Amphiphilic diblock copolymer based on beta-cyclodextrin chain transfer agent as well as synthesis method and application of amphiphilic diblock copolymer

Abstract

The invention discloses an amphiphilic diblock copolymer based on a beta-cyclodextrin chain transfer agent as well as a synthesis method and application of the amphiphilic diblock copolymer. The copolymer takes PDTCD as a macromolecular chain transfer agent, and is copolymerized with a vinyl modified hydrophobic medical polymer (PEG-PCL-Ac, PLA-Ac or PLGA-Ac) through RAFT (Reversible Addition-Fragmentation Chain Transfer) polymerization reaction to form a block structure with self-assembly capability. The copolymer can be self-assembled into polymer quantum dots (QDs) with the particle size smaller than 6 nm in water and shows the aggregation-induced emission (AIE) characteristic, the fluorescence emission peak is located near 470 nm, the quantum yield is larger than or equal to 10%, the fluorescence lifetime is larger than or equal to 200 ns, and the copolymer has excellent light stability and biocompatibility. Experiments show that the fluorescent probe shows low-toxicity and high-contrast fluorescence imaging effects in cell imaging. The invention provides a new thought for the development of a novel fluorescent probe, and can be applied to the fields of early disease diagnosis, drug delivery monitoring, personalized medical treatment and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer materials and biomedicine, and particularly relates to a synthesis method and application of an amphiphilic diblock copolymer based on a beta-cyclodextrin chain transfer agent. Background Art

[0002] Aggregation-induced emission (AIE), named one of the top ten emerging technologies in chemistry in 2020 by the International Union of Pure and Applied Chemistry (IUPAC), describes a phenomenon in which the more aggregated a molecule is, the higher its luminescence efficiency. Because AIE materials effectively overcome the aggregation-quenching phenomenon of traditional fluorescent molecules, they are currently considered one of the most promising new luminescent materials of the future and are widely used in fields such as photoelectric conversion, chemical detection, drug delivery, fluorescence sensing, and fluorescence imaging. However, the structures of currently reported AIE molecules mostly consist of conjugated backbones or π-electron systems connected by covalent bonds. This structure results in these fluorescent polymers suffering from poor photostability, high cytotoxicity, poor water solubility and biocompatibility, and complex synthesis processes, which seriously hinder their widespread application in the biological field. Therefore, the preparation of AIE molecules with good water solubility and excellent biocompatibility is an urgent problem to be solved.

[0003] At the intersection of modern materials science and biomedicine, amphiphilic block polymers can self-assemble in solution to form various nanostructures, such as micelles and vesicles. These nanostructures offer significant advantages in applications such as drug delivery, biosensors, and bioimaging. As a key technology in biomedical research, bioimaging is crucial for early and accurate diagnosis of diseases, monitoring treatment progress, and evaluating therapeutic efficacy. High-resolution, high-sensitivity, and precisely targeted imaging probes have long been a research focus in this field. Amphiphilic block polymers, due to their excellent biocompatibility, structural controllability, and superior performance, are ideal fluorescent imaging probes. Structurally, amphiphilic block polymers are composed of a clever combination of hydrophilic and hydrophobic segments, a unique structure that endows them with a rich array of physicochemical properties. In environments such as selective solvents, they can spontaneously self-assemble into a variety of nanostructures, such as spheres and rods. The research and application of amphiphilic block polymers is currently experiencing a period of rapid development, bringing new opportunities and vitality to innovation in fields such as materials science and biomedicine.

[0004] β-cyclodextrin is a class of oligosaccharides with a unique cyclic structure. Its hydrophobic interior and hydrophilic exterior allow for inclusion complexation with a variety of guest molecules, a property that holds broad application prospects in materials science and biomedicine. Introducing β-cyclodextrin as a chain transfer agent in the design and synthesis of amphiphilic block polymers not only imparts novel functional properties but also allows for further manipulation of their self-assembly behavior and biocompatibility.

[0005] The present invention uses the homopolymer PDTCD containing a dithioester structure as a macromolecular chain transfer agent, screens three commercial medical polymer materials containing strongly hydrophobic segments: PLA, PLGA, and PEG-PCL, and performs vinyl modification to synthesize the corresponding polymerization-active monomers PEG-PCL-Ac, PLA-Ac, and PLGA-Ac. A series of amphiphilic diblock copolymers containing short polyamine β-CD chains and controllable chain lengths are then synthesized using the RAFT method: PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA, endowed with self-assembly capabilities. The self-assembly morphology, AIE performance, and optical stability of the three copolymers are systematically studied. Microscopic morphology tests revealed that the three block copolymers all exhibited quasi-spherical structures after self-assembly, with average particle sizes within 6 nm, exhibiting good dispersibility and morphological stability, thus demonstrating that the three block copolymers can generate polymer QDs through self-assembly. Optical test results show that PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGAQDs all have typical AIE luminescence properties, with the strongest fluorescence emission peak located near 470nm, and exhibit excellent luminescence stability and light stability. Finally, bioluminescence imaging results show that PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGAQDs all have low cytotoxicity and good fluorescence imaging effects. Therefore, this invention not only opens up a new path for the development of new fluorescent probes, but also can play an important role in fields such as early disease diagnosis, drug delivery monitoring, and personalized medicine. Summary of the Invention

[0006] The present invention aims to provide an amphiphilic diblock copolymer based on a β-cyclodextrin chain transfer agent (PDTCD), polymer quantum dots (QDs) formed by self-assembly thereof, and application thereof in bioluminescence imaging.

[0007] 1. Amphiphilic diblock copolymers and their synthesis The present invention is an amphiphilic diblock copolymer based on a β-cyclodextrin chain transfer agent. It uses a β-cyclodextrin homopolymer (PDTCD) containing a dithioester structure as a macromolecular chain transfer agent, and is formed by initiating the polymerization of hydrophobic medical polymer monomers containing terminal vinyl groups through a RAFT polymerization reaction. The copolymer can self-assemble in water to form polymer quantum dots (QDs).

[0008] The hydrophobic medical polymer monomer containing a vinyl group at the end is selected from at least one of the following: vinyl-modified polyethylene glycol-polycaprolactone (PEG-PCL-Ac); vinyl-modified polylactide-glycolic acid polymer (PLA-Ac); Vinyl-modified poly(lactide-polyglycolide-glycolic acid) polymer (PLGA-Ac).

[0009] The dithioester-containing β-cyclodextrin homopolymer PDTCD is prepared from a vinyl monomer (DTCD-Ac) derived from β-cyclodextrin through RAFT polymerization.

[0010] The method for synthesizing the amphiphilic diblock copolymer of the present invention comprises the following steps: (1) PDTCD, a hydrophobic medical polymer monomer containing a vinyl group at the end (PEG-PCL-Ac, PLA-Ac, or PLGA-Ac), and an initiator AIBN were dissolved in N,N-dimethylformamide (DMF) and subjected to RAFT polymerization under vacuum at 60-80°C for 4-6 h; the mass ratio of PDTCD to the hydrophobic medical polymer monomer containing a vinyl group at the end was 1:1-3:1.

[0011] (2) After the reaction is completed, the mixture is cooled to room temperature, precipitated with acetone, centrifuged and vacuum dried to obtain copolymers PDTCD-PEG-PCL, PDTCD-PLA or PDTCD-PLGA; the synthetic route of the amphiphilic diblock copolymer is as follows: Figure 1 .

[0012] (3) The copolymer is dissolved in water and self-assembled to form polymer quantum dots PDTCD-PEG-PCL QDs, PDTCD-PLA QDs or PDTCD-PLGA QDs. The concentration of the copolymer self-assembled in water is ≥1×10 -3 mg / mL.

[0013] The method for synthesizing the dithioester-containing β-cyclodextrin homopolymer (PDTCD) comprises the following steps: (1) Synthesis of CD-OTS: Under alkaline conditions, β-cyclodextrin and p-toluenesulfonyl chloride were reacted at 0-5°C for 4-6 hours, and the sulfonylated product (CD-OTS) was obtained after purification; the molar ratio of β-cyclodextrin to p-toluenesulfonyl chloride was 1:0.8-1.0; (2) Synthesis of DTCD: CD-OTS and diethylenetriamine were dissolved in anhydrous N-methylpyrrolidone and reacted at 60-80°C for 7-8 hours under the catalysis of potassium iodide. After precipitation and purification, a linear polyamine short-chain modified β-cyclodextrin derivative (DTCD) was obtained; the molar ratio of CD-OTS to diethylenetriamine was 1:3-4; (3) Synthesis of DTCD-Ac: Using anhydrous N, N-dimethylformamide as solvent, DTCD and methacrylic acid were activated by esterification with dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (HoSU) to produce β-cyclodextrin-derived vinyl monomer (DTCD-Ac). The esterification reaction was carried out in two stages: first at 0-5°C for 1-2 h, then at room temperature for 35-40 h. The molar ratio of DTCD to methacrylic acid was 1:1-1.5. (4) Synthesis of homopolymer PDTCD: Using N,N-dimethylformamide as solvent, 4-cyano-4-(thiobenzoylthio)valeric acid as chain transfer agent, and azobisisobutyronitrile (AIBN) as initiator, DTCD-Ac monomer was converted into β-cyclodextrin homopolymer (PDTCD) containing a dithioester structure through RAFT polymerization reaction; the conditions of RAFT polymerization reaction were: molar ratio of DTCD-Ac to chain transfer agent was 1:0.8~1.2, reaction temperature was 60~80℃, and reaction time was 4~6h.

[0014] The synthesis method of the hydrophobic medical polymer monomer containing vinyl groups at the end comprises: PEG-PCL-Ac: Polyethylene glycol-polycaprolactone (PEG-PCL) and methacryloyl chloride are reacted in tetrahydrofuran (THF) with triethylamine as a base at room temperature for 20-25 h. The molar ratio of methacryloyl chloride to PEG-PCL is 100:1-50:1. PLA-Ac: Ring-opening polymerization of lactide and 2-hydroxyethyl methacrylate at 110-130°C for 15-20 h in the presence of stannous octoate. The mass ratio of lactide to 2-hydroxyethyl methacrylate is 20:1-25:1. PLGA-Ac: PLA-Ac and glycolide are copolymerized under the catalysis of stannous octoate. The reaction is carried out under argon protection at a temperature of 110-130°C for 10-15 hours. The mass ratio of PLA-Ac to glycolide is 1:3-1:4.

[0015] 2. Characterization and Properties of Amphiphilic Diblock Copolymers 1. Molecular weight characterization of amphiphilic diblock copolymers The molecular weight of PDTCD-PCL-Ac, PLA-Ac, PLGA-Ac and amphiphilic diblock copolymers PDTCD-PEG-PCL, PDTCD-PLA and PDTCD-PLGA containing vinyl hydrophobic segments was tested by gel permeation chromatography (GPC). DMF was used as the mobile phase and polystyrene was used as the standard. The test results are shown in Figure 2. Figure 10 As shown, the GPC elution curve of the polymer is a single peak, wherein the number average molecular weight (M n ) is 2.8×10 4 , weight average molecular weight (M w ) is 3.0×10 4 Calculations show that the PDI is 1.08, indicating a very narrow molecular weight distribution, consistent with the characteristics of RAFT-activated polymerization. Calculations of the number-average molecular weight show that the degree of polymerization of the hydrophilic segment in PDTCD-PEG-PCL is 8, while the degree of polymerization of the hydrophobic segment is 3.

[0016] 2. Critical micelle concentration of amphiphilic diblock copolymers The critical micelle concentration (CMC) of a copolymer refers to the minimum concentration at which the copolymer molecules in a solution begin to form micelles under certain conditions. When the copolymer concentration is lower than the CMC, they are dispersed in the solvent as single molecules or small aggregates. When the concentration reaches or exceeds the CMC, the hydrophobic portions of the copolymer molecules aggregate with each other, while the hydrophilic portions face the solvent, forming micelles. This paper uses pyrene as a fluorescent probe and uses a fluorescence spectrophotometer to determine the CMC value of polymer micelles. The excitation wavelength is set to 334 nm and the I 392 / I 372 The fluorescence intensity at the two locations is plotted as the ordinate, and the logarithm of the concentration of the amphiphilic diblock copolymer (Log C) is plotted as the abscissa. Figure 11 As shown in (a, c, e), the characteristic peak intensity of pyrene increases significantly with the increase of concentration. Figure 11 (b, d, f) show that the critical micelle concentrations of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA are 9.1×10 -4 mg / mL, 9.28×10 -4 mg / mL、8.1×10 -5 Based on this experimental result, the concentration needs to be controlled above this CMC value in subsequent self-assembly experiments.

[0017] 3. Self-assembly morphology of amphiphilic diblock copolymers According to the CMC values ​​of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA, we selected a concentration of 1×10 -3 Self-assembly experiments were conducted using aqueous solutions of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA at 100 mg / mL. After ultrasonic treatment, the copolymer solution was pipetted onto an ultrathin carbon film using a rubber-tipped pipette. The solvent was completely evaporated at a constant temperature, and the morphology of the copolymer sample was observed using TEM.

[0018] Depend on Figure 12 As shown, PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA all self-assembled in aqueous solution to form nanospherical particles with average particle sizes of 4-5 nm, 5-6 nm, and 3-4 nm, respectively. They exhibited excellent dispersibility and exhibited no agglomeration. This is because, in the three copolymers, PDTCD and PEG are hydrophilic, while PCL, PLA, and PLGA are hydrophobic, giving them an amphiphilic structure and thus enabling self-assembly. Furthermore, the polymer chains of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA all contain numerous hydroxyl (-OH) and amino (-NH2) groups, which can form strong hydrogen bonds within and between the molecular chains, further enhancing their self-assembly ability. This contributes to the formation of stable nanospherical structures, resulting in very small particle sizes. The above test results show that the three amphiphilic diblock copolymers PDTCD-PEG-PCL, PDTCD-PLA and PDTCD-PLGA all have strong self-assembly ability and can be assembled to form polymer QDs materials with a particle size of less than 6 nm.

[0019] In addition, in order to determine the elemental composition of PDTCD-PEG-PCL, PDTCD-PLA and PDTCD-PLGA QDs, their SEM-EDS spectra were tested respectively. The test results showed that all three polymer QDs contained C, O, N and S elements ( Figure 13 (a, b), Figure 14 (a, b) and Figure 15 (a, b)). In addition, the EDS elemental spectra of the three ( Figure 13 (c) Figure 14 (c) and Figure 15 (c) It can be observed that the four elements C, O, N, and S on the polymer are evenly distributed throughout the sample.

[0020] 6. Optical properties of amphiphilic diblock copolymers In addition, the solid quantum yield (QY) and fluorescence lifetime (τ) of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs were also measured, and the test results are listed in Table 2. The QY of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs in water were 14%, 29%, and 17%, respectively. At the same time, the average fluorescence lifetime of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs in water were 242 ns, 225 ns, and 369 ns, respectively. Figure 16 Compared with traditional π-conjugated organic fluorescent dyes, the fluorescence lifetime is increased by 1-2 orders of magnitude, effectively making up for the short fluorescence lifetime of traditional luminescent materials.

[0021] When the solvent has good solubility for one of the fragments but poor solubility for the other fragment, a selective solvent effect will occur. Next, the fluorescence changes of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs in solvents of different polarity were studied. Commonly used organic reagents in the laboratory: dichloromethane (DCM), tetrahydrofuran (THF), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and other solvents were selected for testing. Figure 17 As shown in (a, b, c), under the same concentration conditions, PDTCD-PEG-PCL QDs in HO exhibit not only high fluorescence intensity but also ideal peak shape. Furthermore, solvent screening using the same method for PDTCD-PLA QDs and PDTCD-PLGA QDs revealed that DMF exhibited the strongest fluorescence emission. Therefore, the highly polar solvents DMSO and DMF are the optimal solvents for PDTCD-PEG-PCL, PDTCD-PLA QDs, and PDTCD-PLGA QDs, respectively, in fluorescence testing.

[0022] 7. AIE properties of amphiphilic diblock copolymers (1) Testing the AIE effect by adding a poor solvent Water (H2O) was selected as the good solvent and acetonitrile (ACN) as the poor solvent for the AIE effect test. The changes in the fluorescence intensity of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs and PDTCD-PLGA QDs in mixed solutions with different H2O / ACN volume ratios (9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9) at the same concentration were tested. Figure 18 (a, b) are the fluorescence spectra of PDTCD-PEG-PCL QDs in mixed solutions with different H2O / ACN volume ratios and the corresponding change curves. As can be seen from the figure, when the volume fraction of the poor solvent ACN is in the range of 0%-20%, PDTCD-PEG-PCL QDs emit weak fluorescence. This is mainly because the polymer molecules exist in a single-molecule dispersed state in the mixed system, and there is no formation of a large number of aggregates. The interactions between O...O, N...N and O...N between molecules are weak, and it is impossible to construct a three-dimensional electronic interaction channel and form an effective spatial conjugated system. Therefore, the detected fluorescence signal is weak. When the volume ratio of the poor solvent ACN is greater than 20%, the solubility of PDTCD-PEG-PCLQDs drops sharply, and a large number of PDTCD-PEG-PCL QDs aggregates are formed in the system. The interactions between O...O, N...N and O...N between molecules are enhanced, and a three-dimensional electronic interaction channel is constructed to form an effective spatial conjugated system. The molecular rigidity is also enhanced, so the fluorescence intensity undergoes a turning point change and is significantly enhanced. The above-mentioned luminescence enhancement trend can be observed with the naked eye ( Figure 18 The above experimental results demonstrate that PDTCD-PEG-PCL QDs possess typical AIE properties.

[0023] like Figure 18 (c, d) are the fluorescence spectra of PDTCD-PLA QDs in mixed solutions with different H2O / ACN volume ratios and the corresponding change curves. We observed that as the volume fraction of the poor solvent continued to increase, the corresponding fluorescence intensity also gradually increased. This is attributed to the addition of the poor solvent ACN, which reduced the solubility of PDTCD-PLA QDs and formed a large number of PDTCD-PLAQDs aggregates in the system. The intermolecular O...O, N...N and O...N interactions were enhanced, constructing a three-dimensional electronic interaction channel and forming an effective spatial conjugated system. The molecular rigidity was also enhanced, resulting in a turning point in the fluorescence intensity. The above luminescence enhancement trend can be observed with the naked eye ( Figure 18 The above experimental results demonstrate that PDTCD-PLA QDs possess typical AIE properties.

[0024] like Figure 18(e, f) are the fluorescence spectra of PDTCD-PLGA QDs in mixed solutions with different H2O / ACN volume ratios and the corresponding change curves. We observed that as the volume fraction of the poor solvent continued to increase, the corresponding fluorescence intensity also gradually increased. This is attributed to the addition of the poor solvent ACN, which reduced the solubility of PDTCD-PLGA QDs and formed a large number of PDTCD-PLGA QDs aggregates in the system. The intermolecular O...O, N...N and O...N interactions were enhanced, and a three-dimensional electronic interaction channel was constructed to form an effective spatial conjugated system. The molecular rigidity was also enhanced, so the fluorescence intensity underwent a turning point change and was significantly enhanced. The above-mentioned luminescence enhancement trend can be observed with the naked eye ( Figure 18 The above experimental results demonstrate that PDTCD-PLGA QDs possess typical AIE properties.

[0025] 3. Application of Amphiphilic Diblock Copolymers 1. Cellular Fluorescence Imaging of Amphiphilic Diblock Copolymers In the study of biological fluorescent probes, cytotoxicity evaluation is an important indicator for investigation before fluorescent probes are used for cell imaging experiments. The present invention uses the MMT method to test the cell activity of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs and PDTCD-PLGA QDs at concentrations of 20 μg / mL, 40 μg / mL, 60 μg / mL, 80 μg / mL and 100 μg / mL in three tumor cells (Hela, MKN-45 and Hep-G2 cells) after incubation for 12 hours. The test results show that ( Figure 19 When the concentration of PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs solutions reached 100 μg / mL, their survival rates in all three cell types remained above 95%, indicating that PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs have low cytotoxicity and good biocompatibility. Based on this, further cell imaging experiments can be carried out.

[0026] Subsequently, based on the advantages of PDTCD-PEG-PCL QDs such as excellent optical properties and low cytotoxicity, the application of bioimaging was further studied. First, the cell imaging effect of PDTCD-PEG-PCL QDs at the same concentration and different incubation time conditions was studied. Figure 20 Hela, MKN-45 and Hep-G2 cells were added to 12-well plates and incubated in culture medium containing 100 μg / mL PDTCD-PEG-PCL QDs for 1 h, 2 h, 4 h and 8 h. Figure 20(a) It can be seen that PDTCD-PEG-PCL QDs can enter Hela cells through cellular endocytosis, and the fluorescence signal continues to increase with the increase of incubation time. After 1 h of co-incubation, a certain amount of PDTCD-PEG-PCLQDs entered the cells, and green fluorescence signals could be observed in the three tumor cells. As the incubation time prolonged, more PDTCD-PEG-PCL QDs samples could be observed entering the tumor cells at 2 h, and the fluorescence signal was enhanced compared to 1 h. After another 4 h of incubation, the fluorescence brightness in the cells was significantly enhanced. After incubation for 8 h, the fluorescence signal intensity in the cells did not increase significantly, indicating that after 4 h of staining, PDTCD-PEG-PCL QDs had reached the maximum degree of aggregation in the cells. The above studies show that PDTCD-PEG-PCLQDs can enter tumor cells through endocytosis and are enriched in tumor cells within a certain period of time, causing their fluorescence signal intensity to gradually increase. PDTCD-PLAQDs ( Figure 21 ) and PDTCD-PLGAQDs ( Figure 22 ) also showed a similar growth trend over time.

[0027] 2. Imaging of Multicellular 3D Tumor Microspheres Using Amphiphilic Diblock Copolymers The present invention uses multicellular tumor spheroids to evaluate the tumor penetration ability and imaging effect of polymer QDs. The study selected PDTCD-PEG-PCL QDs as a representative QD and MKN-45 cells as a model. Figure 23The migration and penetration patterns of PDTCD-PEG-PCL QDs within tumor spheroids at different times are shown, demonstrating the temporal trend of PDTCD-PEG-PCL QD penetration within multicellular tumor spheroids. As shown in the figure, from 3 to 24 hours, PDTCD-PEG-PCL QDs exhibit a time-dependent, outward-to-inward penetration pattern within the multicellular tumor spheroids. During the first 12 hours, green fluorescent spots in the confocal images indicate that PDTCD-PEG-PCL QDs are primarily concentrated in the outer regions of the 3D model. Over time, the fluorescence signal in the inner regions of the model gradually increases, indicating a continuous increase in the number of QDs penetrating the tumor spheroids. After 24 hours of culture, PDTCD-PEG-PCL QDs have penetrated almost to the center of the 3D spheroids. This demonstrates the excellent tumor-penetrating ability of PDTCD-PEG-PCL QDs, which can evenly penetrate the interior of 3D MCTS, reaching the necrotic region. This effectively overcomes the problem of poor penetration depth of QDs in in vitro spheroid models. These results demonstrate that PDTCD-PEG-PCL QDs exhibit excellent tumor penetration and have great potential as fluorescent probes for internal tumor analysis.

[0028] In summary, the present invention first designed and synthesized the vinyl monomer DTCD-Ac, based on the linear polyamine short-chain β-CD. A β-CD homopolymer, PDTCD, containing a terminal dithioester structure, was synthesized using the RAFT living polymerization method. Using PDTCD as a macromolecular chain initiator, three commercially available polymers, PLA, PLGA, and PEG-PCL, were vinyl-modified. Subsequently, RAFT copolymerization with PDTCD was achieved. The resulting amphiphilic diblock copolymers containing β-CD polymer chains and controllable chain lengths: PDTCD-PLA, PDTCD-PLGA, and PDTCD-PEG-PCL, were successfully synthesized, endowing PDTCD with enhanced self-assembly capabilities. The self-assembly morphology, optical properties, and stability of the three amphiphilic diblock copolymers were systematically investigated. Microscopic morphological tests demonstrated that PDTCD-PLA, PDTCD-PLGA, and PDTCD-PEG-PCL all exhibited strong self-assembly capabilities. They assembled in aqueous solution to form regular spherical nanoparticles with an average particle size of less than 6 nm, exhibiting good dispersibility and morphological stability, demonstrating the formation of polymer QDs. Optical test results show that PDTCD-PLAQDs, PDTCD-PLGAQDs, and PDTCD-PEG-PCL QDs have typical AIE luminescence characteristics, with emission wavelengths located near 470nm, fluorescence quantum yields of 14%, 29%, and 17%, respectively, and fluorescence lifetimes of 242ns, 225ns, and 369ns, respectively, which make up for the short fluorescence lifetime of traditional luminescent materials. In addition, the results of cell confocal fluorescence imaging experiments showed that by staining Hela, MKN-45, and Hep-G2 tumor cells, the three QDs exhibited bright green fluorescence signals in the cells. The results of 3D tumor microsphere (MCTS) imaging studies showed that the polymer QDs synthesized using this method can successfully penetrate into the interior of 3D tumor microspheres and ultimately reach the necrotic area, thus effectively overcoming the current application problem of insufficient penetration depth of fluorescent probes into tumor microspheres. In summary, PDTCD-PLAQDs, PDTCD-PLGAQDs, and PDTCD-PEG-PCL QDs all have application advantages such as excellent luminescence performance, low cytotoxicity, good biocompatibility, and good biological imaging effect.

[0029] The present invention has the beneficial effects of using PDTCD as a macromolecular chain transfer agent to initiate polymerization of three terminal vinyl-containing bioactive polymer monomers (PEG-PCL-Ac, PLA-Ac, and PLGA-Ac) via RAFT polymerization to prepare a series of amphiphilic block copolymers with controllable chain lengths and terminal dithioester structures. These copolymers, PDTCD-PLA, PDTCD-PLGA, and PDTCD-PEG-PCL, impart enhanced self-assembly capabilities to PDTCD. The homopolymer PDTCD forms copolymers by combining with hydrophobic segments of varying structures. Because the copolymers contain both hydrophilic and hydrophobic portions, the hydrophobic segments aggregate in close proximity in water due to the repulsive force of water molecules, promoting the formation of spherical structures with a hydrophobic interior and a hydrophilic exterior. Furthermore, the hydrophilic groups form hydrogen bonds, stabilizing the distribution of the hydrophilic segments on the spherical surface and promoting the self-assembly of the PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA segments. The results showed that all three block copolymers possessed excellent self-assembly capabilities in water, forming three types of polymer QDs with particle sizes less than 6 nm: PDTCD-PEG-PCL QDs, PDTCD-PLA QDs, and PDTCD-PLGA QDs. Furthermore, the three polymer QDs exhibited typical AIE luminescence properties, emitting strong fluorescence at approximately 470 nm, with fluorescence quantum yields exceeding 10% and fluorescence lifetimes exceeding 200 ns. In 3D tumor microsphere (MCTS) imaging studies, these polymer QDs successfully penetrated the interior of the 3D tumor microspheres and ultimately reached the necrotic areas, effectively overcoming the current application problem of insufficient penetration depth of fluorescent probes into tumor microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 Schematic diagram of the synthetic route of amphiphilic diblock copolymers; Figure 2 H NMR spectrum of PDTCD; Figure 3 H NMR spectrum of PEG-PCL; Figure 4 H NMR spectrum of PEG-PCL-Ac; Figure 5 H NMR spectrum of PDTCD-PEG-PCL; Figure 6 H NMR spectrum of PLA-Ac; Figure 7 H NMR spectrum of PDTCD-PLA; Figure 8 H NMR spectrum of PLGA-Ac; Figure 9 H NMR spectrum of PDTCD-PLGA; Figure 10 Gel permeation chromatogram of amphiphilic diblock copolymer; Figure 11 (a, c, e) Fluorescence spectra of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA in pyrene solution; (b, d, f) Fluorescence intensity ratio (I392 / I372) versus the logarithm (Log C) of the concentrations of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA; Figure 12 (a, b, c) TEM images of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA; (d, e, f) Particle size distribution of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA (Inset: path diagram of the block copolymer irradiated by a laser pointer under sunlight); Figure 13 (a, b) SEM-EDS analysis and (c) EDS elemental map of PDTCD-PEG-PCL QDs. Figure 14 (a, b) SEM-EDS analysis and (c) EDS elemental mapping of PDTCD-PLA QDs. Figure 15 (a, b) SEM-EDS analysis and (c) EDS elemental mapping of PDTCD-PLGA QDs. Figure 16 Fluorescence lifetime of (a) PDTCD-PEG-PCL (b) PDTCD-PLA (c) PDTCD-PLGA QDs; Figure 17 Fluorescence spectra of (a) PDTCD-PEG-PCL QDs, (b) PDTCD-PLA QDs, and (c) PDTCD-PLGA QDs in different solvents. Figure 18 (a, c, e) Fluorescence emission spectra of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA QDs solutions with different volume fractions of ACN; (b, d, f) Dotted line graphs of fluorescence intensity of PDTCD-PEG-PCL, PDTCD-PLA, and PDTCD-PLGA QDs solutions with different volume fractions of ACN; Figure 19 Cytotoxicity tests of (a) PDTCD-PEG-PCL, (b) PDTCD-PLA, and (c) PDTCD-PLGA QDs in Hela, MKN-45, and Hep-G2 cells after incubation at different concentrations for 12 h. Figure 20 (a) Imaging of Hela cells; (b) Imaging of MKN-45 cells; (c) Imaging of Hep-G2 cells after incubation with 100 μg / mL PDTCD-PEG-PCL QDs for 1 h, 2 h, 4 h, and 8 h. Figure 21 (a) Imaging images of Hela cells; (b) Imaging images of MKN-45 cells; (c) Imaging images of Hep-G2 cells after incubation with 100 μg / mL PDTCD-PLA QDs for 1 h, 2 h, 4 h, and 8 h. Figure 22 (a) Imaging images of Hela cells after incubation with 100 μg / mL PDTCD-PLGA QDs for 1 h, 2 h, 4 h, and 8 h; (b) Imaging images of MKN-45 cells; (c) Imaging images of Hep-G2 cells; Figure 23 Fluorescence expression of PDTCD-PEG-PCL QDs in 3D MKN-45 cell microspheres at different times (scale bar: 400 μm); Figure 24 H NMR spectrum of CD-OTS; Figure 25 H NMR spectrum of DTCD; Figure 26 H NMR spectrum of DTCD-Ac. DETAILED DESCRIPTION

[0031] The synthesis method of the amphiphilic diblock copolymer of the present invention is described in detail below through specific embodiments.

[0032] Example 1 Synthesis of PDTCD (1) Synthesis of CD-OTS β-cyclodextrin (β-CD, 10 g, 8.8 mmol) was added to a 500 mL three-necked flask, followed by stirring and dissolving in sodium hydroxide solution (200 g, 0.75 mol / L). The reaction temperature was controlled between 0 and 5°C, and p-toluenesulfonyl chloride (TsCl, 3.36 g, 7.6 mmol) was slowly added dropwise. After 5 h of reaction, the unreacted p-toluenesulfonyl chloride was separated by filtration through a fritted funnel. The filtrate was adjusted to pH 7 with 10% hydrochloric acid and refrigerated. The crude product was then filtered through a fritted funnel again. The crude product was dissolved in boiling water and then hot filtered to remove impurities. The filtrate was refrigerated again, filtered, and dried for 8 h to obtain the product, CD-OTS, in a yield of approximately 51%.

[0033] 1H NMR (400 MHz, DMSO-d6) δ: 7.74 (s, 1H), 7.45 (s, 1H), 5.72 (s,13H), 4.85 (s, 4H), 4.77 (s, 2H), 4.39 (s, 1H), 4.31 (s,1H), 3.58 (s, 15H),3.51 (s, 4H), 2.43 (s, 3H), such as Figure 24 。ESI-MS: m / z calcd for C 49 H 77 O 37 S [M+H] + ,1289.5081, found:1289.5083.

[0034] (2) Synthesis of DTCD The prepared CD-OTS (2.0 g, 1.55 mmol) was dissolved in anhydrous N-methylpyrrolidone (10 mL). Solid potassium iodide (0.025 g, 0.15 mmol) and diethylenetriamine (0.54 mL, 5 mmol) were added with stirring and the reaction was carried out at 70°C for 8 h. After the reaction, the solution was cooled to room temperature and precipitated with anhydrous ethanol. The precipitate was collected by vacuum filtration. The resulting crude product was dissolved in a mixture of water and methanol (1:3 by volume) and precipitated with acetone. After centrifugation and drying, the white product DTCD was obtained in a yield of 42%.

[0035] 1 H NMR (400 MHz, DMSO-d6) δ: 4.82 (s, 7H), 4.53 (s, 11H), 3.82–3.42(m, 17H), 3.42–3.13 (m, 13H), 2.69 (d, J = 0.7 Hz, 4H), 2.56 (s, 4H), 2.29 (s,1H), 2.18 (s, 3H), such as Figure 25 。ESI-MS: m / z calcd for C 46 H 82 O 34 N3[M+H] + ,1220.4711,found: 1220.4711.

[0036] (3) Synthesis of monomer DTCD-Ac Methacrylic acid (0.129 g, 1.5 mmol) and dicyclohexylcarbodiimide (DCC, 0.309 g, 1.5 mmol) were dissolved in 30 mL of anhydrous N,N-dimethylformamide and stirred at room temperature for 20 min. N-hydroxysuccinimide (HoSU, 0.19 g, 1.65 mmol) and DTCD (1.342 g, 1.1 mol) were then added and reacted at 0°C for 1 h. The reaction was then warmed to room temperature and continued for 36 h. After completion of the reaction, the reaction solution was filtered, the supernatant collected, and precipitated with acetone. DTCD-Ac was obtained by suction filtration and drying to obtain a white solid. The yield was approximately 30%.

[0037] 1 H NMR (400 MHz, DMSO-d6) δ: 7.95 (s, 3H), 5.71 (d, J = 16.1 Hz, 16H),4.83 (s, 8H), 3.76–3.15(m, 31H), 2.89 (s, 11H), 2.73 (s, 9H), 2.55 (d, J =34.2 Hz, 6H), 1.85 (s, 3H), as Figure 26 。ESI-MS: m / z calcd for C 50 H 86 O 35 N3[M+H] + ,1288.5052,found:1288.5053.

[0038] (4) Synthesis of homopolymer PDTCD DTCD-Ac (0.49 g, 0.38 mmol) was dissolved in 10 mL of DMF. Then, under nitrogen, 4-cyano-4-(thiobenzoylthio)valeric acid (0.0097 g, 0.35 mmol) and azobisisobutyronitrile (0.00049 g, 0.0029 mmol) were added. The mixture was heated to 70°C for 5 h. After the reaction, the solution was precipitated with acetone and centrifuged to obtain PDTCD as a white solid in an approximately 15% yield.

[0039] 1H NMR (400 MHz, DMSO-d6) δ: 7.68 (s,1H), 7.44 (s, 2H), 7.11 (s, 2H),5.77 (s, 201H), 4.81 (s, 131H), 3.62 (s, 366H),3.29 (s, 345H), 2.71 (s, 39H),2.61 (s, 74H), 2.27 (s, 2H), 1.57 (s, 5H). Figure 2 .

[0040] The synthetic route of PDTCD is as follows: .

[0041] Example 2 Synthesis of amphiphilic diblock copolymer PDTCD-PEG-PCL (1) Synthesis of polyethylene glycol-polycaprolactone (PEG-PCL) Polyethylene glycol monomethyl ether (20 g, 0.01 mol, M w =2000) and 15 mL of freshly distilled ℇ-caprolactone (ℇ-CL) were added to a 100 mL round-bottom flask, and stannous octoate (Sn(oct) 2， The reaction mixture (0.4 mmol, 0.16 g) was reacted at 140°C for 6 h and cooled to a light brown solid. The solid was then dissolved in dichloromethane and precipitated with ether to produce a large amount of white flocculent precipitate. The precipitate was dried in a vacuum oven to obtain the product polyethylene glycol-polycaprolactone (PEG-PCL) in approximately 80% yield.

[0042] 1 H NMR (400 MHz, Chloroform-d), δ4.22 (s, 1H), 4.05 (t, J=6.7 Hz, 28H), 3.64 (s, 64H), 3.49 (s, 3H), 2.30 (s, 30H), 1.70-1.58 (m, 62H),1.43-1.31 (m,32H), such as Figure 3 .

[0043] (2) Synthesis and characterization of polyethylene glycol-polycaprolactone derivatives (PEG-PCL-Ac) To a three-necked flask, 2.0 g of PEG-PCL, triethylamine (8.4 mL, 60 mmol), and 100 mL of anhydrous tetrahydrofuran (THF) were added and stirred at 0°C for 30 min. Then, 40 mL of a THF solution of methacryloyl chloride (1.5 mL, 30 mmol) was slowly added dropwise. The mixture was allowed to react at room temperature for 24 h. Precipitation with methanol yielded a large amount of white precipitate. After centrifugation and filtration, the solid precipitate was dried in a vacuum oven for 24 h to obtain the product, PEG-PCL-Ac, with a yield of approximately 65%.

[0044] 1 H NMR (400 MHz, Chloroform-d), δ=6.09 (s, 1H), 5.55 (s, 1H), 4.05 (s, 61H), 3.64 (s, 114H), 3.49 (s, 4H), 2.30 (s, 65H), 1.93 (s, 3H), 1.64 (s,165H), 1.38 (d, J=24.2 Hz, 95H), such as Figure 4 .

[0045] (3) Synthesis of amphiphilic block product PDTCD-PEG-PCL 0.50 g of the macromolecular chain transfer agent PDTCD, 0.25 g of PEG-PCL-Ac, 0.005 g of azobisisobutyronitrile (AIBN, 0.03 mmol), and 50 mL of N,N-dimethylformamide (DMF) were added to a 100 mL three-necked flask and polymerized under vacuum at 70°C for 5 h. After the reaction, the brown reaction solution was cooled to room temperature and precipitated with 200 mL of acetone, yielding a large amount of flocculent precipitate. Centrifugation afforded a white precipitate, which was then dried under vacuum to yield the amphiphilic diblock copolymer PDTCD-PEG-PCL in approximately 68% yield.

[0046] 1 H NMR (400 MHz, Chloroform-d), δ=8.02 (s, 1H),7.84 (s, 1H), 7.62 (s,1H), 7.13 (s, 2H), 4.80 (s, 12H), 4.03 (d, J=6.7 Hz, 12H), 3.61 (s, 20H),3.43 (s, 46H), 2.77 (s, 1H), 2.60 (s, 160H), 2.28 (s,19H), 1.99 (s, 7H), 1.62(s, 27H), 1.35 (s, 14H), 1.22 (s, 5H), such as Figure 5 .

[0047] (4) Preparation of polymer quantum dots: The concentration is 1×10 -3 A PDTCD-PEG-PCL aqueous solution at a concentration of 100 mg / mL was ultrasonically treated, and the homopolymer aqueous solution was pipetted using a rubber-tipped dropper and dropped onto an ultra-thin carbon film. The film was then heated at a constant temperature (25°C) to completely evaporate the solvent, thereby obtaining polymer quantum dots PDTCD-PEG-PCL QDs.

[0048] Example 3 Synthesis of amphiphilic diblock copolymer PDTCD-PLA (1) Synthesis and characterization of polylactide derivatives (PLA-Ac) Lactide (1.44 g, 0.01 mol) purified by recrystallization was added to a 50 mL round-bottom flask. 2-Hydroxyethyl methacrylate (65 mg, 5 mmol) and stannous octoate (Sn(oct)2, 75 mg, 0.185 mmol) were slowly added dropwise. Under argon protection, the mixture was reacted in a 120°C oil bath for 20 h. After the reaction, the reaction solution was cooled to room temperature and precipitated with 200 mL of acetone, yielding a large amount of flocculent precipitate. Centrifugation afforded a white precipitate, which was then dried in vacuo at 40°C to afford PLA-Ac, a vinyl-terminated polymer, in a yield of approximately 56%.

[0049] 1 H NMR (400 MHz, Chloroform-d), δ=6.12 (s, 1H),5.60 (s, 1H), 5.16 (d,J=7.1 Hz, 33H), 4.36 (d, J=6.1 Hz, 6H), 1.95 (d, J=8.5 Hz, 3H), 1.58 (d, J=7.1 Hz, 100H), such as Figure 6 .

[0050] (2) Synthesis and characterization of amphiphilic block product PDTCD-PLA 0.50 g of the macromolecular chain transfer agent PDTCD, 0.25 g of the vinyl monomer PLA-Ac, 0.005 g of the initiator AIBN (0.03 mmol), and 50 mL of N,N-dimethylformamide (DMF) solvent were added to a 100 mL three-necked flask and subjected to RAFT polymerization at 70°C for 5 h under vacuum. After the reaction, the yellow reaction solution was cooled to room temperature and added to 200 mL of acetone for precipitation, resulting in a large amount of flocculent precipitate. A white precipitate was obtained by centrifugation and finally dried in vacuum at 40°C to obtain the amphiphilic diblock copolymer PDTCD-PLA in approximately 78% yield.

[0051] 1 H NMR (400 MHz, DMSO-d6), δ=7.95 (s, 52H), 7.80-7.71 (m, 1H), 7.46(dd, J=16.0, 8.1 Hz, 2H), 7.11 (d, J=7.9 Hz, 1H), 5.83–5.65 (m, 17H), 4.84(s, 7H), 4.34 (s, 4H), 3.62 (d,J=26.1 Hz, 23H), 3.43-3.24 (m, 52H), 2.92-2.86(m, 205H), 2.73 (d, J=0.7 Hz, 186H), 2.25-2.22 (m, 2H), 2.08 (s, 539H), 1.94-1.89 (m, 11H), e.g. Figure 7 .

[0052] (3) Preparation of polymer quantum dots: The concentration is 1×10 -3 A PDTCD-PLA aqueous solution with a concentration of 100 mg / mL was ultrasonically treated, and the homopolymer aqueous solution was pipetted using a rubber-tipped dropper and dropped onto an ultra-thin carbon film. The solution was heated at a constant temperature (25°C) to completely evaporate the solvent, thereby obtaining polymer quantum dots PDTCD-PLA QDs.

[0053] Example 4 Synthesis and Characterization of Amphiphilic Diblock Copolymer PDTCD-PLGA (1) Synthesis and characterization of vinyl-containing poly(lactic acid-glycolic acid) polymer (PLGA-Ac) Under vacuum conditions, 1.48 g of synthesized PLA-Ac and 5.22 g of glycolide (45 mmol) were added to a 100 mL three-necked beaker. Stannous octoate (0.81 mg, 0.002 mmol) was injected via a gas-tight syringe. The mixture was reacted at 120°C for 12 h under argon. After the reaction, the mixture was cooled to room temperature and precipitated with approximately 200 mL of methanol, yielding a large amount of flocculent precipitate. Centrifugation afforded a white precipitate, which was then dried under vacuum at 40°C to obtain the polymer, PLGA-Ac, in a yield of approximately 52%.

[0054] 1 H NMR (400 MHz, Chloroform-d), δ=6.11 (s, 1H), 5.59 (s, 1H), 5.02 (s, 41H), 4.35 (s, 8H), 1.79-1.05 (m, 142H), as Figure 8 .

[0055] (2) Synthesis of amphiphilic block copolymer PDTCD-PLGA 0.50 g of the macromolecular chain transfer agent PDTCD, 0.25 g of the vinyl monomer PLGA-Ac, 0.005 g of the initiator AIBN (0.03 mmol), and 50 mL of DMF were added to a 100 mL three-necked flask. RAFT polymerization was carried out at 70°C under vacuum for 5 h. After the reaction, the yellow reaction solution was cooled to room temperature and precipitated with approximately 200 mL of acetone, resulting in a large amount of flocculent precipitate. Centrifugation afforded a white precipitate, which was then dried in vacuum at 40°C to afford the amphiphilic diblock product PDTCD-PLGA in approximately 64% yield.

[0056] 1 H NMR (400 MHz, DMSO-d6), δ=7.72 (s, 1H), 7.44 (s,2H), 7.14 (s, 1H), 5.74 (s, 91H), 5.26 (d, J=1.0 Hz, 3H), 5.01-4.76 (m,123H), 4.47 (s, 19H), 3.63 (s, 244H), 3.33 (s, 645H), 2.81 (d, J=65.2 Hz, 5036H), 2.08 (d, J = 2.0Hz, 1783H), 1.92 (s, 26H), as Figure 9 .

[0057] (3) Preparation of polymer quantum dots: The concentration is 1×10 -3 A PDTCD-PLGA aqueous solution with a concentration of 100 mg / mL was ultrasonically treated, and the homopolymer aqueous solution was pipetted with a rubber-tipped pipette and dropped onto the ultra-thin carbon film. The solution was heated at a constant temperature (25°C) to completely evaporate the solvent, thereby obtaining polymer quantum dots PDTCD-PLGA QDs.

Claims

1. An amphiphilic diblock copolymer based on a β-cyclodextrin chain transfer agent, characterized in that: The copolymer is formed by using a β-cyclodextrin homopolymer PDTCD containing a dithioester structure as a macromolecular chain transfer agent and initiating polymerization of a hydrophobic medical polymer monomer containing a vinyl group at the end through a RAFT polymerization reaction. The copolymer can self-assemble in water to form polymer quantum dots.

2. The amphiphilic diblock copolymer according to claim 1, characterized in that The hydrophobic medical polymer monomer containing a vinyl group at the end is selected from at least one of the following: Vinyl-modified polyethylene glycol-polycaprolactone PEG-PCL-Ac; Vinyl-modified polylactide-glycolic acid polymer PLA-Ac; Vinyl-modified polylactide-polyglycolide-glycolic acid polymer PLGA-Ac.

3. The amphiphilic diblock copolymer according to claim 1, characterized in that The β-cyclodextrin homopolymer PDTCD containing a dithioester structure is prepared by RAFT polymerization of vinyl monomers derived from β-cyclodextrin.

4. A method for synthesizing the amphiphilic diblock copolymer according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) β-cyclodextrin homopolymer PDTCD containing a dithioester structure, hydrophobic medical polymer monomers PEG-PCL-Ac, PLA-Ac or PLGA-Ac containing a vinyl group at the end, and initiator AIBN were dissolved in N,N-dimethylformamide and subjected to RAFT polymerization reaction at 60-80°C for 4-6 h under vacuum conditions; (2) After the reaction is completed, the mixture is cooled to room temperature, precipitated with acetone, centrifuged, and vacuum dried to obtain copolymers PDTCD-PEG-PCL, PDTCD-PLA, or PDTCD-PLGA; (3) The copolymer is dissolved in water and self-assembled to form polymer quantum dots PDTCD-PEG-PCL QDs, PDTCD-PLA QDs or PDTCD-PLGA QDs.

5. The synthesis method according to claim 4, characterized in that In step (1), the mass ratio of PDTCD to the hydrophobic medical polymer monomer containing a terminal vinyl group is 1:1 to 3:

1.

6. The synthesis method according to claim 4, characterized in that The concentration of the copolymer self-assembly in water in step (3) is ≥1×10 -3 mg / mL.

7. The synthesis method according to claim 4, characterized in that The method for synthesizing the β-cyclodextrin homopolymer containing a dithioester structure comprises the following steps: (1) Synthesis of CD-OTS: Under alkaline conditions, β-cyclodextrin and p-toluenesulfonyl chloride were reacted at 0-5°C for 4-6 h, and the sulfonylated product CD-OTS was obtained after purification; the molar ratio of β-cyclodextrin to p-toluenesulfonyl chloride was 1:0.8-1.0; (2) Synthesis of DTCD: CD-OTS and diethylenetriamine were dissolved in anhydrous N-methylpyrrolidone and reacted at 60-80°C for 7-8 hours under the catalysis of potassium iodide. After precipitation and purification, a linear polyamine short-chain modified β-cyclodextrin derivative DTCD was obtained; the molar ratio of CD-OTS to diethylenetriamine was 1:3-4; (3) Synthesis of DTCD-Ac: Using anhydrous N, N-dimethylformamide as solvent, DTCD and methacrylic acid were esterified by activation with dicyclohexylcarbodiimide and N-hydroxysuccinimide to produce β-cyclodextrin-derived vinyl monomer DTCD-Ac. The esterification reaction was carried out in two stages: first at 0-5°C for 1-2 h, then at room temperature for 35-40 h. The molar ratio of DTCD to methacrylic acid was 1:1-1.

5. (4) Synthesis of homopolymer PDTCD: Using N,N-dimethylformamide as solvent, 4-cyano-4-(thiobenzoylthio)valeric acid as chain transfer agent, and azobisisobutyronitrile as initiator, DTCD-Ac monomer was converted into β-cyclodextrin homopolymer PDTCD containing a dithioester structure through RAFT polymerization reaction. The conditions of RAFT polymerization reaction were: molar ratio of DTCD-Ac to chain transfer agent was 1:0.8~1.2, reaction temperature was 60~80℃, and reaction time was 4~6h.

8. The synthesis method according to claim 4, characterized in that The synthesis method of the hydrophobic medical polymer monomer containing vinyl groups at the end comprises: PEG-PCL-Ac: Polyethylene glycol-polycaprolactone PEG-PCL and methacryloyl chloride are reacted in tetrahydrofuran with triethylamine as a base at room temperature for 20-25 h. The molar ratio of methacryloyl chloride to PEG-PCL is 100:1-50:

1. PLA-Ac: Ring-opening polymerization of lactide and 2-hydroxyethyl methacrylate at 110-130°C for 15-20 hours, catalyzed by stannous octoate; the mass ratio of lactide to 2-hydroxyethyl methacrylate is 20:1-25:

1. PLGA-Ac: PLA-Ac and glycolide are copolymerized under the catalysis of stannous octoate. The reaction is carried out under argon protection at a temperature of 110-130°C for 10-15 hours. The mass ratio of PLA-Ac to glycolide is 1:3-1:

4.

9. A polymer quantum dot, characterized in that The amphiphilic diblock copolymer according to any one of claims 1 to 3 is self-assembled, has a particle size of ≤6 nm, has aggregation-induced emission characteristics, a fluorescence quantum yield of ≥14%, a fluorescence lifetime of ≥225 ns, and has good biocompatibility.

10. Use of the polymer quantum dots according to claim 9 as fluorescent probes in the preparation of bioluminescent imaging agents or tumor monitoring agents.

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