Ovarian cancer-targeted polymer nanoparticles, preparation method, and application thereof

Abstract

The present invention provides ovarian cancer-targeted polymer nanoparticles, their preparation method, and applications. The polymer nanoparticles have a core-shell structure, comprising a paclitaxel prodrug molecule core and an outer shell; the outer shell comprises a degradable polymer and a degradable polymer connected to a tumor target molecule at one end. The ovarian cancer-targeted polymer nanoparticles of the present invention are simple to prepare. The resulting ovarian cancer-targeted polymer nanoparticles exhibit long-term circulation stability, reduce drug distribution in normal tissues, and reduce drug toxicity and side effects. Compared to the clinical dosage form of paclitaxel, Taxol, the nanoparticles have improved anti-ovarian cancer activity at the cellular level.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials, and in particular relates to ovarian cancer-targeted polymer nanoparticles and a preparation method and application thereof. Background Art

[0002] Ovarian cancer is a common gynecological malignancy and the leading cause of cancer-related death among women worldwide. Due to its insidious onset and slow progression, most ovarian cancer patients are usually diagnosed in the late stage of the disease. To date, paclitaxel (PTX), a natural anticancer drug that acts by stabilizing microtubules, has been the first-line antitumor drug for the treatment of ovarian cancer for decades. However, due to disease resistance and recurrence, paclitaxel-based chemotherapy regimens have still failed to significantly improve the 5-year survival rate of ovarian cancer patients. In addition, severe side effects are another important issue with paclitaxel. In recent years, albumin-bound paclitaxel (Abraxane) has been used as a new formulation of paclitaxel for the safe treatment of patients with various types of tumors in clinical practice, but it still has disadvantages such as high cost and short in vivo half-life. In view of this, it is of great significance to seek new safe and effective treatments for ovarian cancer.

[0003] Nanodrug delivery systems can significantly enhance drug efficacy and reduce systemic toxicity by improving drug solubility and passively targeting tumors. Furthermore, due to their low immunogenicity, high biocompatibility, and biodegradability, nanodrug-based delivery strategies are gaining increasing attention in the field of biologics and clinical applications. For example, Genexol-PM is a polymeric nanoformulation that, in clinical practice, has been shown to increase drug delivery to tumors and be less toxic to patients compared to paclitaxel. However, since this drug is prepared by directly incorporating paclitaxel into a polymer carrier, it still has drawbacks in clinical applications, including premature release of the encapsulated drug and the inability to achieve active tumor-targeted delivery. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the first aspect of the present invention provides an ovarian cancer-targeted polymer nanoparticle that can target ovarian cancer and optimize drug efficacy while reducing adverse reactions.

[0005] The second aspect of the present invention provides a method for preparing the ovarian cancer-targeted polymer nanoparticles described in the first aspect.

[0006] The third aspect of the present invention provides the use of the ovarian cancer-targeted polymer nanoparticles described in the first aspect in the preparation of a drug for treating ovarian cancer with high CD44 expression.

[0007] According to the first aspect of the present invention, a polymer nanoparticle targeting ovarian cancer is proposed. The polymer nanoparticle has a core-shell structure, including a paclitaxel prodrug molecule core and an outer shell; the outer shell includes a degradable polymer and a degradable polymer with one end connected to a tumor target molecule.

[0008] In the present invention, the degradable polymer can prolong the circulation stability of the nanoparticles, while the tumor target molecule can give them targeted delivery to ovarian cancer with high CD44 expression and promote cell uptake of drugs, while reducing the distribution of drugs in normal tissues and reducing drug toxicity and side effects.

[0009] In some embodiments of the present invention, the polymer nanoparticles are spherical or quasi-spherical, and have an average particle size of 40 nm to 50 nm.

[0010] In some embodiments of the present invention, the paclitaxel prodrug molecule is prepared by covalently coupling polylactic acid and paclitaxel.

[0011] In the present invention, paclitaxel in the paclitaxel prodrug is covalently modified with polylactic acid so that it can be stably encapsulated by the encapsulating material, thereby avoiding premature release of drug molecules due to poor stability during in vivo application.

[0012] In some embodiments of the present invention, the loading amount of paclitaxel in the paclitaxel prodrug molecule is 5% to 10% of the total weight of the prodrug molecule.

[0013] In some embodiments of the present invention, the degradable polymer is selected from any one of polyethylene glycol-polylactic acid, polyethylene glycol-polycaprolactone, polyethylene glycol-polyglutamic acid, and polyethylene glycol-chitosan.

[0014] In some embodiments of the present invention, the tumor target molecule is capable of binding to the CD44 molecule.

[0015] In some preferred embodiments of the present invention, the tumor target molecule is selected from any one of hyaluronic acid, RP-1 polypeptide, and A6 short peptide, preferably hyaluronic acid.

[0016] In this invention, hyaluronic acid (HA) is a hydrophilic polymer that binds to the CD44 receptor, a transmembrane glycoprotein highly expressed in various malignancies, including ovarian cancer. Surface modification of polymer nanoparticles with HA will help improve targeted drug delivery to ovarian cancer, optimizing drug efficacy while minimizing adverse reactions.

[0017] According to a second aspect of the present invention, a method for preparing the ovarian cancer-targeting polymer nanoparticles according to the first aspect is provided, comprising the following steps:

[0018] A degradable polymer, a degradable polymer with one end connected to a tumor target molecule, and a paclitaxel prodrug molecule are mixed with an organic solvent, added dropwise into water, stirred, and dialyzed to obtain the ovarian cancer-targeted polymer nanoparticles.

[0019] In some embodiments of the present invention, the mass ratio of the degradable polymer, the degradable polymer having one end connected to a tumor target molecule, and the paclitaxel in the paclitaxel prodrug molecule is (4.5-9.5):(4.5-9.5):1.

[0020] In some embodiments of the present invention, the organic solution is any one of acetone, ethanol, and isopropanol.

[0021] In some embodiments of the present invention, the water is any one of double distilled water, deionized water, and ultrapure water.

[0022] In some preferred embodiments of the present invention, the stirring time is 20 min to 40 min.

[0023] In some preferred embodiments of the present invention, the stirring further comprises removing the organic solvent by rotary evaporation, and the temperature of the rotary evaporation is 45°C to 55°C.

[0024] In some preferred embodiments of the present invention, the molecular weight cut-off of the dialysis is 5 kDa to 10 kDa.

[0025] In some more preferred embodiments of the present invention, the dialysis further comprises washing the concentrated retentate with an ultrafiltration tube.

[0026] The third aspect of the present invention provides the use of the ovarian cancer-targeted polymer nanoparticles described in the first aspect in the preparation of a drug for treating ovarian cancer with high CD44 expression.

[0027] The beneficial effects of the present invention are:

[0028] The polymer nanoparticles of the present invention exhibit long-term circulation stability, reduce drug distribution in normal tissues, and mitigate drug toxicity and side effects. Compared to the clinical dosage form of paclitaxel, Taxol, they also exhibit improved anti-ovarian cancer activity at the cellular level. Furthermore, because the present invention utilizes a paclitaxel prodrug, in which the paclitaxel is covalently modified with polylactic acid, it can be stably entrapped in the encapsulating material, further preventing premature release of the paclitaxel drug molecule due to poor stability during in vivo use.

[0029] The preparation method of the polymer nanoparticles of the present invention is simple, the raw materials are readily available, and large-scale production is possible. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The present invention will be further described below with reference to the accompanying drawings and embodiments, in which:

[0031] Figure 1 Figures A and B are the particle size distribution and electron microscopy results of the polymer nanoparticles prepared in Example 1 and the comparative example of the present invention; Figures A and B are the particle size distributions of the polymer nanoparticles (PLA-PTX NPs) prepared in the comparative example and the polymer nanoparticles (HA-PLA-PTX NPs) prepared in Example 1 measured by DLS, respectively; Figures C and D are electron microscopy images of PLA-PTX NPs and HA-PLA-PTX NPs, respectively.

[0032] Figure 2 The particle size and polydispersity index (PDI) of the polymer nanoparticles prepared in Example 1 (HA-PLA-PTX NPs) of the present invention and the comparative example (PLA-PTX NPs) were respectively detected using a nanoparticle size analyzer at different time points.

[0033] Figure 3 Figure 3 shows the inhibitory effects of the clinical dosage form paclitaxel (Taxol), the polymer nanoparticles prepared in the comparative example of the present invention (PLA-PTXNPs), and the polymer nanoparticles prepared in Example 1 (HA-PLA-PTX NPs) on ovarian cancer cell lines with different CD44 expression levels; A shows the proliferation inhibition effect on the CD44 low-expressing cell line A2780; B shows the proliferation inhibition effect on the CD44 high-expressing cell line SKOV3.

[0034] Figure 4 Figure 1 shows the uptake of the polymer nanoparticles prepared in Example 1 of the present invention in human ovarian cancer cells A2780 and human ovarian adenocarcinoma cells SKOV3; A is a fluorescence microscopic image of the polymer nanoparticles prepared in Example 1 after incubation with A2780 cells for 1 and 4 hours; B is a fluorescence microscopic image of the polymer nanoparticles prepared in Example 1 after incubation with SKOV3 cells for 1 and 4 hours; C is the flow cytometry detection result of the polymer nanoparticles prepared in Example 1 after incubation with A2780 cells for 1 and 4 hours; D is the flow cytometry detection result of the polymer nanoparticles prepared in Example 1 after incubation with SKOV3 cells for 1 and 4 hours.

[0035] Figure 5 Figures 20 and 21 show the effects of the polymer nanoparticles prepared in Example 1 and the comparative example of the present invention on the proliferation function of ovarian cancer cells SKOV3. Figures A and B are cell proliferation images and statistical graphs of SKOV3 cells after treatment with the nanoparticles of Example 1 and the comparative example for 24 hours, respectively. Figures C and D are cell apoptosis and statistical graphs of SKOV3 cells after treatment with the nanoparticles of Example 1 and the comparative example for 24 hours, respectively. * indicates P < 0.5, ** indicates P < 0.01, and *** indicates P < 0.001. DETAILED DESCRIPTION

[0036] The following will clearly and completely describe the concept and technical effects of the present invention in conjunction with the embodiments to fully understand the purpose, features and effects of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0037] The paclitaxel prodrug molecules in the following examples and comparative examples were synthesized using the method described in the disclosed invention patent CN109562187A, specifically referring to paragraphs

[0028] ,

[0033] , and

[0038] -

[0039] of the specification.

[0038] Example 1

[0039] This example prepares ovarian cancer-targeted polymer nanoparticles, and the specific process is as follows:

[0040] 9.5 mg of polyethylene glycol-polylactic acid, 9.5 mg of polylactic acid-polyethylene glycol-hyaluronic acid, and 1 mg of paclitaxel-equivalent paclitaxel prodrug molecules were accurately weighed and thoroughly dissolved and dispersed in 2 mL of acetone. The mixture was then slowly added dropwise to 10 mL of double-distilled water and stirred at room temperature for 30 minutes. The organic solvent was then removed by rotary evaporation in a 45°C–55°C water bath. The solution was then dialyzed overnight against pure water using a 10 kDa dialysis membrane, with the water frequently replaced, to remove free encapsulating material. Finally, the solution was concentrated using an Amicon Ultra-4 (10k MWCO, Millipore Corp.) ultrafiltration tube to obtain the ovarian cancer-targeted polymer nanoparticles (abbreviated as HA-PLA-PTX NPs).

[0041] Example 2

[0042] This example prepares ovarian cancer-targeted polymer nanoparticles, and the specific process is as follows:

[0043] 4.5 mg of polyethylene glycol-polylactic acid, 4.5 mg of polylactic acid-polyethylene glycol-hyaluronic acid, and 1 mg of paclitaxel-equivalent paclitaxel prodrug molecules were accurately weighed and thoroughly dissolved and dispersed in 2 mL of acetone. The mixture was then slowly added dropwise to 10 mL of double-distilled water and stirred at room temperature for 30 minutes. Subsequently, the organic solvent was removed by rotary evaporation in a water bath at 45°C to 55°C. The solution was then dialyzed overnight against pure water using a 10 kDa dialysis membrane, with the water frequently replaced, to remove free encapsulating material. Finally, the solution was concentrated using an Amicon Ultra-4 (10k MWCO, Millipore Corp.) ultrafiltration tube to obtain the ovarian cancer-targeted polymer nanoparticles (abbreviated as HA-PLA-PTX NPs).

[0044] Example 3

[0045] This example prepares ovarian cancer-targeted polymer nanoparticles, and the specific process is as follows:

[0046] 9.5 mg of polyethylene glycol-polylactic acid, 9.5 mg of polylactic acid-polyethylene glycol-hyaluronic acid, and 1 mg of paclitaxel-equivalent paclitaxel prodrug molecules were accurately weighed and thoroughly dissolved and dispersed in 2 mL of ethanol. The mixture was then slowly added dropwise to 10 mL of double-distilled water and stirred at room temperature for 30 minutes. The organic solvent was then removed by rotary evaporation in a 45°C–55°C water bath. The solution was then dialyzed overnight against pure water using a 10 kDa dialysis membrane, with the water frequently replaced, to remove free encapsulating material. Finally, the solution was concentrated using an Amicon Ultra-4 (10k MWCO, Millipore Corp.) ultrafiltration tube to obtain the ovarian cancer-targeted polymer nanoparticles (abbreviated as HA-PLA-PTX NPs).

[0047] Comparative Example

[0048] This comparative example prepares a polymer nanoparticle. The main difference from Example 1 is that one end of the polylactic acid-polyethylene glycol is not connected to hyaluronic acid. The specific process is as follows:

[0049] 19 mg of polyethylene glycol-polylactic acid and 1 mg of paclitaxel-equivalent paclitaxel prodrug molecules were accurately weighed and thoroughly dissolved and dispersed in 2 mL of acetone. The mixture was then slowly added dropwise to 10 mL of double-distilled water and stirred at room temperature for 30 minutes. Subsequently, the organic solvent was removed by rotary evaporation in a water bath at 45°C to 55°C. The solution was then dialyzed overnight against pure water using a 10 kDa dialysis membrane, with the water frequently replaced, to remove free encapsulating material. Finally, the solution was concentrated using an Amicon Ultra-4 (10k MWCO, Millipore Corp.) ultrafiltration tube to obtain the polymer nanoparticles (abbreviated as PLA-PTX NPs).

[0050] Test example

[0051] 1. The morphology and particle size distribution of the polymer nanoparticles prepared in Example 1 and the comparative example were detected by nanoparticle size analyzer and transmission scanning electron microscope respectively. Figure 1 , wherein A and B are the particle size distributions of the non-targeted polymer nanoparticles (PLA-PTX NPs) prepared in the comparative example and the targeted polymer nanoparticles (HA-PLA-PTX NPs) prepared in Example 1, respectively, obtained by DLS measurement; Figures C and D are electron microscope scanning images of PLA-PTX NPs and HA-PLA-PTX NPs, respectively.

[0052] from Figure 1As can be seen from A and B, both non-targeted polymer nanoparticles (PLA-PTX NPs) and targeted polymer nanoparticles (HA-PLA-PTX NPs) have good hydrated particle sizes, both of which are below 50 nm. They have the ability to accumulate in tumor sites through the enhanced permeability and retention (EPR) effect in vivo. At the same time, both nanoparticles have good polydispersity, as their polydispersity index (PDI) is less than 0.2. Figure 1 As can be seen in Figures C and D, PLA-PTX NPs and HA-PLA-PTX NPs exhibit spherical morphology, proving the successful preparation of nanoparticles.

[0053] 2. The particle size and polydispersity index (PDI) of PLA-PTX NPs and HA-PLA-PTX NPs were measured by nanoparticle size analyzer at different time points (0h, 2h, 4h, 8h, 12h, 24h, 48h, 96h). The results are shown in Figure 2 .

[0054] from Figure 2 It can be seen that as time goes by, the particle size and PDI of the two nanoparticles do not show obvious changes, indicating that the polylactic acid-modified paclitaxel prodrug molecules can be more stably encapsulated and stored after being prepared into nanoparticles, and have good stability, thus laying the foundation for the storage and transportation of drugs in clinical use.

[0055] 3. Cell viability experiments were performed to evaluate the killing potential of different polymer nanoparticles on ovarian cancer cells with different CD44 expression levels. CD44 high-expressing ovarian cancer SKOV3 cells and CD44 low-expressing ovarian cancer A2780 cells were cultured at a rate of 5×10 3 The cells were seeded into 96-well culture plates at a density of 1000 μg / well and then incubated overnight at 37°C in a culture medium containing 5% FBS. Subsequently, the cells were treated with different concentrations of Taxol (clinical formulation of paclitaxel), PLA-PTX NPs and HA-PLA-PTX NPs for 72 hours. After the time point, the culture medium in each well was replaced with 200 μL fresh culture medium containing 20 μL CCK-8 detection reagent, and the cells were cultured at 37°C for 2 hours. The absorbance of each well was detected at a wavelength of 450 nm using an enzyme reader, and the survival rate was converted into GraphpadPrism 8.0 to fit the half-inhibitory concentration (IC50) of each therapeutic drug. 50 ), the results are shown in Table 1 and Figure 3 .

[0056] Table 1 IC values of Taxol, PLA-PTX NPs, and HA-PLA-PTX NPs on CD44-low-expressing ovarian cancer cells A2780 and CD44-high-expressing ovarian cancer cells SKOV3 50 value

[0057]

[0058] As shown in Table 1, the IC values of HA-PLA-PTX NPs in CD44-highly expressed ovarian cancer cells SKOV3 are 50 The IC of PLA-PTX NPs was 12.44±0.85nmol / L. 50 was 23.52±1.04nmol / L, and the difference between the two was significant. In ovarian cancer cells A2780 with low CD44 expression, the IC 50 The IC of PLA-PTX NPs was 96.51±3.90nmol / L. 50 was 100.50 ± 3.54 nmol / L, and the two values were similar ( Table 1 ); Figure 3 The results more intuitively show the inhibitory effects of Taxol, PLA-PTX NPs, and HA-PLA-PTX NPs on ovarian cancer cell lines with different CD44 expression levels. The above results indicate that HA-PLA-PTX NPs have relatively higher anti-tumor activity against ovarian cancer cells with high CD44 expression.

[0059] 4. Uptake of polymer nanoparticles by cancer cells

[0060] First, polymer nanoparticles were labeled with Nile red (NR) to reflect the uptake of nanoparticles by cells. A2780 and SKOV3 cells were cultured at 8×10 4 Cells were seeded at a density of 100 cells / well on confocal microplates and incubated at 37°C for 24 hours. The cells were then treated with 20 nM HA-PLA-PTX NPs containing 0.5 μM Nile Red for 1 hour and 4 hours, respectively. Cell nuclei were then stained with Hoechst 33342 for 15 minutes at 37°C. After rinsing twice with cold PBS, nanoparticle uptake by the different cells was assessed using confocal fluorescence microscopy and flow cytometry.

[0061] The uptake of the polymer nanoparticles prepared in Example 1 in human ovarian cancer cells A2780 and human ovarian adenocarcinoma cells SKOV3 was determined by fluorescence labeling technology. Figure 4 As shown in the figures, Figure A shows the fluorescence microscopic images of Nile red (NR)-labeled polymer nanoparticles (HA-PLA-PTX NPs) incubated with A2780 cells for 1h and 4h; Figure B shows the fluorescence microscopic images of Nile red (NR)-labeled polymer nanoparticles incubated with SKOV3 cells for 1h and 4h; Figures C and D are the uptake of Nile red-labeled HA-PLA-PTX NPs by A2780 and SKOV3 cells measured by flow cytometry, respectively.

[0062] from Figure 4 As can be seen, the fluorescence intensity in both cell lines gradually increased with increasing incubation time. Notably, after 4 hours, the fluorescence intensity detected in SKOV3 was significantly higher than that in A2780. Flow cytometry was used to examine the fluorescence signals within each cell line after 1 and 4 hours of incubation. The results showed that the average fluorescence intensity measured by flow cytometry after 4 hours of incubation was consistent with the fluorescence imaging results, indicating that hyaluronic acid-modified nanoparticles are more effective in delivering drugs to ovarian cancer cells with high CD44 expression.

[0063] 5. Effects of polymer nanoparticles on ovarian cancer cell function

[0064] The 5-ethynyl-2-deoxyuridine (EdU) proliferation assay was used to quantify the proliferation of cells after treatment with different drugs. 4 Each well was treated with Taxol, PLA-PTX NPs, and HA-PLA-PTX NPs containing an equivalent concentration of 20 nM paclitaxel for 24 hours, followed by the addition of 0.1 mL of EdU reagent to each well and further incubation at 37 ° C for 2 hours. Next, the cells were fixed for 30 minutes at room temperature using PBS containing 4% paraformaldehyde and then incubated with a solution containing Hoechst 33342 for another 30 minutes to label the cell nuclei. The stained cells were observed using a fluorescence microscope, and photographs of 5 fields of view were randomly taken using a fluorescence microscope. Image J software was used to count the total number of cells and the number of actively proliferating cells, and the cell proliferation rate was then calculated.

[0065] The effects of the polymer nanoparticles prepared in Example 1 and the comparative example on the proliferation of ovarian cancer cells SKOV3 were evaluated by EdU cell proliferation experiments. Figure 5 Figures A and B show cell proliferation after 24 hours of treatment with 20 nmol / L HA-PLA-PTX NPs and PLA-PTX NPs, respectively. The results showed that the cell proliferation rates after treatment with HA-PLA-PTX NPs and PLA-PTX NPs were 28.83% and 34.63%, respectively, significantly lower than the 41.63% in the control group. Furthermore, SKOV3 cells treated with HA-PLA-PTX NPs exhibited an even lower proliferation rate, indicating that CD44 targeting can impart stronger tumor inhibition capabilities to the nanoparticles.

[0066] Annexin V / PI double staining was used to detect the apoptosis of SKOV3 cells after drug treatment. 5Cells were seeded onto 6-well plates (cells / well) and then incubated overnight at 37°C to promote adhesion. After treating the cells with Taxol, PLA-PTX NPs, or HA-PLA-PTX NPs containing an equivalent concentration of 20 nM paclitaxel for 24 hours, the cells were trypsinized and collected by centrifugation. Subsequently, the cells were washed with PBS and resuspended in 500 μL of binding buffer containing 5 μL Annexin V-FITC and 5 μl PI, and the system was incubated at room temperature in the dark for half an hour. Finally, flow cytometry was used to examine the cells that had been double-labeled with Annexin V / PI.

[0067] The results are as follows Figure 5 As shown in C and D, the cell apoptosis of the SKOV3 cell line treated with HA-PLA-PTX NPs for 24 hours was 6.08 times that of the control group, while the apoptosis of the PLA-PTX NPs-treated group was only 3.76 times that of the control group, indicating that HA-PLA-PTX NPs has a stronger killing effect on CD44-positive ovarian cancer.

[0068] While the embodiments of the present invention have been described in detail above, the present invention is not limited to the embodiments described above. Various modifications may be made within the scope of knowledge possessed by a person skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof may be combined with one another unless there is a conflict.

Claims

1. An ovarian cancer-targeted polymer nanoparticle, characterized in that: The polymer nanoparticles are of a core-shell structure, comprising a paclitaxel prodrug molecule core and an outer shell; the outer shell comprises a degradable polymer and a degradable polymer connected to a tumor target molecule at one end; the paclitaxel prodrug molecule is prepared by covalently coupling polylactic acid and paclitaxel; the degradable polymer is polyethylene glycol-polylactic acid; and the degradable polymer connected to a tumor target molecule at one end is polylactic acid-polyethylene glycol-hyaluronic acid; The ovarian cancer-targeted polymer nanoparticles are prepared by the following steps: mixing a degradable polymer, a degradable polymer with a tumor target molecule attached at one end, and a paclitaxel prodrug molecule with an organic solvent, adding the mixture dropwise to water, stirring, dialyzing, and washing the concentrated retentate with an ultrafiltration tube after dialysis to obtain the ovarian cancer-targeted polymer nanoparticles; The mass ratio of the degradable polymer, the degradable polymer connected to the tumor target molecule at one end, and the paclitaxel in the paclitaxel prodrug molecule is (4.5-9.5):(4.5-9.5):

1.

2. The polymer nanoparticles according to claim 1, characterized in that The loading amount of paclitaxel in the paclitaxel prodrug molecule is 5% to 10% of the total weight of the prodrug molecule.

3. The method for preparing ovarian cancer-targeting polymer nanoparticles according to any one of claims 1 to 2, characterized in that: A degradable polymer, a degradable polymer with one end connected to a tumor target molecule, and a paclitaxel prodrug molecule are mixed with an organic solvent, added dropwise to water, stirred, and dialyzed to obtain the ovarian cancer-targeted polymer nanoparticles; the mass ratio of the degradable polymer, the degradable polymer with one end connected to a tumor target molecule, and the paclitaxel in the paclitaxel prodrug molecule is (4.5-9.5):(4.5-9.5):

1.

4. The preparation method according to claim 3, characterized in that The molecular weight cut-off of the dialysis is 5 kDa to 10 kDa.

5. Use of the ovarian cancer-targeted polymer nanoparticles according to any one of claims 1 to 2 in the preparation of a drug for treating ovarian cancer with high CD44 expression.

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