lattice structure. Some sulfides are converted into oxides or sulfates, increasing lattice defects and thus significantly improving its dispersibility in solution.

[0009] A third objective of this invention is to provide an application of natural antimony chalcopyrite microneedles for cancer treatment, used in the preparation of antitumor drugs. Test results show that these microneedles exhibit excellent pH responsiveness. The activated natural antimony chalcopyrite can achieve a specific and large-scale release of target ions in an acidic system simulating the tumor microenvironment, while the release is significantly inhibited in a neutral system simulating the normal physiological environment. This characteristic allows the drug to efficiently kill tumors while minimizing toxic side effects on normal tissues, achieving highly efficient, low-toxicity, and precise treatment.

[0010] To achieve the above objectives, the present invention provides a method for preparing natural antimony chalcopyrite microneedles for cancer treatment, comprising: mechanically refining and calcining and activating natural antimony chalcopyrite sequentially, then adding it together with a gelling agent into deionized water and stirring evenly to obtain a precursor solution; then injecting the precursor solution into a microneedle mold and solidifying it to obtain the microneedle.

[0011] The particle size of the natural antimony chalcopyrite after mechanical refining is 25~55μm; the concentration of natural antimony chalcopyrite in the precursor fluid is 50~200g / L.

[0012] The natural antimony chalcopyrite used in this invention, after mechanical and calcination treatment, contains a variety of metal ions that can be released synergistically in the tumor microenvironment. It achieves a highly efficient anti-tumor effect through a multi-target, multi-pathway mechanism of action. The reason may be that its complex multi-element components can be released synchronously in the acidic tumor microenvironment, exerting a synergistic effect between ions and avoiding the problem of drug resistance easily generated by single-component drugs.

[0013] Furthermore, the ion release capacity of natural antimony chalcopyrite is significantly enhanced after mechanical refining and high-temperature roasting. After ball milling to micro-nano particle sizes, the specific surface area of ​​natural antimony chalcopyrite increases significantly, exposing more active sites. Subsequent high-temperature roasting reorganizes the mineral's crystal structure, converting some sulfides into oxides or sulfates, increasing lattice defects, and thus improving its solubility in solution. This treatment method fully utilizes the intrinsic multi-element advantages of natural minerals, achieving a controllable enhancement of ion release capacity through a combined physical-chemical activation approach.

[0014] As a preferred embodiment, the natural antimony copper comprises the following main components by mass percentage: Cu 33~37%, S 18~20%, Sb 10~13%, Fe 10~13%, O 8~10%, and As 6~8%.

[0015] As a preferred embodiment, the mechanical refining method is at least one of grinding, ball milling, and mineral milling.

[0016] As a preferred embodiment, the gelling agent is hyaluronic acid and / or sodium hyaluronate.

[0017] As a preferred embodiment, the mass ratio of the natural antimony copper to the gelling agent is 1:1 to 20.

[0018] As a preferred embodiment, the mechanical refining method is ball milling, with the following conditions: ball-to-material ratio of 8~16:1, grinding speed of 500~800 r / min, and time of 10~40 min.

[0019] As a preferred embodiment, the ball milling media is at least one of zirconium oxide, corundum, stainless steel, and agate.

[0020] As a preferred embodiment, the calcination and activation process is as follows: the mechanically refined natural antimony chalcopyrite is placed in a muffle furnace and calcined at 400~1200℃ for 0.5~2h, and then naturally cooled to room temperature to obtain the final product.

[0021] As a preferred embodiment, the precursor solution also contains an active ingredient at a concentration of 15–550 g / L.

[0022] As a preferred embodiment, the active ingredient is one or at least two of chitosan, alginate, or dextran.

[0023] As a preferred embodiment, the curing process is as follows: inject the precursor liquid into the PDMS microneedle mold, ventilate to accelerate solvent evaporation, and demold after complete drying to obtain the final product.

[0024] The present invention also provides a natural antimony chalcopyrite microneedle for cancer treatment, which is prepared by the method described in any one of the above.

[0025] This invention also provides an application of natural antimony chalcopyrite microneedles for cancer treatment, used in the preparation of antitumor drugs.

[0026] As a preferred embodiment, the tumor is one of melanoma, breast cancer, and Ehrlich ascites carcinoma.

[0027] The reason why the natural antimony chalcopyrite microneedles provided by this invention can produce excellent therapeutic effects on tumor-bearing mice is as follows: 1) After refining, the particle size of natural antimony chalcopyrite is reduced to the micro-nano scale, and the specific surface area is significantly increased, exposing more active sites; after high-temperature calcination, the mineral lattice structure is reorganized, some sulfides are converted into oxides or sulfates, and the lattice defects increase, which significantly improves its solubility in the acidic tumor microenvironment; 2) The activated mineral is rich in various elements such as Cu, S, As, Sb, Fe, and Mg, and can simultaneously release various metal ions in the acidic tumor microenvironment. Among them, copper ions can induce copper death in tumor cells. Iron ions can mediate the Fenton reaction to generate reactive oxygen free radicals, antimony and arsenic ions can interfere with mitochondrial function and energy metabolism in tumor cells, and magnesium ions participate in regulating the immune response in the tumor microenvironment. The synergistic effect of multiple ions acts on tumor cells simultaneously through multiple targets and pathways, which significantly improves the anti-tumor effect on the one hand, and effectively avoids the drug resistance that tumor cells are prone to develop to drugs with a single mechanism of action on the other hand. 3) The physical puncture effect of microneedles destroys the skin stratum corneum barrier and delivers activated minerals directly to the tumor tissue, avoiding the problems of low bioavailability and large toxic side effects of systemic administration, thereby achieving efficient, precise and safe anti-tumor treatment for tumor-bearing mice.

[0028] Compared with the prior art, the beneficial technical effects of the technical solution provided by the present invention are as follows:

[0029] 1) The natural antimony copper microneedles provided by this invention utilize the unique crystal structure and ionic composition of the mineral to act on tumor cells through multiple mechanisms, achieving excellent tumor treatment effects at low dosages. This effectively solves the technical problems of single target of anticancer drugs, easy drug resistance and large toxic side effects in the prior art. In addition, the microneedles have good biodegradability. The matrix material degrades into water and carbon dioxide, and the mineral degradation products are trace elements essential to the human body. They have no long-term cumulative toxicity to the environment and organisms, no immunogenicity, no bone marrow suppression or other serious side effects.

[0030] 2) The preparation method provided by this invention, through mechanical refinement and calcination activation, increases the specific surface area of ​​natural antimony chalcopyrite while also promoting the reorganization of the mineral lattice structure. Some sulfides are converted into oxides or sulfates, increasing lattice defects, thereby significantly improving its solubility in solution. This method fully utilizes the intrinsic multi-element advantages of natural minerals, achieving controllable enhancement of ion release capacity. At the same time, this method directly utilizes mineral resources without the need for complex chemical synthesis, and has the natural advantages of wide availability and low cost.

[0031] 3) The technical solution provided by this invention, based on the specificity of the aforementioned microneedles, demonstrates excellent technical effects when used to prepare antitumor drugs. Test results show that the microneedles exhibit excellent pH responsiveness. Activated natural antimony chalcopyrite can achieve a large-scale specific release of target ions in an acidic system simulating the tumor microenvironment, while the release is significantly inhibited in a neutral system simulating the normal physiological environment. This characteristic enables the drug to efficiently kill tumors while minimizing toxic side effects on normal tissues, achieving highly efficient, low-toxicity, and precise treatment. Attached Figure Description

[0032] Figure 1 This is a particle size analysis diagram of the natural antimony copper used in this invention after different mechanical activation times;

[0033] Figure 2 The XRD patterns of the natural antimony copper used in this invention after activation at different calcination temperatures are shown.

[0034] in, Figure 2 (a) is the generating phase. Figure 2 (b) is the corresponding PDF card;

[0035] Figure 3 The graph shows the ion release results of the natural antimony copper used in this invention after activation at different calcination temperatures, simulating the tumor microenvironment and neutral environment.

[0036] Figure 4 This is a comparison of the ion dissolution of antimony black copper after calcination and activation at 400℃ and the original ore at different times.

[0037] Figure 5 This is a graph showing the ion dissolution results of antimony copper after calcination and activation at 400℃ at different times according to the present invention.

[0038] Figure 6 This is a morphological diagram of the microneedles provided in Embodiment 1 of the present invention;

[0039] Figure 7 These are mechanical property test diagrams of the microneedles provided in Embodiments 1 and 11-14 of the present invention;

[0040] Figure 8 This is a solubility test diagram of the microneedles provided in Embodiment 1 of the present invention;

[0041] Figure 9 This is a graph showing the change in tumor volume after micro-targeted treatment of mouse tumors provided in Example 1 of the present invention. Detailed Implementation

[0042] The following provides a detailed description of specific embodiments of the present invention. Obviously, the described embodiments and comparative examples are only a part of the present invention, and not all of it. All other examples based on the embodiments of the present invention, modified or refined by those skilled in the art, fall within the scope of protection of the present invention.

[0043] The natural antimony copper used in the following examples and comparative examples is from the same source as natural sulfide mineralization, and its main mass percentage elements are:

[0044]

[0045] Example 1

[0046] This embodiment provides a natural antimony tetrahedrite microneedle, the preparation process of which is as follows:

[0047] 1. Weigh 8g of antimony chalcopyrite sample and mix it with zirconium oxide grinding balls at a mass ratio of 1:10. Put the mixture into a ball mill jar, set the ball mill speed to 600r / min, and keep it running at this speed for 10 minutes before taking it out.

[0048] 2. Place the ball-milled antimony copper ore in a quartz crucible, put the quartz crucible into a muffle furnace, and roast it at 400°C for 1 hour;

[0049] 3. Weigh 0.1g of roasted antimony copper ore and 0.5g of sodium hyaluronate, add 1mL of deionized water, stir magnetically until the material is completely dissolved, and obtain the precursor solution after centrifugation and degassing.

[0050] 4. Transfer the above-mentioned precursor liquid into the PDMS microneedle mold, and use a vacuum-assisted filling process to allow the liquid to enter the mold cavity. Turn on the ventilation equipment to accelerate solvent evaporation. After it is completely dry, demold to obtain mineral-loaded slow-release microneedles.

[0051] Example 2

[0052] This embodiment is exactly the same as Embodiment 1, except that the ball milling time is 15 minutes.

[0053] Example 3

[0054] This embodiment is exactly the same as Embodiment 1, except that the ball milling time is 20 minutes.

[0055] Example 4

[0056] This embodiment is exactly the same as Embodiment 1, except that the ball milling time is 25 minutes.

[0057] Example 5

[0058] This embodiment is exactly the same as Embodiment 1, except that the ball milling time is 30 minutes.

[0059] Example 6

[0060] This embodiment is exactly the same as Embodiment 1, except that the calcination temperature is 600℃.

[0061] Example 7

[0062] This embodiment is exactly the same as Embodiment 1, except that the calcination temperature is 800℃.

[0063] Example 8

[0064] This embodiment is exactly the same as Embodiment 1, except that the calcination temperature is 1000℃.

[0065] Example 9

[0066] This embodiment is exactly the same as Embodiment 1, except that the calcination temperature is 1200℃.

[0067] Example 10

[0068] This embodiment is exactly the same as Embodiment 1, except that the calcination temperature is 1000℃.

[0069] Example 11

[0070] This embodiment is exactly the same as Embodiment 1, except that the mass ratio of activated mineral to sodium hyaluronate is 1:1.

[0071] Example 12

[0072] This embodiment is exactly the same as Embodiment 1, except that the mass ratio of activated mineral to sodium hyaluronate is 1:2.

[0073] Example 13

[0074] This embodiment is exactly the same as Embodiment 1, except that the mass ratio of activated mineral to sodium hyaluronate is 1:10.

[0075] Example 14

[0076] This embodiment is exactly the same as Example 1, except that the mass ratio of activated mineral to sodium hyaluronate is 1:20.

[0077] Comparative Example 1

[0078] This comparative example is exactly the same as Example 1, except that the ball milling time is 5 minutes.

[0079] Tests were conducted on the minerals after ball milling for different times, and the particle size distribution was measured using a laser particle size analyzer, resulting in particle size distribution curves. The results showed that as the ball milling time increased from 0 min to 30 min, the particle size distribution range of the minerals gradually narrowed, and the distribution curve exhibited a single-peak distribution with a sharper peak, indicating a tendency for particle size concentration. Simultaneously, the peak position of the particle size distribution curve gradually shifted towards smaller particle sizes, indicating that the particles gradually became finer with increasing ball milling time. Comparative analysis of the particle size distribution curves from Examples 1 to 5 revealed that the mineral particle size reached its finest level under the ball milling condition in Example 4; beyond this condition, the particle size increased significantly, demonstrating superior performance compared to other ball milling conditions. The experiments prove that the conditions in Example 4 are beneficial for improving the particle size uniformity of the minerals and achieving micro-refinement, laying a solid material foundation for subsequent calcination activation and ion release performance enhancement.

[0080] This invention also uses X-ray diffraction to analyze the phase composition of antimony chalcopyrite after roasting at different temperatures, and the results are as follows: Figure 2 As shown. By Figure 2 It was found that under calcination at 400℃, significant cuprous oxide (Cu₂O) characteristic peaks and other characteristic diffraction peaks of readily soluble active phases were detected in the mineral characteristic diffraction peaks, with peak intensities and peak areas significantly higher than those at 600, 800, 1000, and 1200℃. In contrast, the calcination products at 600, 800, 1000, and 1200℃ produced more inert oxide phases. Experiments demonstrate that a calcination temperature of 400℃ is more conducive to the directional transformation of active components in antimony chalcopyrite, generating more readily soluble and highly active therapeutic ion precursor phases. This provides sufficient theoretical basis and material foundation for subsequent pH-responsive ion leaching in the tumor microenvironment and in vivo antitumor experiments.

[0081] In Example 1 of this invention, ion leaching experiments were conducted on the sample in a normal physiological environment with a pH of 7.0-7.5 and a tumor microenvironment with a pH of 5.0-6.5, respectively; results Figure 3 This indicates that, compared to the normal physiological environment, the tumor microenvironment, in an acidic system, provides a higher concentration of therapeutic ions (Cu). 2+ The cumulative dissolution concentration of the substance reached 5314.54 ppm / cm³ within 1 hour. 3 In a neutral system, under the same conditions, the ion dissolution concentration was only 2358.32 ppm / cm³. 3 ,Depend on Figure 4 It can be seen that the therapeutic ions from roasting activated minerals are 20 to 30 times higher than those from the original ore. Figure 5 It can be seen that the target therapeutic ions reached as high as 5837.73 ppm / cm² within 5 minutes in the tumor microenvironment. 3Experiments have shown that the calcined and activated minerals possess significant pH-responsive ion release characteristics, enabling them to specifically release therapeutic ions in the acidic microenvironment of tumors, while this release behavior is significantly inhibited in normal physiological environments, laying the foundation for subsequent precision treatment of tumor sites. Furthermore, from... Figure 3 , Figure 5 as well as Figure 4 It can be seen that the calcined and activated minerals achieve excellent therapeutic ion release effects under simulated tumor microenvironment conditions, laying the foundation for subsequent tumor treatment and demonstrating the feasibility of using them as natural mineral pharmaceutical materials for tumor treatment.

[0082] The morphology of the microneedles obtained in Example 1 was observed, and the results are as follows: Figure 6 As shown in the figure, the microneedle array prepared by this invention is regularly arranged, with complete needle morphology, smooth and defect-free surface, sharp and uniform needle tips, and needle height and spacing that meet the design expectations, indicating that the microneedle preparation process of this invention has good formability and repeatability. Experiments demonstrate that the microneedles prepared by the method of this invention exhibit excellent integrity and uniformity in their microstructure, providing a reliable structural guarantee for subsequent skin puncture performance and drug release effects. The mechanical effects of Examples 1 and Examples 11-14 are described by... Figure 7 It can be seen that the microneedle patches prepared by the present invention with different ratios all exhibit good mechanical strength in mechanical property tests. The axial compression failure force test of the needle body was conducted using a texture analyzer. The results showed that the needle failure force of each microneedle formulation was above 60N, which is greater than the minimum skin penetration force threshold (13.05 N), indicating that the microneedles of the present invention can meet the mechanical requirements for skin puncture.

[0083] Furthermore, the present invention also conducted a skin solubility test on the microneedles obtained in Example 1. The procedure was as follows: Fresh detached pigskin was taken, the subcutaneous fat layer and connective tissue were removed, and the skin was cleaned and fixed for later use. The prepared microneedles were tightly applied to the surface of the pigskin, and a certain pressure was applied and pressed continuously for 2 minutes to ensure that the microneedles were completely inserted into the stratum corneum of the skin. The pigskin with the microneedles applied was then left to stand. Samples were taken at time points of 0 min, 1 min, 3 min, 5 min and 8 min after the start of incubation. The microneedles were carefully removed and placed under an optical microscope to observe the changes in the microscopic morphology of the needle body. The dissolution of the needle tip and the degree of needle body residue were recorded by photograph. The test results are as follows. Figure 8 As shown in the test, the microneedles prepared in this invention were observed to be almost completely dissolved in the in vitro pig skin dissolution experiment. When the sample was taken 5 minutes after application, the microneedle body was almost completely dissolved, the needle tip structure was basically disappeared, and the needle body height residual rate was 6-10%. When the sample was taken 8 minutes later, the microneedle body was completely dissolved, and there was no needle-like structure residue on the surface of the microneedle patch substrate.

[0084] To further verify the superior technical effect of the microneedles provided by this invention in tumor treatment, mouse experiments were also conducted. The procedure was as follows: Tumor-bearing mice were inoculated with melanoma and then randomly divided into groups of no fewer than 9 animals each. The microneedles of this invention were applied to the peritumoral area of ​​the tumor in the mice. After each application, gentle pressure was applied for 2-3 minutes to ensure the needle penetrated the skin. The patch was changed every 48 hours, and the treatment cycle was 7-15 days. During the treatment period, the long and short diameters of the tumor were measured every 2 days, and the data were recorded. After treatment, the mice were euthanized by cervical dislocation, the tumor tissue was dissected and separated, washed with physiological saline, dried, and the tumor weight was recorded. Meanwhile, mice that received no treatment served as a blank control group. The test results are as follows: Figure 9 As shown in the figure, the results indicate that, compared with the blank control group, the tumor volume of mice in the microneedle administration group at the end of treatment was 204.31 ± 82.68 mm. 3 In contrast, the tumor volume in the control group mice was as high as 1542.53 ± 298.19 mm. 3 Because the activated minerals loaded on microneedles continuously release ions in the acidic tumor microenvironment, inducing immunogenic death of tumor cells, they exhibit excellent therapeutic effects on tumors in mice. Therefore, this invention prepares drug-loaded microneedle patches by activating natural minerals. Through their specific release of therapeutic ions in the acidic tumor microenvironment and induction of immunogenic death of tumor cells, they achieve significant inhibition of tumor volume in tumor-bearing mice, demonstrating excellent anti-tumor efficacy and tumor microenvironment responsive therapeutic advantages.

Claims

1. A method for preparing natural antimony chalcopyrite microneedles for cancer treatment, characterized in that, include: Natural antimony chalcopyrite is mechanically refined and calcined and activated sequentially, then added together with a gelling agent to deionized water and stirred evenly to obtain a precursor solution. The precursor solution is then injected into a microneedle mold and solidified to form the final product. The particle size of the natural antimony chalcopyrite after mechanical refining is 25~55μm; the concentration of natural antimony chalcopyrite in the precursor fluid is 50~200g / L.

2. The method for preparing natural antimony chalcopyrite microneedles for cancer treatment according to claim 1, characterized in that: The mechanical refining method is at least one of grinding, ball milling and mineral milling; the gelling agent is hyaluronic acid and / or sodium hyaluronate.

3. The method for preparing natural antimony chalcopyrite microneedles for cancer treatment according to claim 1, characterized in that: The mechanical refining method is ball milling, with the following conditions: ball-to-material ratio of 8 to 16:1, grinding speed of 500 to 800 r / min, and time of 10 to 40 min; the ball milling medium is at least one of zirconium oxide, corundum, stainless steel, and agate.

4. The method for preparing natural antimony chalcopyrite microneedles for cancer treatment according to claim 1, characterized in that: The calcination and activation process is as follows: the mechanically refined natural antimony copper ore is placed in a muffle furnace and calcined at 400~1200℃ for 0.5~2h, and then naturally cooled to room temperature to obtain the final product.

5. The method for preparing natural antimony chalcopyrite microneedles for cancer treatment according to claim 1, characterized in that: The precursor solution also contains active ingredients at a concentration of 15–550 g / L.

6. The method for preparing natural antimony chalcopyrite microneedles for cancer treatment according to claim 5, characterized in that: The active ingredient is one or at least two of chitosan, alginate, or dextran.

7. The method for preparing natural antimony chalcopyrite microneedles for cancer treatment according to claim 1, characterized in that: The curing and molding process is as follows: inject the precursor liquid into the PDMS microneedle mold, ventilate to accelerate solvent evaporation, and demold after complete drying to obtain the final product.

8. A natural antimony chalcopyrite microneedle for cancer treatment, characterized in that: It is prepared by the method described in any one of claims 1 to 7.

9. The application of the natural antimony chalcopyrite microneedles for cancer treatment as described in claim 8, characterized in that: Used in the preparation of anti-tumor drugs.

10. The application of a natural antimony chalcopyrite microneedle for cancer treatment according to claim 9, characterized in that: The tumor is one of melanoma, breast cancer, or Ehrlich ascites carcinoma.

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