Nanoparticles based on amphiphilic block copolymer as well as construction method and application of nanoparticles
The synthesis of amphiphilic block copolymers via organotelluric compound-mediated free radical polymerization overcomes the shortcomings of existing block copolymer synthesis technologies, achieving core-shell nanoparticles with high conversion rates and controllable molecular weight, thereby improving the efficiency and stability of drug delivery.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NORTHWESTERN POLYTECHNICAL UNIV
- Filing Date
- 2026-02-11
- Publication Date
- 2026-04-24
Smart Images
Figure CN121914348A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of polymer materials and biomedical materials technology. Background Technology
[0002] Amphiphilic block copolymers, containing both hydrophilic and hydrophobic segments, can spontaneously form nanoscale self-assembled structures such as micelles, vesicles, or laminae in selective solvents through hydrophobic interactions and intermolecular forces. These nano-assemblies typically exhibit a "hydrophobic core-hydrophilic shell" structure; the hydrophobic core can serve as a drug carrier, while the hydrophilic shell enhances dispersibility and stability, thus attracting widespread attention in drug delivery and controlled-release systems. Furthermore, amphiphilic block copolymers, combining the low surface energy of fluorocarbon chains with the self-assembly properties of copolymer nanoparticles, show potential applications in drug delivery, medical imaging, and functional materials.
[0003] However, existing controlled radical polymerization methods, such as reversible addition-fragmentation chain transfer polymerization (RAFT), atom transfer radical polymerization (ATRP), and nitroxide radical-mediated polymerization (NMP), have significant shortcomings in synthesizing block copolymers of fluorinated acrylates and hydrophilic monomers. On the one hand, the polymerization reactivity of fluorinated acrylate monomers is low, easily leading to low conversion rates and limited chain growth. On the other hand, the poor compatibility between these monomers and polar hydrophilic monomers often results in insufficient block bonding efficiency and a wide molecular weight distribution, making it difficult to achieve precise control of the block structure. These problems directly affect the uniformity and size controllability of nanoparticle self-assembly, reduce drug loading efficiency and release stability, and limit the promotion of related materials in drug delivery and functional applications. Summary of the Invention
[0004] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a method for synthesizing amphiphilic block copolymers composed of hydrophobic fluorinated segments and hydrophilic amine segments through free radical polymerization mediated by organotelluric compounds. No metal catalysts or sulfur-containing chain transfer agents are required throughout the polymerization process. The organotelluric compound maintains reversible chain transfer activity in both the first and second block polymerization reactions, allowing the first block polymer to directly initiate the second block polymerization reaction without separation. Furthermore, the invention discloses amphiphilic block copolymer-based nanoparticles, which form uniform core-shell nanoparticles through solvent-induced self-assembly, along with their construction method and applications.
[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a method for constructing nanoparticles based on amphiphilic block copolymers, specifically including the following steps: Step 1: Using an organic tellurium compound as a chain transfer agent, free radical polymerization is carried out to prepare an amphiphilic block copolymer. The specific process is as follows: Under inert gas protection, organic tellurium compounds and azo initiators are dissolved in dimethyl sulfoxide, and then fluorinated acrylate monomers are added to carry out the first block polymerization reaction. The molar ratio of the organic tellurium compound to the azo initiator is 1:0.1 to 1:1. After the first block polymerization reaction reaches a conversion rate of fluorinated acrylate monomers ≥95%, a dimethyl sulfoxide solution of acrylamide monomers is added, along with an azo initiator, to carry out the second block polymerization reaction. The second block polymerization reaction was terminated after the conversion rate of acrylamide monomers was ≥95%, and the reaction was purified to obtain the amphiphilic block copolymer. The molecular weight of the amphiphilic block copolymer is 10~500 kDa, and the molecular weight distribution is less than 1.5. Step 2: Dissolve the amphiphilic block copolymer in dimethyl sulfoxide solvent to form an amphiphilic block copolymer solution with a concentration of 1-20 mg / mL. Then, under stirring conditions of 400-1000 rpm, add the amphiphilic block copolymer solution dropwise to deionized water at a dropping rate of 0.1-2.0 mL / min. After the addition is complete, continue stirring for 1-5 h to obtain nanoparticles formed by the self-assembly of the amphiphilic block copolymer in the aqueous phase. The amphiphilic block copolymer includes hydrophobic segments and hydrophilic segments. The hydrophobic segments are composed of fluorinated acrylate monomers, and the hydrophilic segments are composed of acrylamide monomers. The molar ratio of the hydrophobic segments to the hydrophilic segments is 3:1 to 1:3. The volume ratio of deionized water to the amphiphilic block copolymer solution is 5:1 to 20:1. Meanwhile, the dropping rate is used to avoid the formation of irregularly shaped aggregates when the dropping rate is too fast or the water phase ratio is insufficient. The stirring speed is used to ensure the formation of nanoparticles.
[0006] Furthermore, the hydrophobic segment is polyhexafluorobutyl acrylate, and the average degree of polymerization of polyhexafluorobutyl acrylate is 50~500; The hydrophilic segment is polyacrylamide, and the average degree of polymerization of polyacrylamide is 15~1500.
[0007] Furthermore, the reaction temperatures of the first block polymerization reaction and the second block polymerization reaction are both 60~80℃. At the same time, after the conversion rate of the fluorinated acrylate monomer in the first block polymerization reaction is ≥95%, it is first cooled to room temperature before adding the dimethyl sulfoxide solution of the acrylamide monomer.
[0008] Furthermore, in step one, the general structural formula of the organic tellurium compound is R. 1 –Te–R 2 ,in: R1 For C6-C 12 An ester derivative of one or any one of aryl, C1-C6 alkoxy, carboxyl, cyano, or C1-C6 straight-chain or branched alkyl groups; R 2 C1-C6 alkyl, C6-C 12 One of aryl and substituted aryl; The azo initiator is an organic azo initiator.
[0009] Furthermore, the R 1 It is any one of aryl, ester, carboxyl, cyano, and C1-C6 straight-chain or branched alkyl groups; Wherein, the aryl group is phenyl or p-methoxyphenyl; The R 2 It is one of methyl, ethyl, phenyl, and p-methoxyphenyl; The azo initiator is one of azobisisobutyronitrile, azobisisovalerate, and azobiscyclohexylformitrile.
[0010] Furthermore, the inert gas mentioned in step one is nitrogen or argon.
[0011] Furthermore, in step two, the amphiphilic block copolymer solution is added dropwise to deionized water at a stirring temperature of 20~40℃.
[0012] The present invention also provides nanoparticles prepared by the above-described method for constructing nanoparticles based on amphiphilic block copolymers. The nanoparticles have a core-shell structure, with a hydrophilic shell and a hydrophobic core. The nanoparticles are spherical in shape and have a particle size of 20-200 nm.
[0013] The present invention also provides an application of the nanoparticles, which utilize the responsiveness of the nanoparticles to environmental pH values to exhibit particle size changes under different pH conditions, thereby achieving controlled drug release.
[0014] The present invention also provides an application of nanoparticles in drug delivery, wherein when the nanoparticles are encapsulated with a hydrophobic drug, the drug loading efficiency of the nanoparticles is greater than 30%; Among them, the hydrophobic drug is any one of paclitaxel, irinotecan, and coumarin.
[0015] The beneficial effects of this invention are: This invention provides a method for constructing nanoparticles based on amphiphilic block copolymers, which adopts the organotelluric acid-mediated free radical polymerization (TERP) method. That is, it utilizes the efficient chain transfer ability and excellent monomer compatibility of organotelluric acid compounds to achieve high-conversion block polymerization of hydrophilic and hydrophobic monomers such as fluorinated acrylates and acrylamides under mild conditions. The resulting copolymer has a controllable molecular weight and narrow distribution, and can form uniform core-shell nanoparticles through solvent-induced self-assembly. Meanwhile, under the premise of ensuring monodispersity during the preparation process, the two monomers can be almost quantitatively converted, with high atom utilization rate, achieving the goal of green chemistry; the monomers can be quantitatively converted, and nanoparticles of different particle sizes can be designed by changing the feed ratio; the amide groups on the outside of the nanoparticles are neutral in water, have good in vivo tolerance, and can also have acid and alkali responsiveness; the nanoparticles contain fluorine atoms that are not easily found in living organisms, and have good imaging effect.
[0016] The resulting nanomaterials exhibit excellent dispersion stability and monodispersity, overcoming the limitations of existing technologies in terms of monomer applicability and conversion rate, and significantly expanding the application scope of amphiphilic block copolymers in the field of drug delivery. Attached Figure Description
[0017] Figure 1 The representative amphiphilic block copolymer of this invention is PHFBA- b -Schematic diagram of PAM structure; Figure 2 Transmission electron microscope image of the core-shell nanoparticles constructed in this invention; Figure 3 This invention provides transmission electron microscopy and X-ray energy dispersive spectroscopy (EDS) images of nanoparticles formed by solvent displacement of copolymers in Specific Example 1 of the present invention. In the image, (a) is a transmission electron microscope image, and (b) is the X-ray energy dispersive spectroscopy (EDS) diagram corresponding to the transmission electron microscope image. Detailed Implementation
[0018] The principles and features of the present invention are described below with reference to the accompanying drawings. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention.
[0019] To achieve the above objectives, the present invention provides the following specific embodiments: Example 1: A method for constructing nanoparticles based on amphiphilic block copolymers, wherein the nanoparticles are formed by the self-assembly of amphiphilic block copolymers in an aqueous phase; The amphiphilic block copolymer includes hydrophobic segments and hydrophilic segments. The hydrophobic segments are composed of fluorinated acrylate monomers, and the hydrophilic segments are composed of acrylamide monomers. The molar ratio of the hydrophobic segments to the hydrophilic segments is 3:1 to 1:3. The specific construction method includes the following steps: Step 1: Using an organic tellurium compound as a chain transfer agent, free radical polymerization is carried out to prepare an amphiphilic block copolymer. The specific process is as follows: Under nitrogen gas protection, organic tellurium compounds and azo initiators are dissolved in dimethyl sulfoxide, and then fluorinated acrylate monomers are added to carry out the first block polymerization reaction. The molar ratio of the organic tellurium compound to the azo initiator is 1:0.1 to 1:1. The general structural formula of organotelluric compounds is R 1 –Te–R 2 ,in: R 1 For C6-C 12 An ester derivative of one or any one of aryl, C1-C6 alkoxy, carboxyl, cyano, or C1-C6 straight-chain or branched alkyl groups; R 2 C1-C6 alkyl, C6-C 12 One of aryl and substituted aryl; The azo initiator is an organic azo initiator; After the first block polymerization reaction reaches a conversion rate of fluorinated acrylate monomers ≥95%, a dimethyl sulfoxide solution of acrylamide monomers is added, along with an azo initiator, to carry out the second block polymerization reaction. The second block polymerization reaction was terminated after the conversion rate of acrylamide monomers was ≥95%, and the reaction was purified to obtain the amphiphilic block copolymer. The molecular weight of the amphiphilic block copolymer is 10~500 kDa, and the molecular weight distribution is less than 1.5.
[0020] Step 2: Dissolve the amphiphilic block copolymer in dimethyl sulfoxide solvent to form an amphiphilic block copolymer solution with a concentration of 1-20 mg / mL. Then, under stirring conditions of 400-1000 rpm, add the amphiphilic block copolymer solution dropwise to deionized water at a dropping rate of 0.1-2.0 mL / min. After the addition is complete, continue stirring for 1-5 h to obtain nanoparticles formed by the self-assembly of the amphiphilic block copolymer in the aqueous phase. The volume ratio of deionized water to the amphiphilic block copolymer solution is 5:1 to 20:1. Meanwhile, the dropping rate is used to avoid the formation of irregularly shaped aggregates when the dropping rate is too fast or the water phase ratio is insufficient. The stirring speed is used to ensure the formation of nanoparticles.
[0021] Example 2: Same as Example 1, except that the hydrophobic segment is polyhexafluorobutyl acrylate, and the average degree of polymerization of polyhexafluorobutyl acrylate is 50~500. The hydrophilic segment is polyacrylamide, and the average degree of polymerization of polyacrylamide is 15~1500.
[0022] Example 3: Same as Example 1, except that in step one, the organic tellurium compound and azo initiator are dissolved in dimethyl sulfoxide under argon gas protection, and then fluorinated acrylate monomers are added to carry out the first block polymerization reaction. The reaction temperatures for both the first and second block polymerization reactions are 60-80℃. Meanwhile, after the conversion rate of the fluorinated acrylate monomers in the first block polymerization reaction reaches ≥95%, it is first cooled to room temperature, and then a dimethyl sulfoxide solution of acrylamide monomers is added. Meanwhile, in step two, the amphiphilic block copolymer solution is added dropwise to deionized water at a stirring temperature of 20~40℃.
[0023] Example 4: Same as Example 1, except that the general structural formula of the organic tellurium compound in step one is R. 1 –Te–R 2 ; Among them, R 1 It is any one of aryl, ester, carboxyl, cyano, and C1-C6 straight-chain or branched alkyl groups; Wherein, the aryl group is phenyl or p-methoxyphenyl; R 2 It is one of methyl, ethyl, phenyl, and p-methoxyphenyl; The azo initiator is one of azobisisobutyronitrile, azobisisovalerate, or azobiscyclohexylformitrile.
[0024] Example 5: The present invention also provides nanoparticles prepared by the nanoparticle construction method based on amphiphilic block copolymers as described in Examples 1-4. The nanoparticles have a core-shell structure, with a hydrophilic shell and a hydrophobic core. The nanoparticles are spherical in shape and have a particle size of 20-200 nm.
[0025] Example 6: As Figure 2 As shown, the present invention also provides an application of the nanoparticles described in Example 5, utilizing the responsiveness of the nanoparticles to environmental pH values, exhibiting particle size changes under different pH conditions, thereby achieving controlled drug release. For example... Figure 2 As shown, when the pH changes from near neutral to acidic, the diameter of the nanoparticles increases significantly while still maintaining good monodispersity.
[0026] Example 7: The present invention also provides the application of the nanoparticles described in Example 5 in drug delivery, wherein when the nanoparticles are encapsulated with a hydrophobic drug, the drug loading efficiency of the nanoparticles is greater than 30%; Among them, the hydrophobic drug is any one of paclitaxel, irinotecan, and coumarin.
[0027] like Figure 1 , Figure 3 As shown, to further illustrate the technical solution and effects of the present invention, the following specific examples are provided: Specific Example 1: A method for constructing nanoparticles based on amphiphilic block copolymers. Under nitrogen protection, 20 μL (0.25 mmol) of methyl 2-telluride-isobutyrate and 8.2 mg (0.05 mmol) of azobisisobutyronitrile (AIBN) were added to a three-necked flask with a magnetic stirrer. 2 mL of deoxygenated dimethyl sulfoxide (DMSO) was added, and after stirring until homogeneous, 2.3 mL (14 mmol) of hexafluorobutyl acrylate (HFBA) was added. The mixture was heated to 65°C and reacted for 4 hours. The monomer conversion rate was confirmed to be 99% by 1H NMR spectroscopy, indicating the completion of the first block polymerization reaction and the acquisition of the first hydrophobic block. Subsequently, 8 mL of 1.78 g (25 mmol) acrylamide (AM) in DMSO solution was added to the reactor, along with 8.2 mg (0.05 mmol) AIBN. After reacting for another 12 hours, the monomer conversion rate was confirmed to be 98% by nuclear magnetic resonance hydrogen spectroscopy, thus completing the second block polymerization reaction. After terminating the second block polymerization reaction and purifying, the amphiphilic block copolymer PHFBA- was obtained. b -PAM, with a molecular weight of 30.8 kDa and a molecular weight distribution of 1.27 as determined by gel permeation chromatography (GPC). Its molecular structure is as follows: Figure 1 As shown, this is a representative amphiphilic block copolymer of the present invention, PHFBA- b -Structure diagram of PAM.
[0028] The copolymer was converted into nanoparticles via solvent displacement. Dynamic light scattering (DLS) analysis revealed a particle size of 80 nm and a polydispersity index (PDI) of 0.12, exhibiting good monodispersity. Its transmission electron microscope image is shown below. Figure 3 As shown in the figure, the nanoparticles are micellar nanoparticles with a bilayer structure. The outer layer is composed of hydrophilic PAM segments and the inner layer is composed of hydrophobic PHFBA segments. In the figure, green represents nitrogen and red represents fluorine, which proves that the outer layer of the particle is PAM and the inner layer is PHFBA.
[0029] Finally, nanoparticles for drug delivery were obtained, and the drug loading performance of a model drug encapsulating the hydrophobic drug coumarin 6 was tested, using PHFBA synthesized in Specific Example 1. b -PAM copolymer is dissolved in DMSO and co-dissolved with coumarin 6 at a copolymer:drug mass ratio of 10:1.
[0030] The mixture was slowly added dropwise to deionized water using a solvent displacement method, allowing the drug and copolymer to simultaneously self-assemble into drug-loaded nanoparticles. The resulting micellar nanoparticles were then subjected to ultrafiltration or dialysis to remove unloaded free drug. The collected micellar nanoparticles were then analyzed using a UV-Vis spectrophotometer to measure the absorption intensity of coumarin 6 at 460 nm, indirectly calculating the encapsulation efficiency and drug loading.
[0031] In specific example 2, the fluorinated acrylate monomer is replaced with octafluoropentyl acrylate. Under the same operating conditions as in specific implementation 1, an equimolar amount of octafluoropentyl acrylate (OFPA) is used to replace HFBA to synthesize poly(OFPA- b The -AM) block copolymers, with monomer conversion rates of 99% and 97%, yielded a molecular weight of 28.7 kDa and a molecular weight distribution of 1.32, as determined by GPC. The self-assembled nanoparticles had a particle size of 95 nm and a PDI of 0.15, indicating good monodispersity, slightly larger particle size, enhanced hydrophobicity, and an approximately 12% increase in drug loading capacity.
[0032] Specific example 3: Replacing the acrylamide monomer with... N - Isopropylacrylamide (NIPAM), under the same polymerization conditions as in Specific Example 1, using N - Isopropylacrylamide (NIPAM) is used instead of AM in the second stage of polymerization, resulting in a copolymer called PHFBA- b -PNIPAM. The monomer conversion rates are 98% and 96%, respectively. The molecular weight is 32.2 kDa and the molecular weight distribution is 1.27. This copolymer self-assembles in the aqueous phase to form nanoparticles with a particle size of 78 nm. It exhibits a hydrophilic state below 25 °C and undergoes hydrophobic collapse above 35 °C, with the particle size decreasing to 55 nm, showing good temperature response.
[0033] Specific Example 4 verifies the polymerization of PHFBA alone. Following the method in Specific Example 1, only HFBA monomers are polymerized without adding acrylamide (AM), resulting in a PHFBA homopolymer. When introduced into an aqueous phase, it exhibits coarse aggregation, lacks a stable nanoparticle structure, and cannot form effective drug-loaded nanoparticles.
[0034] In Specific Example 5, without using an organotellurium compound (non-TERP method) for verification, PHFBA was synthesized using the traditional free radical polymerization method, following the proportions of Specific Example 1, omitting the organotellurium compound.b -AM copolymer. The resulting copolymer has a molecular weight distribution greater than 2.2 and a non-uniform particle size distribution. DLS shows multiple particle size peaks, and nanoparticle precipitation is obvious within 1 week.
[0035] In summary, the method provided by this invention achieves the design of drug delivery performance by regulating the copolymer structure, and is applicable to the development and application of targeted therapy, controlled-release formulations and environmentally responsive drug delivery systems; Among them, the fluorinated hydrophobic segments provide an excellent drug-encapsulating microenvironment and possess... 19 The copolymer exhibits potential for fMRI imaging; while the exposed amine groups (–NH2) in the hydrophilic segments endow the copolymer with good water solubility and pH responsiveness, which can be used to regulate the stability and release behavior of drug-loaded nanoparticles.
[0036] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for constructing nanoparticles based on amphiphilic block copolymers, characterized in that, Specifically, the following steps are included: Step 1: Using an organic tellurium compound as a chain transfer agent, free radical polymerization is carried out to prepare an amphiphilic block copolymer. The specific process is as follows: Under inert gas protection, organic tellurium compounds and azo initiators are dissolved in dimethyl sulfoxide, and then fluorinated acrylate monomers are added to carry out the first block polymerization reaction. The molar ratio of the organic tellurium compound to the azo initiator is 1:0.1 to 1:
1. After the first block polymerization reaction reaches a conversion rate of fluorinated acrylate monomers ≥95%, a dimethyl sulfoxide solution of acrylamide monomers is added, along with an azo initiator, to carry out the second block polymerization reaction. The second block polymerization reaction was terminated after the conversion rate of acrylamide monomers reached ≥95%, and the reaction was purified to obtain the amphiphilic block copolymer. The molecular weight of the amphiphilic block copolymer is 10~500 kDa, and the molecular weight distribution is less than 1.
5. Step 2: Dissolve the amphiphilic block copolymer in dimethyl sulfoxide solvent to form an amphiphilic block copolymer solution with a concentration of 1-20 mg / mL. Then, under stirring conditions of 400-1000 rpm, add the amphiphilic block copolymer solution dropwise to deionized water at a dropping rate of 0.1-2.0 mL / min. After the addition is complete, continue stirring for 1-5 h to obtain nanoparticles formed by the self-assembly of the amphiphilic block copolymer in the aqueous phase. The amphiphilic block copolymer includes hydrophobic segments and hydrophilic segments. The hydrophobic segments are composed of fluorinated acrylate monomers, and the hydrophilic segments are composed of acrylamide monomers. The molar ratio of the hydrophobic segments to the hydrophilic segments is 3:1 to 1:
3. The volume ratio of deionized water to the amphiphilic block copolymer solution is 5:1 to 20:
1. Meanwhile, the dropping rate is used to avoid the formation of irregularly shaped aggregates when the dropping rate is too fast or the water phase ratio is insufficient. The stirring speed is used to ensure the formation of nanoparticles.
2. The method for constructing nanoparticles based on amphiphilic block copolymers as described in claim 1, characterized in that, The hydrophobic segment is polyhexafluorobutyl acrylate, and the average degree of polymerization of polyhexafluorobutyl acrylate is 50~500; The hydrophilic segment is polyacrylamide, and the average degree of polymerization of polyacrylamide is 15~1500.
3. The method for constructing nanoparticles based on amphiphilic block copolymers as described in claim 1, characterized in that, The reaction temperature for both the first and second block polymerization reactions is 60~80℃. Meanwhile, after the conversion rate of fluorinated acrylate monomers in the first block polymerization reaction reaches ≥95%, the mixture is first cooled to room temperature before adding a dimethyl sulfoxide solution of acrylamide monomers.
4. The method for constructing nanoparticles based on amphiphilic block copolymers as described in claim 1, characterized in that, In step one, the general structural formula of the organic tellurium compound is R. 1 –Te–R 2 ,in: R 1 For C6-C 12 An ester derivative of one or any one of aryl, C1-C6 alkoxy, carboxyl, cyano, or C1-C6 straight-chain or branched alkyl groups; R 2 C1-C6 alkyl, C6-C 12 One of aryl and substituted aryl; The azo initiator is an organic azo initiator.
5. The method for constructing nanoparticles based on amphiphilic block copolymers as described in claim 4, characterized in that, The R 1 It is any one of aryl, ester, carboxyl, cyano, and C1-C6 straight-chain or branched alkyl groups; Wherein, the aryl group is phenyl or p-methoxyphenyl; The R 2 It is one of methyl, ethyl, phenyl, and p-methoxyphenyl; The azo initiator is one of azobisisobutyronitrile, azobisisovalerate, and azobiscyclohexylformitrile.
6. The method for constructing nanoparticles based on amphiphilic block copolymers as described in claim 1, characterized in that, The inert gas mentioned in step one is nitrogen or argon.
7. The method for constructing nanoparticles based on amphiphilic block copolymers as described in claim 1, characterized in that, In step two, the amphiphilic block copolymer solution is added dropwise to deionized water at a stirring temperature of 20-40°C.
8. Nanoparticles prepared by the nanoparticle construction method based on amphiphilic block copolymers as described in any one of claims 1-7, characterized in that, The nanoparticles have a core-shell structure, with a hydrophilic shell and a hydrophobic core; the nanoparticles are spherical in shape and have a particle size of 20~200 nm.
9. An application of the nanoparticles as described in claim 8, characterized in that, By utilizing the responsiveness of the nanoparticles to environmental pH, the particle size changes under different pH conditions, thereby enabling the controlled release of the drug.
10. An application of the nanoparticles as described in claim 8 in drug delivery, characterized in that, When the nanoparticles are encapsulated with hydrophobic drugs, the drug loading efficiency of the nanoparticles is greater than 30%. Among them, the hydrophobic drug is any one of paclitaxel, irinotecan, and coumarin.