Dual-power liposome nano motor and preparation method and application thereof

Abstract

The invention belongs to the technical field of the crossing field of nano biological materials and intelligent drug delivery systems, and discloses a dual-power liposome nano motor and a preparation method and application thereof, the dual-power liposome nano motor comprises liposome, metal nanoparticles and DNAzyme, the metal nanoparticles have catalase-like activity, and the DNAzyme has the activity similar to catalase. The metal nanoparticles and the DNAzyme are entrapped by the lipidosome. The dual-power liposome nano-motor provided by the invention is applied to tumor treatment, gene therapy regulates gene expression to inhibit tumor growth, chemodynamic therapy can destroy tumor cells through chemical reaction of drugs, and photodynamic therapy energy is transmitted to surrounding oxygen, so that the tumor cells are prevented from being damaged. According to the present invention, the three treatment modes are combined to form the complementary advantages, such that the treatment effectiveness is improved, and the occurrence of the adverse reaction is reduced; the singlet oxygen with the strong activity is subjected to the oxidation reaction with the nearby biological macromolecules, and the generated cytotoxicity can kill the cancerous cells; and the three treatment modes are combined together so as to form the complementary advantages, such that the treatment effectiveness is improved, and the occurrence of the adverse reaction is reduced.

Description

A dual-drive liposome nanomotor, its preparation method and application Technical Field

[0001] This invention belongs to the interdisciplinary technical field of nanobiomaterials and intelligent drug delivery systems, and specifically relates to a dual-powered liposome nanomotor, its preparation method, and its application. Background Technology

[0002] Globally, approximately two million women are diagnosed with breast cancer each year, and about six hundred thousand die from it. According to the latest statistics released by the International Agency for Research on Cancer (IARC) of the World Health Organization, breast cancer has surpassed lung cancer for the first time to become the most common cancer worldwide. As a superficial tumor, it primarily occurs in the lining of the mammary ducts, epithelial tissue, or lobules, and exhibits varying degrees of metastasis, invasiveness, and heritability. Furthermore, breast cancer is the leading cause of cancer incidence and mortality among women worldwide. Breast cancer not only severely impacts the physical and mental health of the individual patient but also places a significant burden on families and society. Treatment for breast cancer depends on the cancer subtype and the extent of spread from the breast to lymph nodes (stage II or III) or other parts of the body (stage IV). Currently, clinical treatments for breast cancer mainly include surgical resection, radiation therapy, hormone therapy, chemotherapy, or targeted biological therapy. However, traditional treatments suffer from serious side effects and toxicity, drug resistance, lack of personalized treatment, and risks of recurrence and metastasis. Therefore, there is an urgent need to develop a superior treatment method for breast cancer.

[0003] Nanomotors are a novel class of drug delivery carriers capable of converting the chemical energy of their surroundings or external energy sources into the mechanical power required for autonomous movement. Due to their autonomous driving force, unlike other drug carriers, nanomotors offer the possibility of efficient drug penetration into cells and tissues. Most importantly, the motility of nanomotors can significantly accelerate the interaction between target molecules and the nanomotors, thereby greatly improving capture or catalytic efficiency. However, most current nanomotors are primarily based on inorganic nanomaterials, but most of these materials lack degradability, and their biocompatibility needs further confirmation. Therefore, developing nanomotors with sufficient dynamics to target lesion sites, while requiring substrates with good biocompatibility, is of great significance. The tumor microenvironment is characterized by abnormal vascular systems, dense extracellular matrix, and increased interstitial fluid pressure, leading to limited drug penetration at target sites. Developing nanomotors with highly efficient driving force specifically for breast cancer lesions is a challenging problem. This will help overcome various difficulties faced by traditional treatment methods, providing a more reliable and effective solution for breast cancer treatment, and has significant clinical implications. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention proposes a dual-dynamic liposome nanomotor, its preparation method, and its applications. The dual-dynamic liposome nanomotor provided by this invention, when applied to tumor treatment, can achieve synergistic effects of gene therapy, chemokinetic therapy, and photodynamic therapy. It inhibits tumor growth by precisely delivering gene therapy drugs to the tumor site and regulating gene expression. Chemokinetic therapy destroys tumor cells through the chemical reaction of the drug. Photodynamic therapy transfers energy to surrounding oxygen, generating highly reactive singlet oxygen that reacts with nearby biomolecules, producing cytotoxic properties that kill cancerous cells. The combination of these three treatment methods creates complementary advantages, improving treatment effectiveness while reducing adverse reactions.

[0005] Specifically, the first objective of this invention is to provide a dual-powered liposome nanomotor, comprising liposomes and metal nanoparticles, wherein the liposomes are loaded with IR808, and the metal nanoparticles have catalase-like activity, and the metal nanoparticles are encapsulated by the liposomes.

[0006] Furthermore, the liposomes are DOPC liposomes.

[0007] Furthermore, the metal nanoparticles are gold-manganese nanoparticles.

[0008] Furthermore, the mass ratio of the metal nanoparticles to the liposomes is 8-11:1.

[0009] Furthermore, it also includes a DNAzyme, which is encapsulated within the liposome.

[0010] Furthermore, the DNAzyme is a cholesterol-modified DNAzyme.

[0011] The dual-powered liposome nanomotor has an asymmetric structure.

[0012] The second objective of this invention is to provide a method for a dual-powered liposome nanomotor, characterized by comprising the following steps: (1) preparing gold nanoparticles; (2) mixing the gold nanoparticles obtained in step (1) with potassium permanganate in a solution, and then adding polycyclic aromatic hydrocarbons to the solution to react and obtain gold / manganese nanoparticles; (3) loading IR808 onto DOPC liposomes; (4) mixing and incubating the gold / manganese nanoparticles obtained in step (2) with the IR808-loaded DOPC liposomes obtained in step (3) in a certain proportion to obtain a gold / manganese / liposome complex, wherein the mass ratio of the metal nanoparticles to the liposomes is 8-11:1; and then adding DNAzyme to the gold / manganese liposome complex solution for incubation to obtain a dual-powered liposome nanomotor.

[0013] Further, in step (3), the mixing ratio of DNAzyme and manganese gold liposome complex is: 1 nM / L DNAzyme to 1-3 μg / mL manganese gold liposome complex.

[0014] A third objective of this invention is to provide the application of dual-powered liposome nanomotors in the treatment of tumors.

[0015] Furthermore, the tumor is breast cancer.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The dual-powered liposome nanomotor provided by the present invention includes DOPC liposomes loaded with IR808, metal nanoparticles, and DNAzyme. Applying the dual-powered liposome nanomotor to the treatment of breast cancer can accurately deliver gene therapy drugs to the tumor site, achieve targeted treatment, reduce damage to healthy tissues, and reduce the occurrence of adverse reactions.

[0017] (2) The dual-dynamic liposome nanomotor provided by this invention comprises DOPC liposomes loaded with IR808, metal nanoparticles, and DNAzyme, combining the advantages of gene therapy, chemokinetic therapy, and photodynamic therapy to achieve synergistic effects of the three treatment methods. Gene therapy can inhibit tumor growth by regulating gene expression; chemokinetic therapy can destroy tumor cells through the chemical reaction of drugs; photodynamic therapy transfers energy to the surrounding oxygen, generating highly reactive singlet oxygen, which can react with nearby biomolecules to produce cytotoxicity and kill diseased cells, thereby achieving a more comprehensive therapeutic effect. At the same time, the O2 generated by the degradation of MnO2 in the metal nanoparticles can solve the defect of poor photodynamic therapy effect due to insufficient O2 in the tumor area. The application of the dual-dynamic liposome nanomotor allows these three treatment methods to be better combined, forming complementary advantages and improving the effectiveness of treatment.

[0018] (3) The dual-powered liposome nanomotor provided by this invention uses metal nanoparticles and IR808 as the power core, DOPC liposomes as the backbone carrier, and DNAzyme as the functional execution unit. The three are integrated to form a complete liposome-based composite system with autonomous movement capability. The entire composite is the nanomotor, which has good biocompatibility and biodegradability, reducing toxic side effects on the human body and improving the safety of treatment. The small size and special surface properties of the nanomotor also enable drugs to penetrate tumor tissue better, increasing the local drug concentration and further enhancing the therapeutic effect.

[0019] (4) The dual-powered liposome nanomotor provided by the present invention has an asymmetric structure. By controlling the mass of metal nanoparticles and liposomes to be in the range of 8-11:1, about 50% Au / Mn nanoparticles are adsorbed on the surface of the liposomes. Since the membrane structure of the liposomes has a fluid surface Au / Mn in an aggregated state, the cholesterol-modified DNAzyme can be inserted into the remaining space of the liquid liposomes to form the asymmetric structure of the dual-powered liposome nanomotor. Attached Figure Description

[0020] Figure 1 shows the comparison of loading rates of nanoparticles and liposomes at different mass ratios; Figure 2 shows the fluorescence changes of liposome nanomotors loaded with different concentrations of DNAzyme; Figure 3 shows the catalase-like activity assay of the nanomotors; Figure 4 shows the dynamics of the nanomotors decomposing hydrogen peroxide to produce oxygen; Figure 5 shows the agarose gel electrophoresis analysis of the DNAzyme cleaving mRNA by the dual-dynamic nanomotors; Figure 6 shows the trajectory tracking of the dual-dynamic liposome nanomotors; Figure 7 shows the tumor cell targeting performance of the dual-dynamic liposome nanomotors; Figure 8 shows the evaluation of the anti-tumor effect of the dual-dynamic liposome nanomotors; Figure 9 shows a transmission electron microscope image of the dual-dynamic liposome nanomotors. Detailed Implementation

[0021] The first objective of this application is to provide a dual-powered liposome nanomotor, comprising DOPC liposomes loaded with IR808, metal nanoparticles, and a DNAzyme. The DNAzyme is a cholesterol-modified DNAzyme. The metal nanoparticles possess catalase-like activity, and the metal nanoparticles and DNAzyme are encapsulated by the liposomes. The metal nanoparticles include gold-manganese nanoparticles (gold-manganese nanoparticles are composite nanosystems formed by physical adsorption, chemical bonding, or co-precipitation of gold nanoparticles and manganese-based nanoparticles, with a common "core-shell" structure, such as Au as the core and MnO2 as the shell). The dual-powered liposome nanomotor in this scheme uses DOPC liposomes (DOPC liposomes are neutral phospholipid liposomes prepared with 1,2-dioleoyl-sn-glycerol-3-phosphocholine (DOPC) as the main membrane material, and DOPC molecules self-assemble to form closed phospholipid bilayer vesicles) as the framework carrier, and metal nanoparticles and IR808 (IR808 is a hydrophobic squaric acid cyanine near-infrared II (NIR-II) bifunctional dye) as the power core. The power sources of the dual-powered nanomotor are: on the one hand, Au / Mn nanoparticles with catalase activity can decompose the high concentration of hydrogen peroxide in the tumor area into water and oxygen, and the generated gas can serve as a propulsion force; on the other hand, cholesterol-modified DNAzyme can target EGR-1 mRNA highly expressed in breast cancer cells. Therefore, the DNAzyme-loaded nanomotor has chemotaxis towards tumor cells. At the same time, the two power sources generate in the same direction, so they can generate a co-directional propulsion force to propel the nanomotor towards the tumor area.

[0022] Furthermore, the dual-drive liposome nanomotor in this scheme includes DOPC liposomes loaded with IR808, metal nanoparticles, and cholesterol-modified DNAzyme. The DOPC liposomes act as a framework carrier, encapsulating the metal nanoparticles in an internal water cavity and the DNAzyme in a lipid bilayer. IR808 is embedded in a hydrophobic bilayer. These three components construct a dual-drive liposome nanomotor. Their synergistic effect is not a simple functional superposition, but rather a closed-loop synergy encompassing the autonomous movement characteristics of the nanomotor, forming a comprehensive system of drive, delivery, therapy, stabilization, and regulation. In addition to their original gene therapy, chemokinetic therapy, and photodynamic therapy effects, the three components also synergistically enhance each other: the DOPC liposomes, as the framework carrier, ensure the system's biocompatibility and delivery basis, providing a physically stable framework for the entire system; encapsulating the metal nanoparticles in an internal water cavity and the DNAzyme in a lipid bilayer; and embedding IR808 in a hydrophobic bilayer, achieving spatial separation and uniform dispersion of each functional component, effectively preventing the aggregation of metal particles, and simultaneously providing a stable environment for the DNAzyme. Providing a stable aqueous environment prevents the randomized coiling of metal nanoparticles from dispersing at the DNAzyme molecular level. The hypoxia, low pH, and nuclease enrichment in the tumor microenvironment are core reasons for the low efficiency of DNAzyme gene therapy. The synergistic regulation of metal nanoparticles and DOPC liposomes, providing O2 and an acidic environment, enhances DNAzyme activity. DOPC liposomes encapsulate DNAzymes within an internal lipid bilayer, isolating them from nucleases in the tumor microenvironment and preventing DNAzyme degradation. Simultaneously, the stable ionic environment of the liposome's aqueous cavity ensures the modification efficiency of metal ions and DNAzymes, maintaining the stability of its catalytic domain. The mutual stability between metal particles and DNAzymes is also achieved through metal ion modification of the catalytic domains formed by DNAzymes. This synergistic effect allows the dual-powered liposome nanomotor provided in this application to possess both effective tumor cell targeting and biodegradable components, making it adaptable to the complex breast cancer treatment microenvironment and exhibiting good low toxicity and biocompatibility.

[0023] In this method, during the preparation of dual-powered liposome nanomotors, gold-manganese nanoparticles are first directionally adsorbed onto the surface of DOPC liposomes. The interaction between the gold-manganese nanoparticles and the liposome membrane alters the original liquid crystal phase structure of the liposomes, causing the adsorption area to locally transform into a colloidal phase and exhibit a tendency for micro-aggregation. This structural change provides vacant, insertable sites for the efficient loading of DNAzymes onto the liposome surface, allowing the DNAzymes to insert into the other end of the metal nanoparticle aggregation on the liposome structure, forming an asymmetrical structure. In this asymmetrical structure, the dual-powered core (gold-manganese nanoparticles) is concentrated at one end of the liposome. When O2 microbubbles are catalyzed and generated, the bubbles are released directionally only from the powered side. The recoil force propels the nanomotors to move linearly towards the non-powered side, actively targeting the tumor region. In contrast, in the symmetrical structure, the powered core is uniformly dispersed, and the bubbles are released from all sides. The recoil forces cancel each other out, and the motor exhibits random Brownian motion, unable to actively penetrate the tumor stroma, thus failing to achieve the effect of the symmetrical structure.

[0024] The present invention will be further illustrated below with reference to specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field.

[0025] Example 1

[0026] This embodiment provides a method for preparing a dual-powered liposome nanomotor, including the following steps: (1) Preparation of gold nanoparticles: Take 1% chloroauric acid aqueous solution and 1% sodium citrate aqueous solution in a volume ratio of 1:1 and boil for 30 min. Obtain a gold nanoparticle suspension through redox reaction and cool to room temperature for later use; Polyethylene glycol modification and purification: Take the above gold nanoparticle suspension and take the suspension containing gold nanoparticles (the gold nanoparticle suspension is calculated based on the weight of gold nanoparticles) in a weight ratio of 1:10 and mix with lipoic acid-polyethylene glycol (LA-PEG). Disperse in an ice bath for 30 min by ultrasonication, and then continue to react for 6 h at room temperature of 25±2℃, in the dark, under magnetic stirring conditions to obtain crude polyethylene glycol-modified gold nanoparticles; Put the crude product into a dialysis bag with a molecular weight cutoff of 3500 Da and dialyze with ultrapure water as the dialysis medium for 24 hours. The ultrapure water was replaced every 6 hours to remove unreacted lipoic acid-polyethylene glycol and byproducts, thus obtaining purified polyethylene glycol-modified gold nanoparticles.

[0027] (2) Mix 100 mL of the solution containing 10 mg gold nanoparticles obtained in step (1) with 42 mg potassium permanganate for 5 min under stirring. Then add 1 mL of solution containing 50 mg polycyclic aromatic hydrocarbons. React at room temperature for 1 hour. Centrifuge to collect the product and obtain gold manganese nanoparticles.

[0028] (3) Dissolve a certain amount of DOPC liposomes in chloroform to obtain a final concentration of 25 mg / mL. Remove the chloroform solvent and vacuum dry overnight at room temperature to form a uniform film. Add 500 μL of buffer to obtain a final concentration of 5 mg / mL, sonicate, and incubate overnight. Pass the suspension through a liposome extruder to obtain DOPC liposomes of uniform size. Add 1.16 μL of 10 mM photosensitizer IR808, sonicate, hydrate overnight, and then pass through a liposome extruder to obtain DOPC liposomes loaded with IR808.

[0029] (4) The gold-manganese nanoparticles obtained in step (2) and the DOPC liposomes loaded with IR808 obtained in step (3) were mixed in a certain ratio and incubated overnight. The gold-manganese nanoparticles and liposomes (the liposomes used for calculating the mass ratio here are DOPC liposomes, not IR808-loaded liposomes) were mixed in a mass ratio of 10:1, and then sodium chloride with a final concentration of 100 mM was added and incubated for another 30 min. The gold-manganese liposome complex was obtained by centrifugation. Then, 5 nM / L cholesterol-modified DNAzyme was added to 5 μg / mL of the gold-manganese liposome complex solution and incubated for 6 h. The excess cholesterol-modified DNAzyme was removed by centrifugation. After resuspending the precipitate in HEPES (4-hydroxyethylpiperazine ethanesulfonic acid) buffer, a dual-powered liposome nanomotor was obtained, as shown in Figure 9. The dual-powered liposome nanomotor has an asymmetric structure.

[0030] Comparative Example 1 This comparative example provides a gold nanoparticle-liposome-DNAzyme complex. The difference between this comparative example and Example 1 is that the gold manganese nanoparticles added in step 4, which are obtained in step (2), are replaced with polyethylene glycol modified gold nanoparticles obtained in step (1) and DOPC liposomes loaded with IR808 obtained in step (3) and mixed and incubated in the same ratio to obtain the gold nanoparticle-liposome-DNAzyme complex.

[0031] Experimental Example 1. Loading Rate Experiment of Metal Nanoparticles and Liposomes at Different Mass Ratios: Gold nanoparticles and gold-manganese nanoparticles prepared in steps (1) and (2) of Example 1 were mixed with rhodamine-labeled DOPC liposomes at different mass ratios and incubated with sodium chloride. After centrifugation to precipitate the nanoparticle / liposome complex, the supernatant was collected. At the same time, DOPC liposomes of the same concentration were used as a control, and the liposome adsorption efficiency was calculated based on the fluorescence intensity of the supernatant after centrifugation and the DOPC liposomes of the same concentration.

[0032] As shown in Figure 1, the results indicate that gold nanoparticles and gold-manganese nanoparticles can be effectively adsorbed on the surface of liposomes. Furthermore, when the mass ratio of metal nanoparticles to liposomes is 10:1, the adsorption efficiencies of liposomes for gold and gold-manganese nanoparticles are 53.53% and 63.22%, respectively.

[0033] 2. Fluorescence changes of liposome nanomotor loaded with different concentrations of DNAzyme: Different concentrations (5, 10, 25, 50 nM) of cholesterol-modified DNAzyme were added to the gold manganese liposome complex prepared in step (4) of Example 1, and the mixture was incubated at room temperature for 6 h. After centrifugation, the concentration of free DNA in the supernatant was measured.

[0034] As shown in Figure 2, the results indicate that the liposome nanomotor assembled with a 5 nM DNAzyme and a 5 μg / mL gold manganese liposome complex can achieve a DNAzyme loading rate of over 98%.

[0035] 3. Assay of Catalase-like Activity of Nanomotors: Gold nanoparticles, gold-manganese nanoparticles, and dual-powered liposome nanomotors prepared in steps (1), (2), and (4) of Example 1 were reacted with 3,3',5,5'-tetramethylbenzidine and 2 mM hydrogen peroxide in 20 mM acetate (pH 4.11) for 20 minutes. The absorbance at 652 nm was measured and recorded.

[0036] As shown in Figure 3, the results indicate that both gold manganese nanoparticles and dual-powered liposome nanomotors possess catalase-like activity, and the assembly process of the nanomotors does not affect enzyme activity.

[0037] 4. Test on the ability of nanomotors to decompose hydrogen peroxide to produce oxygen: The gold nanoparticles, gold manganese nanoparticles, and dual-power liposome nanomotor solutions obtained in steps (1), (2), and (4) of Example 1 were passed through nitrogen gas to remove oxygen from the solution, and then H2O2 was added. The amount of oxygen generated and the decomposition rate of H2O2 were measured.

[0038] As shown in Figure 4, the results indicate that the dual-powered liposome nanomotor has good catalase-like activity and can rapidly decompose H2O2, with a maximum dissolved oxygen concentration of 18.96 mg / L.

[0039] 5. DNAzyme mRNA cleavage performance test of dual-powered nanomotor: The dual-powered liposome nanomotor obtained in step (4) of Example 1 and the gold nanoparticle-liposome-DNAzyme complex prepared in step (4) of Comparative Example 1 were incubated with substrate mRNA, and the nucleic acid products were separated by 1% agarose gel. Due to the degradation of MnO2, Mn... 2+ It can provide the metal cofactors necessary for DNAzyme to cleave the corresponding RNA.

[0040] As shown in Figure 5, the results indicate that the dual-powered liposome nanomotor has the ability to cleave mRNA.

[0041] 6. Motion Trajectory Tracking Experiment of Dual-Powered Nanomotors: The dual-powered liposome nanomotors obtained in Example 1 were mixed with gold nanoparticles prepared in step (1) of Example 1 and DOPC liposomes loaded with IR808 prepared in step (3) of Example 1 at a mass ratio of 10:1 to obtain a gold-liposome complex (as a control group). The motion behavior of the liposome nanomotors was recorded using nanoparticle tracking analysis technology. Videos of nanoparticle motion were recorded (speed 25 frames / second, duration of each video 5 seconds). Ten nanoparticles were tracked in each experiment, and the x and y trajectories of the tracked nanoparticles were analyzed.

[0042] As shown in Figure 6, the results indicate that the dual-power nanomotor exhibits significantly more directional propulsion motion compared to the control group.

[0043] 7. Tumor cell targeting test of dual-powered nanomotors: The dual-powered liposome nanomotors obtained in Example 1 were moved in a model of tumor cells of different densities (upper layer:lower layer = 1:2, motor moves to the lower layer; upper layer:lower layer = 2:1, motor moves to the upper layer).

[0044] As shown in Figure 7, the results indicate that more rhodamine-labeled red fluorescent dual-drive liposome nanomotors were observed in high-density cell regions, thus demonstrating that the dual-drive liposome nanomotors actively target regions with higher cell density.

[0045] 8. Evaluation experiment on the anti-tumor effect of dual-power nanomotor.

[0046] The dual-powered liposome nanomotor obtained in Example 1 was co-incubated with breast cancer cells to verify its antitumor effect. Cytotoxicity was verified using a CCK-8 assay kit.

[0047] As shown in Figure 8, the results indicate that the tumor cell survival rate was 22.45% when the dual-powered liposome nanomotor was used in conjunction with gene-immunotherapy-photodynamic therapy. Furthermore, the killing effect of the dual-powered liposome nanomotor increased with increasing concentration, and the therapeutic effect was optimal when the dual-powered liposome nanomotor was used in conjunction with gene-immunotherapy-photodynamic therapy.

[0048] It should be noted that while the preferred embodiments of the present invention are given in the specification and accompanying drawings, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. These embodiments are not intended to impose additional limitations on the content of the present invention; their purpose is to provide a more thorough and comprehensive understanding of the disclosure of the present invention. Furthermore, the above-described technical features can be combined with each other to form various embodiments not listed above, all of which are considered to be within the scope of the present invention specification. Moreover, those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. A dual-drive liposome nanomotor, characterized in that, The invention comprises liposomes and metal nanoparticles, wherein the liposomes are loaded with IR808 and the metal nanoparticles have catalase-like activity, and the metal nanoparticles are encapsulated by the liposomes.

2. The dual-drive liposome nanomotor according to claim 1, characterized in that, The liposomes are DOPC liposomes.

3. The dual-powered liposome nanomotor according to claim 1, characterized in that, The metal nanoparticles are gold-manganese nanoparticles.

4. The dual-drive liposome nanomotor according to claim 1, characterized in that, The mass ratio of the metal nanoparticles to the liposomes is 8-11:

1.

5. The dual-drive liposome nanomotor according to any one of claims 1-4, characterized in that, It also includes DNAzyme, which is encapsulated in the liposome.

6. The dual-drive liposome nanomotor according to claim 5, characterized in that, The DNAzyme is a cholesterol-modified DNAzyme; the dual-powered liposome nanomotor has an asymmetric structure.

7. A method for preparing a dual-drive liposome nanomotor as described in any one of claims 1-6, characterized in that, Includes the following steps: (1) Prepare gold nanoparticles; (2) Mix the gold nanoparticles obtained in step (1) with potassium permanganate in a solution, and then add polycyclic aromatic hydrocarbons to the solution to react and obtain gold-manganese nanoparticles; (3) Load IR808 onto DOPC liposomes; (4) Mix the gold-manganese nanoparticles obtained in step (2) with the IR808-loaded DOPC liposomes obtained in step (3) in a certain proportion and incubate to obtain a gold-manganese liposome complex, wherein the mass ratio of the metal nanoparticles to the liposomes is 8-11:1; then add DNAzyme to the gold-manganese liposome complex solution for incubation to obtain a dual-power liposome nanomotor.

8. A method for preparing the dual-drive liposome nanomotor as described in claim 7, characterized in that, The mixing ratio of DNAzyme and manganese gold liposome complex in step (4) is as follows: 1 nM / L DNAzyme to 1-3 μg / mL manganese gold liposome complex.

9. The application of the dual-drive liposome nanomotor as described in any one of claims 1-6 in the treatment of tumors.

10. The application of the dual-drive liposome nanomotor according to claim 9 in the treatment of tumors, characterized in that, The tumor is breast cancer.

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