A fluorinated polymer-based nanocarrier and a preparation method and application thereof

Abstract

The application discloses a kind of nanocarrier based on fluorinated polymer and its preparation method and application;The method comprises: (1) synthesis compound I;(2) synthesis compound II;(3) with compound I and compound II as raw material, by fluorine-fluorine interaction, obtain compound III;(4) drop compound III into water, obtain fluorinated polymer carrier;(5) nucleic acid (such as DNA or RNA) or protein solution and fluorinated polymer carrier solution are mixed sufficiently, obtain gene-loaded polymer nanosystem.The method can assemble chemotherapeutic drugs such as adriamycin and other chemotherapeutic drugs with hydrophilic polyethylene glycol, and package biomolecules such as nucleic acid drugs, such as small interfering RNA with the function of down-regulating TOX protein, to construct high drug-loading gene co-delivery system of chemotherapeutic drug, for solid tumor antitumor immunotherapy.

Description

Technical Field

[0001] This invention relates to the field of carrier preparation technology for the combined delivery of chemical drugs and gene drugs, and particularly to a fluorinated polymer-based nanocarrier, its preparation method, and its application. Background Technology

[0002] Improving the water solubility of chemical drugs using polymer nanoparticles has been widely applied in drug delivery systems. Nanoparticles often form a core-shell structure through coupling between a carrier and the drug, utilizing hydrophobic interactions to encapsulate hydrophobic drugs within the core, while the hydrophilic shell provides targeting, masking, and enhanced circulation functions. However, non-specific hydrophobic interactions between drug molecules can lead to drug aggregation during polymer nanoparticle formation, resulting in reduced drug loading and uniformity. Therefore, designing more effective prodrug strategies to achieve higher drug loading in chemical drug delivery systems is crucial for constructing polymer nanoparticles.

[0003] Compared to hydrogen, fluorine molecules exhibit a fluorinophilic effect, avoiding interactions with other groups. Furthermore, fluorinated carbon chains are both hydrophobic and oleophobic, exhibiting high phase segregation in aqueous biological environments and lipid bilayers. These properties are beneficial for increasing polymer cycling stability and tissue permeability. Therefore, utilizing stronger and more specific fluorine-fluorine interactions holds promise for achieving more efficient carrier and drug coupling and assembly. In addition, fluorinated polymers with low surface energy can interact even at low concentrations, further highlighting the practicality of fluorine-fluorine interactions.

[0004] Breast cancer and melanoma are very common cancers among current cancer patients. Treating these, and not limited to, solid tumor cancers with anti-tumor immunotherapy holds promise for killing solid tumor tissue and easily metastatic cancer cells with greater safety. Doxorubicin (DOX), a classic anti-tumor drug, not only directly kills cells by damaging DNA, but also triggers cell damage-related molecular patterns leading to immunogenic cell death (ICD), thereby stimulating the maturation of dendritic cells (DCs) and promoting the infiltration of effector T cells. However, in the treatment of solid tumors, the tumor microenvironment can hinder anti-tumor immunotherapy through various regulatory mechanisms, inducing increased expression of co-inhibitory receptors on T cells exposed to the tumor microenvironment, decreased proliferation capacity, and decreased production of type I immune cytokines. This state of T cell exhaustion hinders the anti-tumor immunotherapy effect of chemotherapy drugs. Therefore, it is necessary to study a nanoparticle that can deliver the chemotherapy drug doxorubicin while regulating immune cells in the tumor microenvironment to achieve efficient anti-tumor immunotherapy. Thymocyte selection-associated high-mobility group box protein (TOX) is significantly upregulated in exhausted T cells. Downregulating TOX expression levels via small interfering RNA may restore the anti-tumor ability of T cells and improve the efficiency of doxorubicin immunogenic chemotherapy. Summary of the Invention

[0005] This invention provides a fluorinated polymer-based nanocarrier, its preparation method, and its application. This method enables the assembly of chemotherapeutic drugs such as doxorubicin with hydrophilic polyethylene glycol and the encapsulation of biomolecules such as small interfering RNA (siTOX) that downregulates TOX protein function, thereby constructing a high-drug-load chemical drug gene co-delivery system for anti-tumor immunotherapy of human solid tumor cancer.

[0006] In a first aspect, the present invention provides a method for preparing a nanocarrier based on a fluorinated polymer, comprising the following steps:

[0007] (1) Using 2,2,3,3,4,4,5,5,6,6,7,7-dodecano-1,8-octanediol, oxaloyl chloride and polyethylene glycol as raw materials, the mixture was polymerized, dialyzed and freeze-dried to obtain compound I;

[0008]

[0009] (2) Using 3,5-bis(trifluoromethyl)benzaldehyde and doxorubicin as raw materials, compound II was obtained through Schiff base formation reaction;

[0010]

[0011] (3) Using the compounds I and II as raw materials, a fluorine-fluorine interaction occurs in a dimethyl sulfoxide solvent to obtain a fluorinated polyethylene glycol-fluorinated doxorubicin polymer;

[0012] (4) Add the fluorinated polyethylene glycol-fluorinated doxorubicin polymer obtained in step (3) to water, dialyze, freeze dry, and obtain a nanocarrier based on the fluorinated polymer.

[0013] Further, in step (1), the polymerization reaction time is 0.5 h–60 h, preferably 6 h. The molar ratio of 2,2,3,3,4,4,5,5,6,6,7,7-dodecano-1,8-octanediol, oxaloyl chloride, and polyethylene glycol is 1:(1-15):1, preferably 1:(1-3):1, more preferably 1:2:1. The reaction temperature range is 0–99 °C, preferably 25 °C; the molecular weight of the polyethylene glycol is 100-10000, preferably 600.

[0014] Furthermore, in step (2), the reaction time is 0.5 h–240 h, preferably 24 h. The molar ratio of 3,5-bis(trifluoromethyl)benzaldehyde to doxorubicin is 0.1–10:1, preferably 1–2:1, more preferably 1.1:1. The reaction temperature range is 0–99 °C, preferably 25 °C.

[0015] Furthermore, in step (3), the reaction time is 0.5h–24h, preferably 1h. The reaction temperature range is 0–99℃, preferably 25℃.

[0016] Furthermore, in step (3), the mass ratio of compound I to compound II is 0.01–100, preferably 1.

[0017] Furthermore, in step (4), the stirring is continued for 0.5h–24h during the dropwise addition process, preferably 1h. The dropwise addition concentration range is 0.1–10mg / mL, preferably 1mg / mL.

[0018] Secondly, the present invention provides a fluorinated polymer-based nanocarrier prepared by the above method.

[0019] Thirdly, the present invention also provides a fluorinated polymer nanoparticle system for carrying gene drugs, the preparation method of which is as follows: after dissolving the nucleic acid drug, it is thoroughly mixed with the aforementioned fluorinated polymer-based nanocarrier in water, the mass ratio of the nucleic acid drug to the fluorinated polymer nanocarrier is 1:0.01-100, and after standing, the gene-carrying polymer nanosystem is obtained.

[0020] Furthermore, the settling time is 5 min–24 h, preferably 20 min.

[0021] Fourthly, the present invention also provides the application of the fluorinated polymer-based nanocarrier or the fluorinated polymer nanoparticle system for carrying gene drugs in the preparation of drugs for treating human solid tumor cancer.

[0022] Furthermore, solid tumors in humans include breast cancer or melanoma.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The present invention uses fluorinated polyethylene glycol as raw material to synthesize products. Polyethylene glycol is a polymer molecule with good biocompatibility, and fluorine is present in 30% of marketed drugs. Fluorinated polyethylene glycol is safe to use as a drug in clinical treatment.

[0025] (2) This invention relies on the interaction between the fluorinated carrier and the drug. The synthesis process is simple, and the strategy of loading the modified carrier into nanoparticles has the potential to be widely applied to chemotherapy drugs.

[0026] (3) The nanoparticles formed in this invention have a high permeability and long retention effect, which can increase the concentration of drugs in solid tumor tissues, reduce the side effects of chemical drugs, and have a high drug loading capacity for chemical drugs, thereby improving treatment efficiency.

[0027] (4) In this invention, chemotherapy drugs and gene drugs are delivered together. The combined effect of the two promotes the activation of immune cells in the tumor microenvironment and exhibits anti-tumor immune effects against solid tumors. Attached Figure Description

[0028] Figure 1 This is a schematic diagram illustrating the principle of the present invention in exerting anti-tumor immune effects through the combined delivery of chemical drugs and gene drugs.

[0029] Figure 2 To characterize the loading capacity and physical properties of the polymer nanoparticles formed in Example 1;

[0030] Among them, A. Agarose gel electrophoresis was used to detect gene condensation at different mass ratios (w / w); B. The particle size change of gene-loaded fluorinated polymer nanoparticles over 48 h in PBS solution at pH 7.4 or 10% serum solution; C. The particle size change of gene-loaded fluorinated polymer nanoparticles over 12 h in solutions with different pH and different hydrogen peroxide concentrations; D. DOX release from nanoparticles under different conditions.

[0031] Figure 3 This describes the induction of ICD in tumor cells by polymer nanoparticles in Example 1, as well as their ability to promote the maturation of dendritic cells.

[0032] Among them, A. Apoptosis level of mouse breast cancer (4T1) cells after different treatments with different concentrations, PBS was the phosphate buffered control group, fPEG was fluorinated polyethylene glycol, DOX was free doxorubicin, and fPEG-fDOX@siTOX was siTOX-loaded fluorinated polymer nanoparticles; BD. Exposure of calreticulin (CRT) in tumor cells under different conditions, and secretion levels of adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1); E. Maturation level of DC cells under different conditions.

[0033] Figure 4 This describes the in vivo immune activation of 4T1 tumor-bearing mice by the polymer nanoparticles in Example 1.

[0034] Among them, A. DC cell maturation level in tumor-bearing mice after administration of different drugs; B. CD8 cell maturation level in tumor-bearing mice after administration of different drugs. + C. T cell infiltration into tumor tissue; D. Levels of exhausted T cells in tumor tissues of mice treated with different drugs; E. Analysis of CD8 infiltrating tumor tissues by flow cytometry. + TOX content in T cells.

[0035] Figure 5 This demonstrates the antitumor and antimetastatic effects of the polymer nanoparticles in Example 1 on 4T1 tumor-bearing mice.

[0036] Among them, A. Changes in solid tumor volume in tumor-bearing mice after various treatments, NS is the blank control group injected with physiological saline, DOX is injected with free doxorubicin, fPEG-fDOX@siNC is injected with fluorinated polymer nanoparticles carrying siRNA (siNC) without therapeutic effect, and fPEG-fDOX@siTOX is injected with fluorinated polymer nanoparticles carrying siTOX; B. Tumor weight of mice after different treatments at the end of the experimental observation; C. Relative body weight changes of tumor-bearing mice during treatment; D. Survival status of tumor-bearing mice under different treatments within 60 days; E. Lung tissue and H&E staining images of lung tissue in each group of mice in the anti-metastasis study.

[0037] Figure 6 This study demonstrates the antitumor and antimetastatic effects of the polymer nanoparticles in Example 1 on tumor-bearing mice inoculated with mouse melanoma (B16F10) cells.

[0038] Among them, A. Changes in solid tumor volume in C57BL / 6 tumor-bearing mice after various treatments; B. Tumor weight of mice with different drug administrations at the end of the experimental observation; C. Tumor tissue images of tumor-bearing mice; D. Survival status of tumor-bearing mice with different treatments within 60 days; E. Lung tissue and H&E staining images of lung tissue of mice in each group in the anti-metastasis study. Detailed Implementation

[0039] The following embodiments provide a better understanding of the present invention, but are not limited to it. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods.

[0040] Example 1: Preparation of Fluorinated Polymer Nanoparticles Using Fluorofluorine Interactions

[0041] (1) 2,2,3,3,4,4,5,5,6,6,7,7-dodecano-1,8-octanediol (MW = 362.11, 713 mg, 2.0 mmol) was dissolved in 5 mL of dimethylformamide, oxaloyl chloride (MW = 126.92, 500 mg, 4.0 mmol) and polyethylene glycol (MW ≈ 600, 1.18 g, 2.0 mmol) were dissolved in 5 mL of dichloromethane and added dropwise to the aforementioned dimethylformamide solution at 4°C. The reaction was carried out at room temperature for 6 hours under nitrogen protection, purified by dialysis for 48 hours, and freeze-dried for 24 hours to obtain fluorinated polyethylene glycol; the reaction formula is as follows:

[0042]

[0043] (2) 3,5-bis(trifluoromethylbenzaldehyde) (MW = 242.11, 484 mg, 2.0 mmol) and free doxorubicin (MW = 543.52, 1.09 g, 2.0 mmol) were dissolved in 10 mL of dimethyl sulfoxide solution, a trace amount of acetic acid was added, and the reaction was carried out under nitrogen protection for 24 hours. The product was purified by column chromatography (dichloromethane:methanol = 10:1) to obtain fluorinated doxorubicin. The reaction formula is as follows:

[0044]

[0045] (3) The fluorinated polyethylene glycol (MW = 3963, 198 mg, 0.05 mmol) obtained in step (1) and the fluorinated doxorubicin (MW = 767.64, 198 mg, 0.25 mmol) obtained in step (2) were dissolved in 1 mL of dimethyl sulfoxide solution and stirred at room temperature for 1 hour in the dark. After stirring was stopped, it was added dropwise to phosphate buffer and stirred for another hour. The mixture was purified by dialysis for 48 hours and then freeze-dried for 24 hours to obtain the fluorinated polyethylene glycol-fluorinated doxorubicin polymer. It was dissolved in aqueous solution at a concentration of 0.2–2 times the gene mass and mixed with siNC solution or siTOX solution to obtain siNC-loaded fluorinated polymer nanoparticles and siTOX-loaded fluorinated polymer nanoparticles with different w / w ratios.

[0046] Example 2: Physical Property Study

[0047] The fluorinated polymer nanoparticles prepared in Example 1 were used to study the physical properties of the nanoparticles under different treatments.

[0048] The specific research methods are as follows:

[0049] Experiment (1): Fluorinated polymer nanoparticle solutions with different w / w ratios were allowed to stand for 30 minutes, and then electrophoresis was performed at 100V for 15 minutes to verify the encapsulation of genes in nanoparticles and to image the results using an imaging system.

[0050] Experiment (2): The particle size of siNC fluorinated polymer nanoparticles was detected after incubation in PBS buffer at pH 7.4 or 10% serum (FBS) for 0.5, 2, 6, 12 and 24 hours; the particle size of nanoparticles was measured after incubation in PBS buffer at pH 5.0 and in PBS buffer at pH 7.4 and pH 5.0 containing 100 μM hydrogen peroxide for 0.5, 4, 8 and 12 hours.

[0051] Experiment (3): Dialysis bags (MWCO, 1000 Da) containing nanoparticles were placed in PBS buffers under different conditions. Samples were continuously collected from the buffers over 48 hours with stirring at 300 rpm. The free doxorubicin released from the nanoparticles was measured at 480 nm using a UV spectrophotometer.

[0052] The measurement results are as follows Figure 2 As shown, electrophoresis results indicate that the fluorinated polyethylene glycol-fluorinated doxorubicin polymer enhances gene loading capacity compared to free doxorubicin. Continuous particle size monitoring in serum-containing solutions demonstrates the stability of the fluorinated polymer nanoparticles in 10% serum solution. Particle size results and doxorubicin release results under different pH and hydrogen peroxide conditions indicate that the fluorinated polymer nanoparticles possess the ability to release the drug sensitively under acidic and oxidizing conditions.

[0053] Example 3: The siTOX-loaded fluorinated polymer nanoparticles prepared in Example 1 were used as controls to study the apoptosis, immunogenic death, and induction of DC cell maturation in mouse breast cancer cells.

[0054] The specific method is as follows:

[0055] Experiment (1): Fluorinated polyethylene glycol, free doxorubicin and siTOX-loaded fluorinated polymer nanoparticles (2.5 μg / mL siTOX) were prepared at a concentration of 5 μg / mL. Apoptosis was analyzed by flow cytometry using an apoptosis detection kit.

[0056] Experiment (2): Four groups of 4T1 cells were treated with free doxorubicin containing 1 μg / mL doxorubicin, siTOX-loaded fluorinated polymer nanoparticles (0.5 μg / mL siTOX), PBS buffer, and fluorinated polyethylene glycol, respectively. After 24 hours, the supernatant was removed, and the changes at the three molecular levels were detected by CRT antibody, ATP kit, and HMGB1 enzyme-linked immunosorbent assay kit, respectively.

[0057] Experiment (3): Four groups of 4T1 cells were treated as described in (2). After 12 hours, the supernatant was removed, and DC 2.4 cells were added to the 4T1 cells and cultured for 12 hours. The maturation of DC cells was detected by flow cytometry using fluorescent antibodies against CD11c, CD80 and CD86.

[0058] The measurement results are as follows Figure 3 As shown, the apoptosis results indicate that the siTOX-loaded fluorinated polymer nanoparticles effectively kill tumor cells in cell experiments. The detection results of CRT, ATP, and HMGB1 levels indicate that the siTOX-loaded fluorinated polymer nanoparticles can induce significant immunogenic cell death in 4T1 cells. The DC cell maturation results show that 4T1 cells treated with siTOX-loaded fluorinated polymer nanoparticles can be induced to mature into DC cells.

[0059] Example 4: The gene-loaded fluorinated polymer nanoparticles prepared in Example 1 were used as controls to study their induction of immune cells and inhibition of TOX in tumor-bearing mice, as well as their antitumor and anti-metastatic effects on 4T1 or B16F10 tumor-bearing mice.

[0060] The specific method is as follows:

[0061] Experiment (1): Female BALB / c mice weighing 18–22 g were randomly divided into 4 groups of 5 mice each. Each mouse was subcutaneously injected with 1 × 10⁻⁶ mol / L on the left side. 6 A primary solid tumor model was constructed using 4T1 cells. After 7 days, the solid tumor grew to approximately 150 mm. 3 At that time, mice in four groups were injected intravenously with saline and 4 mg / kg free doxorubicin, as well as siNC-loaded fluorinated polymer nanoparticles and siTOX-loaded fluorinated polymer nanoparticles containing 4 mg / kg doxorubicin and 2 mg / kg gene, respectively. The injections were administered every two days for a total of four times. Seven days after the last injection, tumor tissue and lymph nodes were collected from the mice to examine changes in immune cells.

[0062] Experiment (2): Using the same modeling and injection administration method as Experiment (1) in this embodiment, 5 × 10⁵ g of the drug was injected into the tail vein of each mouse 3 days after the last injection. 5 A tumor metastasis model was constructed using 4T1 cells, and tumor and lung tissue were collected 11 days later. Mice were weighed and tumor size and volume (mm³) were measured every two days during treatment. 3 = 0.5 × length × width 2 .

[0063] Experiment (3): The survival period of mice was studied for 60 days using the same modeling and injection administration method as in Experiment (1) of this embodiment.

[0064] Experiment (4): Female C57BL / 6 mice weighing 18–22g were divided into 4 groups of 5 mice each, and 1×10⁻⁶ mice were subcutaneously injected into their right back. 6 A melanoma model was constructed using B16F10 cells. Four days later, when the tumor had grown to approximately 50 mm... 3 C57BL / 6 mice were treated with the same injection regimen as BALB / c mice, with injections every 2 days for a total of 5 times. Tumor size and mouse weight were recorded during treatment. Twenty days after modeling, tumor tissue was collected and weighed.

[0065] Experiment (5): 8×10⁸ g of iodine solution was injected into the tail vein of C57BL / 6 mice. 5 A B16F10 cell line was used to construct a transfer model. The mice were treated with the same injection method as in experiment (4) of this embodiment every other day. The lung tissue of the mice was collected 15 days later.

[0066] like Figure 1 This is a schematic diagram of the self-assembly of fluorinated polymer nanoparticles and a schematic diagram of their anti-tumor and anti-metastasis mechanisms.

[0067] like Figure 4 As shown, the results of DC cell maturation detected by CD80 and CD86 antibodies indicate that siTOX-loaded fluorinated polymer nanoparticles can significantly induce DC cell maturation. The results of T cell level detection by CD3 and CD8 antibodies indicate that siTOX-loaded fluorinated polymer nanoparticles can enhance CD8 cell maturation. + T cell infiltration in tumor tissue. PD1 and TIM3 assays of exhausted T cells showed that siTOX-loaded fluorinated polymer nanoparticles significantly downregulated exhausted T cell levels, while siNC-loaded fluorinated polymer nanoparticles did not exhibit this downregulation. This indicates that fluorinated polyethylene glycol-fluorinated doxorubicin polymers, acting as gene carriers, can effectively deliver siTOX to downregulate exhausted T cell levels. TOX level assays further demonstrated that siTOX delivery via siTOX-loaded fluorinated polymer nanoparticles inhibited TOX protein expression.

[0068] like Figure 5 As shown, tumor volume and weight changes indicated that tumors in mice treated with siTOX-loaded fluorinated polymer nanoparticles grew most slowly. Body weight and survival results showed that mice in the siTOX-loaded fluorinated polymer nanoparticle treatment group did not experience significant weight loss compared to the control group, and their survival time was prolonged. Lung tissue imaging results demonstrated that siTOX-loaded fluorinated polymer nanoparticles significantly inhibited lung metastasis of mouse 4T1 cells.

[0069] like Figure 6 As shown, tumor volume and weight indicate that melanoma in mice treated with siTOX-loaded fluorinated polymer nanoparticles was most significantly suppressed within the same timeframe. Survival results showed that nanoparticle treatment prolonged mouse survival compared to free doxorubicin treatment. Lung tissue analysis revealed that siTOX-loaded fluorinated polymer nanoparticles significantly inhibited lung metastasis of mouse B16F10 cells.

[0070] The above-described embodiments are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. Those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a nanocarrier based on a fluorinated polymer, characterized in that, Includes the following steps: (1) Using 2,2,3,3,4,4,5,5,6,6,7,7-dodecano-1,8-octanediol, oxaloyl chloride and polyethylene glycol as raw materials, the mixture was polymerized, dialyzed and freeze-dried to obtain compound I; ； (2) Using 3,5-bis(trifluoromethyl)benzaldehyde and doxorubicin as raw materials, compound II was obtained through Schiff base formation reaction; ； (3) Using the compounds I and II as raw materials, a fluorine-fluorine interaction occurs in a dimethyl sulfoxide solvent to obtain a fluorinated polyethylene glycol-fluorinated doxorubicin polymer; (4) Add the fluorinated polyethylene glycol-fluorinated doxorubicin polymer obtained in step (3) to water, dialyze, freeze dry, and obtain a nanocarrier based on the fluorinated polymer.

2. The method as described in claim 1, characterized in that, In step (1), the polymerization reaction takes 0.5 h to 60 h, the molar ratio of 2,2,3,3,4,4,5,5,6,6,7,7-dodecano-1,8-octanediol, oxaloyl chloride, and polyethylene glycol is 1:(1-15):1, the reaction temperature range is 0 to 99℃, and the molecular weight of the polyethylene glycol is 100-10000.

3. The method as described in claim 1, characterized in that, In step (2), the reaction time is 0.5 h – 240 h, the molar ratio of 3,5-bis(trifluoromethyl)benzaldehyde to doxorubicin is 0.1-10:1, and the reaction temperature range is 0 – 99 °C.

4. The method as described in claim 1, characterized in that, In step (3), the time for fluorine-fluorine interaction is 0.5 h – 24 h, and the temperature range for fluorine-fluorine interaction is 0 – 99℃.

5. The method as described in claim 1, characterized in that, In step (3), the mass ratio of compound I to compound II is 0.01–100.

6. The method as described in claim 1, characterized in that, In step (4), the stirring is continued for 0.5 h to 24 h during the dropwise addition process, and the dropwise addition concentration range is 0.1 to 10 mg / mL.

7. A fluorinated polymer-based nanocarrier prepared by the method according to any one of claims 1 to 6.

8. A fluorinated polymer nanoparticle system for carrying gene-loaded drugs, characterized in that, The preparation method is as follows: after dissolving the nucleic acid drug, it is thoroughly mixed with the fluorinated polymer-based nanocarrier described in claim 7 in an aqueous solution. The mass ratio of the nucleic acid drug to the fluorinated polymer nanocarrier is 1:0.01-100. After standing, the fluorinated polymer nanoparticle system carrying the gene drug is obtained.

9. The fluorinated polymer nanoparticle system for gene-carrying drugs as described in claim 8, characterized in that, The settling time is 5 min – 24 h.

10. The application of the fluorinated polymer-based nanocarrier as described in claim 7 or the fluorinated polymer nanoparticle system for gene-carrying drugs as described in claim 9 in the preparation of drugs for treating human solid tumor cancer.

Images