Targeted drug delivery carrier based on mesoporous polydopamine nanoparticles and application

Abstract

The invention relates to a targeted drug delivery carrier based on mesoporous polydopamine nanoparticles and application thereof.The targeted drug delivery carrier is galactose modified mesoporous dopamine coordinated with manganese ions, lysine is adopted in the carrier synthesis step to provide an alkaline environment needed by dopamine polymerization, the polymerization process is simplified, and the drug delivery efficiency is improved. Meanwhile, lysine can be introduced into the mesoporous polydopamine; and the drug loading capacity of the carrier is improved. The carrier gathers multifunctionality of drug delivery, tumor imaging and treatment, provides a comprehensive new method for tumor treatment, and enhances individuation and precision of treatment.

Description

Technical Field

[0001] The invention belongs to the field of biomedical engineering materials, and in particular relates to a targeted drug delivery carrier based on mesoporous polydopamine nanoparticles and an application thereof. Background Art

[0002] Currently in clinical practice, chemotherapy remains the mainstream strategy for treating cancer. However, monotherapy has failed to significantly improve survival rates, and the efficacy is far from satisfactory. Many traditional chemotherapeutic drugs have problems with low water solubility, poor stability, and rapid blood clearance. In addition, the nonspecific delivery of chemotherapeutic drugs largely weakens the anti-cancer effect and may cause severe systemic toxicity. In addition, the occurrence of multidrug resistance (MDR) is a major obstacle to treatment. Traditional chemotherapeutic drugs such as doxorubicin and targeted drugs such as sorafenib are often difficult to effectively overcome drug resistance when used alone, and lack real-time imaging methods to monitor drug delivery and tumor response. Therefore, it is of great clinical significance to develop a drug delivery carrier that can enhance drug delivery efficiency, overcome drug resistance, and provide real-time imaging.

[0003] Nanocarrier technology has received extensive attention in recent years. Nanocarriers can optimize drug loading capacity and release characteristics by changing their physicochemical properties. Among them, mesoporous polydopamine nanoparticles have become a promising drug delivery system due to their excellent biocompatibility, adjustable pore size and surface properties. This nanocarrier can not only effectively load anti-tumor drugs, but also achieve precise targeted release in vivo. Through reasonable design, nanocarriers can release drugs in response to the characteristics of the tumor microenvironment (such as pH value, enzyme activity, etc.), thereby increasing the accumulation of drugs at the tumor site.

[0004] In addition, manganese ion is a good MRI imaging contrast agent and has been widely used in the field of biomedical imaging in recent years. In addition, studies have shown that lysine can not only promote cell proliferation, repair and growth, but is also considered to have a potential regulatory role in the tumor microenvironment. Summary of the invention

[0005] In view of the above-mentioned current technical deficiencies, the present invention provides a targeted drug delivery carrier based on mesoporous polydopamine nanoparticles and its application.

[0006] The technical solution of the present invention is as follows:

[0007] The present invention provides a targeted drug delivery carrier based on mesoporous polydopamine nanoparticles, wherein the carrier is prepared by the following method, comprising the steps of:

[0008] Preparation of mesoporous dopamine nanoparticles modified with S1-coordinated manganese ions and arginine.

[0009] S11 disperses dopamine hydrochloride and hydrated manganese sulfate in water to react to obtain a dopamine-manganese chelate solution;

[0010] S12: Pluronic F127, anhydrous ethanol and water are mixed, and then added to the dopamine-manganese chelate solution synthesized in step S11 and dispersed until completely dissolved, and then 1,3,5-trimethylbenzene solution is slowly added to the mixed solution under ultrasonic conditions, and continuously oscillated in a water bath until the solution becomes milky white, and then L-arginine solution is added, stirred to react in the dark, and finally washed and dried to obtain mesoporous dopamine nanoparticles modified with coordinated manganese ions and arginine, which are recorded as AMn-MPDA;

[0011] Preparation of S2 galactose-modified AMn-MPDA,

[0012] Dissolve galactose Gal and AMn-MPDA in water, mix and stir to react, and finally centrifuge to obtain galactose-modified AMn-MPDA.

[0013] In this synthesis step, lysine is used to provide the alkaline environment required for dopamine polymerization, which not only simplifies the polymerization process, but also introduces lysine into mesoporous polydopamine, which can significantly improve the encapsulation rate and drug loading rate of nanoparticles. The synthesized targeted drug delivery carrier uses mesoporous polydopamine as the carrier core, and the carrier surface is modified with galactose, which can enhance its targeting to tumor cells, especially liver cancer cells, while improving biocompatibility; the introduction of manganese ions adds MRI imaging function to this delivery platform to dynamically monitor the distribution of drugs in liver cancer models and the response of tumors. Bringing together the versatility of drug delivery, tumor imaging and treatment, it provides a comprehensive new method for tumor treatment and enhances the personalization and precision of treatment.

[0014] Preferably, in step S11, dopamine hydrochloride: water: hydrated manganese sulfate = 50-120 mg: 3-8 mL: 1-5 mg; the reaction time is 18-36 h. In a preferred embodiment of the present invention, dopamine hydrochloride: water: hydrated manganese sulfate = 90 mg: 3 mL: 3 mg; the reaction time is 24 h.

[0015] Preferably, in step S12, Pluronic F127: water: anhydrous ethanol: dopamine-manganese chelate solution: 1,3,5-trimethylbenzene solution: L-arginine = 30-40 mg: 2-8 mL: 2-8 mL: 0.3-1.2 mL: 0.3-0.5 mL: 8-12 mg; the reaction time under light-proof stirring is 4-8 hours. In a preferred embodiment of the present invention, Pluronic F127: water: anhydrous ethanol: dopamine-manganese chelate solution: 1,3,5-trimethylbenzene solution: L-arginine = 36 mg: 6 mL: 6 mL: 0.3 mL: 0.3 mL: 9 mg; the reaction time under light-proof stirring is 6 hours.

[0016] Preferably, in step S2, GaL:AMn-MPDA=10-30mg:30-50mg; the centrifugal speed is 8000-12000rpm, and the centrifugal time is 10-20min. In a preferred embodiment of the present invention, GaL:AMn-MPDA=25mg:50mg; the centrifugal speed is 10000rpm, and the centrifugal time is 15min.

[0017] Preferably, in step (3), galactose is prepared by the following method:

[0018] (1) Preparation of intermediate: β-d-galactose pentaacetate and Fmoc-glycinol were added to dichloromethane, cooled to 0°C, and then boron trifluoride ether was added dropwise in an ice bath. After the addition was completed, stirring was continued, and then the mixture was stirred and dispersed at room temperature. Finally, the organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue, which was then purified by silica gel column chromatography to obtain a yellow intermediate.

[0019] (2) Synthesis of galactose: A certain amount of the intermediate was dissolved in DMF, and an excess of ethylenediamine was added. The mixture was reacted at room temperature. The mixture was concentrated in vacuo and dissolved in ethanol. A sodium hydroxide solution was added and the mixture was reacted at room temperature. After the reaction, the mixture was concentrated in vacuo and dissolved in ultrapure water. The aqueous layer was extracted with ethyl acetate, and then the aqueous layer was freeze-dried to obtain galactose Gal.

[0020] Preferably, in the step (1), β-d-galactose pentaacetate: Fmoc-glycinol: dichloromethane; = 10-15 g: 0.5-1.2 g: 40-60 mL; the reaction time is 10-18 h. In a preferred embodiment of the present invention, β-d-galactose pentaacetate: Fmoc-glycinol: dichloromethane; = 12 g: 0.75 g: 50 mL; the reaction time is 12 h.

[0021] Preferably, in step (2), intermediate: ethylenediamine: ethanol: sodium hydroxide = 1-5g: 0.5-1.5g: 10-30mL: 0.01-0.04g. In a preferred embodiment of the present invention, intermediate: ethylenediamine: ethanol: sodium hydroxide = 2g: 0.5g: 10mL: 0.02g.

[0022] The present invention also provides a targeted drug delivery platform, which includes the above-mentioned targeted drug delivery carrier based on mesoporous polydopamine nanoparticles and an anticancer drug loaded on the carrier.

[0023] Preferably, the weight ratio of the carrier to the anticancer drug is 1 to 3: 1. In a preferred embodiment of the present invention, the weight ratio of the carrier to the anticancer drug is 2:1.

[0024] Preferably, the anticancer drug is doxorubicin and / or sorafenib.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1) The targeted drug delivery carrier of the present invention uses lysine in the synthesis step to provide the alkaline environment required for dopamine polymerization, which not only simplifies the polymerization process, but also introduces lysine into the mesoporous polydopamine, and can significantly improve the encapsulation rate and drug loading rate of the nanoparticles for drugs.

[0027] 2) The carrier of the present invention uses hollow mesoporous polydopamine with manganese ion coordination as the core skeleton, can efficiently load a variety of anticancer drugs, and endows the nanocarrier with targeting tumor cells, especially targeting of liver cancer cells by modifying galactose, thereby achieving targeted treatment of liver cancer. At the same time, the coordination of manganese ions enables the nanocarrier to introduce imaging function, realize real-time imaging of the tumor site, and bring together the multifunctionality of drug delivery, tumor imaging and treatment. At the same time, by loading anticancer drugs of different mechanisms in nanoparticles, combined with different release characteristics, synergy between drugs can be achieved, further improving the anti-tumor effect. In addition, the components designed by this material are all degradable in vivo, and the biosafety of the material itself is effectively controlled during drug delivery.

[0028] 3) The carrier preparation of the present invention is simple, maintains the advantages of the original material, and the required raw materials are easily available, and is expected to be widely used in the field of biomedical engineering materials.

[0029] 4) The present invention not only improves the biocompatibility and safety of the carrier by optimizing the material composition and preparation process, but also enhances the targeting and efficiency of drug delivery, providing a more potential solution for tumor treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 Comparison of drug encapsulation efficiency and drug loading rate of different carriers;

[0031] Figure 2 Cytotoxicity test of the carrier Gal-AMn-MPDA;

[0032] Figure 3 The drug-carrying platform Gal-DS@AMn-MPDA kills liver cancer cells;

[0033] Figure 4 The release curve of the drug delivery platform Gal-DS@AMn-MPDA in different pH environments. DETAILED DESCRIPTION

[0034] The present invention is further described below in conjunction with specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0035] Example 1

[0036] A targeted drug delivery carrier Gal-AMn-MPDA based on mesoporous polydopamine nanoparticles, the preparation method of which comprises the following steps:

[0037] S1. Preparation of mesoporous dopamine nanoparticles AMn-MPDA modified with coordinated manganese ions S11. Dissolve 90 mg of dopamine hydrochloride and 3 mg of hydrated manganese sulfate in 3 mL of ultrapure water and stir for 24 h to form a dopamine-manganese chelate solution.

[0038] S12 Dissolve 36 mg of Pluronic F127 in a mixture of 6 ml of anhydrous ethanol and 6 ml of ultrapure water. Add 0.3 mL of dopamine-manganese chelate solution and stir for 20 minutes until completely dissolved. Then, slowly add 0.3 mL of 1,3,5-trimethylbenzene solution to the mixed solution under ultrasonic conditions and continuously oscillate in a water bath for 4 minutes until the solution turns milky white. Then add 1 ml of L-arginine solution (9 mg / mL) and stir in the dark for 6 hours. Finally, wash once with ethanol and twice with water to obtain AMn-MPDA.

[0039] S2. Preparation of galactose-modified AMn-MPDA

[0040] Preparation of S21 Gal

[0041] First, β-d-galactose pentaacetate (12 g) and Fmoc-glycinol (0.75 g) were added to 50 mL of dichloromethane (DCM) and cooled to 0°C. Boron trifluoride etherate (1.1 g) was then slowly added dropwise in an ice bath, stirred for 1 h, and then moved to room temperature and stirred for 12 h. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue, which was then purified by silica gel column chromatography (PE / EA=2:1) ​​to obtain an intermediate compound as a yellow solid.

[0042] Subsequently, 2.0 g of the intermediate was weighed and dissolved in 10 mL of DMF, 0.5 g of ethylenediamine was added, and the mixture was reacted at room temperature for 2 h. The obtained mixture was concentrated in vacuo and dissolved in 10 mL of anhydrous ethanol, 1 mL of sodium hydroxide solution (0.02 g / mL) was added dropwise, and the mixture was reacted at room temperature for 2 h. After the mixture was concentrated in vacuo, it was dissolved in ultrapure water, the aqueous layer was extracted with ethyl acetate, and the aqueous layer was freeze-dried to obtain Gal.

[0043] Preparation of S22 Gal-AMn-MPDA

[0044] Weigh 25 mg of Gal and 50 mg of AMn-MPDA and dissolve them in water, mix and stir for 6 h, centrifuge (10000 rpm, 15 min, 3 times) to obtain the target product, recorded as Gal-AMn-MPDA, resuspend it in water and set aside.

[0045] Comparative Example 1

[0046] A targeted drug delivery carrier Gal-Mn-MPDA based on mesoporous polydopamine nanoparticles, the preparation method of which comprises the following steps:

[0047] S1. Preparation of mesoporous polydopamine nanoparticles Mn-MPDA

[0048] S11 90 mg of dopamine hydrochloride and 3 mg of hydrated manganese sulfate were dissolved in 3 mL of ultrapure water and stirred for 24 h to form a dopamine-manganese chelate solution.

[0049] S12 Dissolve 36 mg of Pluronic F127 in a mixture of 6 ml of anhydrous ethanol and 6 ml of ultrapure water. Add 0.3 mL of dopamine-manganese chelate solution and stir for 20 minutes until completely dissolved. Then, slowly add 0.3 mL of 1,3,5-trimethylbenzene solution to the mixed solution under ultrasonic conditions and continuously oscillate in a water bath for 4 minutes until the solution turns milky white. Then add 1 ml of NaOH solution (0.5 mol / L) and stir in the dark for 6 hours. Finally, wash once with ethanol and twice with water to obtain Mn-MPDA.

[0050] S2. Preparation of Gal-Mn-MPDA

[0051] The preparation of S21 Gal is the same as in Example 1.

[0052] S22 Weigh 25 mg Gal and 50 mg Mn-MPDA and dissolve them in water, mix and stir for 6 h, centrifuge (10000 rpm, 15 min, 3 times) to obtain the target product, recorded as Gal-Mn-MPDA, resuspend it in water and set aside.

[0053] Application Examples

[0054] The carriers Gal-AMn-MPDA and Gal-Mn-MPDA prepared in Example 1 and Comparative Example 1 were loaded with doxorubicin (DOX) and sorafenib (SF) respectively to prepare drug loading platforms Gal-DS@AMn-MPDA and Gal-@Mn-MPDA. Specifically,

[0055] Weigh 15 mg of doxorubicin (DOX) and 15 mg of sorafenib (SF), dissolve them in 5 mL of ultrapure water respectively, weigh 30 mg of the carrier Gal-AMn-MPDA of Example 1 or the carrier Gal-Mn-MPDA of Comparative Example 1 and dissolve them in 10 mL of ultrapure water as carrier stock solution for standby use. Add the two drugs separately or mixed in stirring to the carrier stock solution, stir at room temperature for 24 hours, and collect the products Gal-DS@AMn-MPDA, Gal-D@AMn-MPDA, Gal-S@AMn-MPDA or Gal-DS@Mn-MPDA, Gal-D@Mn-MPDA, Gal-S@Mn-MPDA by centrifugation.

[0056] Performance Testing

[0057] 1. Drug loading

[0058] The loading amount of DOX and SF was detected by UV spectrophotometer at 480 nm and 240 nm, respectively. The encapsulation efficiency (1) and drug loading efficiency (2) were calculated according to the following formula, where w1 is the actual loading amount of the drug, w2 is the total input amount of the drug, and w3 is the total amount of the carrier and the drug.

[0059] EE (%) = w1 / w2×100% (1)

[0060] DLC (%) = w1 / w3×100% (2)

[0061] like Figure 1 As shown, the encapsulation efficiency and drug loading efficiency of the carrier Gal-AMn-MPDA in Example 1 were calculated to be 67.3% and 17.2% for DOX, and 73.5% and 21.3% for SF, respectively.

[0062] The optimal encapsulation efficiency and drug loading rate of the carrier Gal-Mn-MPDA in Comparative Example 1 for DOX were 55.1% and 10.4%, respectively, and the optimal encapsulation efficiency and drug loading rate for SF were 61.5% and 11.4%, respectively.

[0063] This shows that compared with the commonly used synthesis scheme, the use of lysine to provide an alkaline environment in the embodiments of the present invention can significantly improve the encapsulation efficiency and drug loading rate of the nanoparticles for drugs.

[0064] 2. Cytotoxicity

[0065] The method of detecting cell activity using CCK-8 was used to evaluate the cytotoxicity of Gal-AMn-MPDA to L929 and Huh-7 cells and Gal-DS@AMn-MPDA to Huh-7 cells. The specific steps are as follows: First, L929 or Huh-7 cells were seeded in a 96-well plate at a density of 5000 cells / well, and then placed in a carbon dioxide incubator to culture overnight. Subsequently, the original culture medium was aspirated and replaced with fresh complete culture medium containing different concentrations of Gal-AMn-MPDA or Gal-DS@AMn-MPDA. The selected concentration range of Gal-AMn-MPDA was 25-1000μg / mL, and the selected concentration range of Gal-DS@AMn-MPDA was 25-400μg / mL, with 5 parallels for each concentration. Then cultured in an incubator for 24h, washed the cells once with PBS after culture, and added 100μL of fresh culture medium (containing 10% CCK-8) to each well. The cells were placed in an incubator and incubated for a period of time. Finally, an ELISA reader was used to detect and record the absorbance at a wavelength of 450 nm. The cell survival rate was calculated using the following formula: cell survival rate (%) = (absorbance of the experimental group - absorbance of the blank group) / (absorbance of the negative control group - absorbance of the blank group) × 100%.

[0066] like Figure 2 As shown in the figure, when the concentration of Gal-AMn-MPDA is as high as 1000μg / mL, the cell survival rates of L929 and Huh-7 cells are 97.2% and 85.1%, respectively. It can be seen that even high concentrations of nanoparticles do not affect the proliferation of normal cells. The Gal-AMn-MPDA dose greater than 400μg / mL impairs the proliferation of Huh-7 cells, but the cell survival rate is still above 85%, which is higher than the 70% cytotoxicity threshold specified in ISO 10993-5. Gal-AMn-MPDA has an effect on the proliferation of Huh-7 cells, which may be because the microenvironment of tumor cells causes the nanoparticles to lyse, and the exposed manganese ions and lysine destroy the balance of the tumor microenvironment. The specific mechanism needs further study.

[0067] like Figure 3As shown in the figure, when the concentration of Gal-DS@AMn-MPDA was 400μg / mL, the survival rate of Huh-7 cells was only 20.3%, while the survival rates of Gal-D@AMn-MPDA and Gal-S@AMn-MPDA at the same concentration were 45.3% and 38.7%, respectively. This shows that the combination therapy achieved the expected effect and can enhance the killing of cancer cells by drugs. Figure 3 It can be seen from the curves in that the cell survival rate intervals of Gal-DS@AMn-MPDA, Gal-D@AMn-MPDA and Gal-S@AMn-MPDA gradually increase, which indicates that Gal-DS@AMn-MPDA can better exert the drug effect at higher concentrations, which can reduce the risk of drug resistance.

[0068] 3. Drug release curve of Gal-DS@AMn-MPDA

[0069] First, 2 ml of Gal-DS@AMn-MPDA solution (1 mg / mL) was added to a dialysis bag and immersed in 20 ml of phosphate buffered saline (PBS) containing 0.5% Tween80 (pH = 5.5, 7.4). Then, it was transferred to a constant temperature shaker (37°C, 100 rpm) for incubation. After that, 2 ml of PBS solution was taken at different time points and 2 ml of new PBS solution was added. The absorbance of the solution taken out at 240 nm was measured, and the drug release rate was calculated according to formula (3).

[0070] Drug release (%) = (C n ×V0+∑ cn-1 ×V1) / m0×100%(3)

[0071] Among them C n is the concentration of the nth sample, V0 is the total volume of the buffer, V1 is the volume of each sample, and m0 represents the total amount of drug in the sample.

[0072] like Figure 4 As shown in the figure, Gal-DS@AMn-MPDA is released faster in an acidic environment of pH 5.5 than in a neutral environment, which indicates that Gal-DS@AMn-MPDA can be well released in the tumor. In addition, at 12h, the drug release rate in the acidic environment reached more than 60%, which indicates that the drug has the function of quickly killing tumor cells after reaching the tumor site.

[0073] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0074] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A targeted drug delivery carrier based on mesoporous polydopamine nanoparticles, characterized in that: The carrier is prepared by the following method, comprising the steps of: Preparation of mesoporous dopamine nanoparticles modified with S1-coordinated manganese ions and arginine. S11 disperses dopamine hydrochloride and hydrated manganese sulfate in water to react to obtain a dopamine-manganese chelate solution; S12: Pluronic F127, anhydrous ethanol and water are mixed, and then added to the dopamine-manganese chelate solution synthesized in step S11 and dispersed until completely dissolved, and then 1,3,5-trimethylbenzene solution is slowly added to the mixed solution under ultrasonic conditions, and continuously oscillated in a water bath until the solution becomes milky white, and then L-arginine solution is added, stirred to react in the dark, and finally washed and dried to obtain mesoporous dopamine nanoparticles modified with coordinated manganese ions and arginine, which are recorded as AMn-MPDA; Preparation of S2 galactose-modified AMn-MPDA, Dissolve galactose Gal and AMn-MPDA in water, mix and stir to react, and finally centrifuge to obtain galactose-modified AMn-MPDA.

2. The drug delivery carrier according to claim 1, characterized in that In the step S11, dopamine hydrochloride: water: hydrated manganese sulfate = 50-120 mg: 3-8 mL: 1-5 mg; the reaction time is 18-36 h.

3. The drug delivery carrier according to claim 1, characterized in that In the step S12, Pluronic F127: water: anhydrous ethanol: dopamine-manganese chelate solution: 1,3,5-trimethylbenzene solution: L-arginine = 30-40 mg: 2-8 mL: 2-8 mL: 0.3-1.2 mL: 0.3-0.5 mL: 8-12 mg; the reaction time is 4-8 hours with stirring in the dark.

4. The drug delivery carrier according to claim 1, characterized in that In the step S2, GaL:AMn-MPDA=10-30mg:30-50mg; the centrifugal speed is 8000-12000rpm, and the centrifugal time is 10-20min.

5. The drug delivery carrier according to claim 1, characterized in that The galactose is prepared by the following method: (1) Preparation of intermediate: β-d-galactose pentaacetate and Fmoc-glycinol were added to dichloromethane, cooled to 0°C, and then boron trifluoride ether was added dropwise in an ice bath. After the addition was completed, stirring was continued, and then the mixture was stirred and dispersed at room temperature. Finally, the organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oily residue, which was then purified by silica gel column chromatography to obtain a yellow intermediate. (2) Synthesis of galactose: A certain amount of the intermediate was dissolved in DMF, and an excess of ethylenediamine was added. The mixture was reacted at room temperature. The mixture was concentrated in vacuo and dissolved in ethanol. A sodium hydroxide solution was added and the mixture was reacted at room temperature. After the reaction, the mixture was concentrated in vacuo and dissolved in ultrapure water. The aqueous layer was extracted with ethyl acetate, and then the aqueous layer was freeze-dried to obtain galactose Gal.

6. The drug delivery carrier according to claim 5, characterized in that In the step (1), β-d-galactose pentaacetate: Fmoc-glycinol: dichloromethane = 10-15 g: 0.5-1.2 g: 40-60 mL; the reaction time is 10-18 h.

7. The drug delivery carrier according to claim 5, characterized in that In the step (2), intermediate: ethylenediamine: ethanol: sodium hydroxide = 1-5 g: 0.5-1.5 g: 10-30 mL: 0.01-0.04 g.

8. A targeted drug delivery platform, characterized in that: The delivery platform comprises the carrier according to any one of claims 1 to 7, and an anticancer drug loaded on the carrier.

9. The targeted drug delivery platform according to claim 8, characterized in that: The weight ratio of the carrier to the anticancer drug is 1 to 3:

1.

10. The targeted drug delivery platform according to claim 8, characterized in that: The anticancer drugs are doxorubicin and / or sorafenib.

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