Photo-crosslinkable stabilized temperature-responsive ionic polymer micelles and methods of preparation

Abstract

The application discloses a preparation method of photo-crosslinking stabilized temperature-responsive ionic polymer micelles, and specifically comprises the following steps: preparing a PNIPAM-based polymer and a urea group-containing intermediate; preparing a positive ion polymer by using the urea group-containing product, N-triethyl-(4-vinyl benzyl) ammonium chloride, p-styrene-7-hydroxy-4-methyl coumarin and AIBN; preparing a negative ion polymer by using the urea group-containing product, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methyl coumarin and AIBN; and irradiating aqueous solutions of the positive ion polymer and the negative ion polymer with ultraviolet light, and then mixing to obtain composite ionic polymer micelles. Based on a modular polymerization route of thiol-ene click chemistry, a temperature-sensitive PNIPAM unit, an ultraviolet light-crosslinkable photosensitive group and an ionizable quaternary ammonium salt / sulfonate group are integrated, so that a temperature-ultraviolet light dual-responsive polymer with positive / negative ion characteristics is constructed.

Description

Technical Field

[0001] This invention belongs to the field of functional polymer and smart responsive material preparation technology, specifically relating to a method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles, and also relating to photocrosslinkable and stabilized temperature-responsive ionic polymer micelles and their applications. Background Technology

[0002] With the rapid development of biomedicine, intelligent sensing, drug delivery, and environmentally responsive materials, the development of intelligent polymer materials that possess multiple stimulus responses, structural stability, and tunable functions has become a research hotspot. Among these, temperature-responsive polymers, particularly poly(N-isopropylacrylamide) (PNIPAM), exhibit great potential in drug controlled release, tissue engineering, and smart coatings due to their rapid and reversible volume phase transition behavior near the critical solution temperature (LCST). Meanwhile, photoresponsiveness, due to its high temporal and spatial controllability, is often incorporated into material systems to achieve precise functional regulation. Combining temperature and photoresponsiveness can endow materials with richer stimulus-response logic and more intelligent behavioral regulation capabilities.

[0003] However, existing technologies for such multifunctional stimulus-responsive polymer systems still face numerous challenges. Firstly, in terms of synthesis, precisely integrating temperature-sensitive, photosensitive, and specific functional groups (such as ionic groups) onto the same polymer chain often involves multi-step reactions, harsh reaction conditions, or the use of metal catalysts. This results in complex and inefficient synthetic pathways, potentially affecting the biocompatibility of the material and hindering the achievement of highly designable structures and large-scale production. Secondly, regarding functional integration and performance, existing research largely focuses on single-responsive or simple dual-responsive systems, while the construction and synergistic regulation of polymer micelle systems integrating temperature response, photocrosslinking stabilization, and ionic properties are still insufficient. In particular, while positive and negative ion polymer composite systems formed based on electrostatic interactions can control interfacial properties and assembly structures, near the isoelectric point, excessive electrostatic attraction can easily lead to irreversible sedimentation or phase separation of micelles or aggregates, severely affecting their long-term stability and reliability as functional materials.

[0004] To improve the stability of such ionic complex systems, traditional methods often involve introducing steric hindrance, adjusting the ionic strength of the solution, or adjusting the pH. However, these methods typically struggle to achieve dynamic and reversible control over the micelle structure and properties. Therefore, there is an urgent need to develop a novel strategy that is easy to synthesize, highly integrated with its functions, and capable of precise and active control over the micelle structure and stability under complex conditions, especially in electrostatic interaction environments. Summary of the Invention

[0005] The first objective of this invention is to provide a method for preparing temperature-responsive ionic polymer micelles that can be photocrosslinked and stabilized, wherein the polymer micelles are temperature-responsive and UV-crosslinking responsive.

[0006] A second objective of this invention is to provide a method for preparing temperature-responsive ionic polymer micelles that can be photocrosslinked and stabilized.

[0007] A third objective of this invention is to provide a method for preparing temperature-responsive ionic polymer micelles that can be photocrosslinked and stabilized for use in drug delivery, biosensors, and filtration membranes.

[0008] The technical solution adopted in this invention is a method for preparing temperature-responsive ionic polymer micelles that can be photocrosslinked and stabilized, specifically implemented according to the following steps:

[0009] Step 1: Prepare PNIPAM-based polymers; Step 2: Prepare urea-containing intermediates; Step 3: Prepare the positive ionic polymer PQA using urea-containing products, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN; Step 4: Prepare the negative ion polymer PSA using urea-containing products, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN; Step 5: Irradiate the aqueous solution of positive ion polymer PQA with ultraviolet light, irradiate the aqueous solution of negative ion polymer PSA with ultraviolet light, and then mix the two solutions to obtain composite ionic polymer micelles.

[0010] The invention is further characterized in that, Step 1 specifically involves: Under nitrogen protection, β-mercaptoethylamine, N-isopropylacrylamide, and azobisisobutyronitrile were dissolved in N,N-dimethylformamide solvent at a molar ratio of 2–2.2:100–102:1–1.2. The mixture was stirred at 78–85 °C for 12–24 h. After the reaction was completed, the product was precipitated in ice-cold diethyl ether, filtered, washed 2–3 times with diethyl ether, and dried under vacuum to obtain the polymer.

[0011] Step 2 specifically involves: The polymer was dissolved in anhydrous chloroform and stirred in an ice bath at 0–4 °C until dissolved to obtain a polymer solution. 2-Ethyl isocyanate acrylic acid was dissolved in anhydrous chloroform to obtain a 2-ethyl isocyanate acrylic acid solution. Under light-protected conditions, in an ice bath at 0–4 °C, and with stirring, the 2-ethyl isocyanate acrylic acid solution was slowly added dropwise to the polymer solution over a period of 30–60 min. After the addition was complete, the ice bath was removed, and the reaction was continued to be stirred at 0–4 °C for 4–6 h. After the reaction was complete, the product was rotary evaporated, precipitated with diethyl ether, washed, and dried under vacuum to obtain the urea-containing product.

[0012] In step 3, specifically: the urea-containing product, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN are dissolved in DMF, and a free radical polymerization reaction is carried out at 78-85°C for 12-24 h. After dialyzing and freeze-drying, the positive ionic polymer PQA is obtained. The mass ratio of the urea-containing product, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN is 1.38-2.07:0.08-0.12:0.04-0.06:0.0013-0.0026.

[0013] In step 4, specifically: the urea-containing product, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN are dissolved in DMF, and a free radical polymerization reaction is carried out at 78-85 °C for 12-24 h. After dialyzing and freeze-drying, the negative ion polymer PSA is obtained. The mass ratio of the urea-containing product, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN is 1.39-2.08:0.08-0.12:0.03-0.05:0.0013-0.0026.

[0014] In step 5, the concentration ratio of negative ion polymer PSA to positive ion polymer PQA in the composite ionic polymer micelles is 0.02–1:1. The UV irradiation time of the aqueous solution of positive ion polymer PQA is 2.5–29 min; the UV irradiation time of the aqueous solution of negative ion polymer PSA is 9–50 min.

[0015] The beneficial effects of this invention are: (1) Superior synthesis method: This invention adopts the "thiol-ene" click chemistry strategy, which has mild reaction conditions, high efficiency, no metal catalysts involved, good biocompatibility, and realizes modular and controllable synthesis of functional polymers, which facilitates precise design of polymer structure and site-specific introduction of functional groups; (2) High integration of functions: A polymer system integrating temperature response (through PNIPAM segments), ultraviolet light response (through photosensitive groups that can dimerize on the side chains) and positive / negative ion characteristics (through quaternary ammonium salt and sulfonic acid / sulfonate groups) was successfully prepared, realizing the coupling of multiple stimulus response capabilities; (3) Performance can be precisely controlled: By adjusting the polymer concentration, the mixing ratio of positive and negative ion polymer micelles, and the degree of crosslinking under ultraviolet light, the critical phase transition temperature (LCST), phase transition amplitude (the difference between the top and bottom of transmittance ΔT), Zeta potential, hydrodynamic dimensions, and solution stability of the composite micelle system can be systematically controlled. In particular, light irradiation, as an external triggering method, enables precise spatiotemporal control of the micelle interaction strength and stability.

[0016] (4) High stability: Ultraviolet light crosslinking is used as a "stabilization switch"; Experiments show that moderate photocrosslinking of polymer micelles can effectively "solidify" or "lock" the microstructure of micelles, thereby weakening the excessive electrostatic interaction between positive and negative ion chains that is prone to irreversible precipitation, significantly improving the long-term storage stability of the composite micelle system and its application feasibility in complex environments. Attached Figure Description

[0017] Figure 1 This is a synthetic reaction route diagram of the PNIPAM-based polymer of this invention; Figure 2 This is a synthetic reaction route diagram for the urea-based intermediate of the present invention; Figure 3 This is a schematic diagram of the synthesis reaction of the positive ion polymer PQA of the present invention; Figure 4 This is a synthesis reaction route diagram of the negative ion polymer PSA of the present invention; Figure 5 This is a temperature-transmittance curve of aqueous micelles of PQA, a positive ion polymer at different concentrations. Figure 6 This is a temperature-transmittance curve of PSA micelle aqueous solutions with different negative ion polymers; Figure 7 This is a graph showing the difference between the top and bottom permeability of aqueous solutions of positive and negative ion polymers at different concentrations as a function of concentration. Figure 8a This is a graph showing the change in transmittance of an aqueous solution of the positive ion polymer PQA micelles during five heating and cooling cycles. Figure 8b These are visual diagrams of the aqueous micelle solution of the positive ion polymer PQA at 20℃ and 50℃. Figure 9a This is a graph showing the change in transmittance of an aqueous solution of PSA micelles containing negative ions during five heating and cooling cycles. Figure 9b These are visual diagrams of PSA micelle aqueous solution containing negative ion polymers at 20℃ and 50℃. Figure 10 This is the UV-Vis absorption spectrum of an aqueous solution of the positive ion polymer PQA micelles; Figure 11 This is the UV-Vis absorption spectrum of an aqueous solution of PSA micelles, a negative ion polymer. Figure 12a This is a particle size distribution diagram of the positive ion polymer PQA micelle aqueous solution under different degrees of photocrosslinking; Figure 12b This is a graph showing the changes in DCR values ​​of PQA micelle aqueous solutions with different degrees of photocrosslinking. Figure 12c The graph shows the zeta potential changes of the positive ion polymer PQA micelle aqueous solution under different degrees of photocrosslinking. Figure 13a This is a particle size distribution diagram of PSA micelle aqueous solution with different degrees of photocrosslinking; Figure 13b This is a graph showing the changes in DCR values ​​of PSA micelle aqueous solutions with different degrees of photocrosslinking. Figure 13c The graph shows the zeta potential changes of PSA micelle aqueous solution with different degrees of photocrosslinking. Figure 14a This is a graph showing the changes in transmittance when different proportions of negative ion polymer PSA micelle aqueous solution are added to positive ion polymer PQA micelle aqueous solution. Figure 14b This is a graph showing the changes in DCR values ​​when different proportions of negative ion polymer PSA micelle aqueous solution are added to positive ion polymer PQA micelle aqueous solution. Figure 14c This is a graph showing the change in zeta potential when different proportions of negative ion polymer PSA micelle aqueous solution are added to positive ion polymer PQA micelle aqueous solution. Figure 15a This is a graph showing the change in transmittance during the heating and cooling process when different proportions of negative ion polymer PSA micelle aqueous solution are added to positive ion polymer PQA micelle aqueous solution. Figure 15b This is a graph showing the change in the difference between the top and bottom as a function of the positive and negative ion ratio when different proportions of negative ion polymer PSA micelle aqueous solution are added to positive ion polymer PQA micelle aqueous solution. Figure 16a This is a curve showing the transmittance variation of aqueous solutions of positive and negative ion polymer micelles with different degrees of photocrosslinking, mixed at different concentration ratios. Figure 16bThis is a graph showing the changes in DCR values ​​after aqueous solutions of positive and negative ion polymer micelles with different degrees of photocrosslinking are mixed at different concentration ratios. Figure 16c This is a graph showing the change in Zeta potential after aqueous solutions of positive and negative ion polymer micelles with different degrees of photocrosslinking are mixed in different concentration ratios. Figure 16d This is a visual representation of aqueous solutions of positive and negative ion polymer micelles with different degrees of photocrosslinking, mixed at different concentration ratios and left to stand for 4 hours. Figure 17a The UV-Vis absorption spectra are those of two positive and negative ion polymer micelle solutions with different degrees of crosslinking, mixed at a concentration ratio of 1:1. Figure 17b This is a temperature-sensitive curve of a composite system after mixing two positive and negative ion polymer micelle solutions before and after deep cross-linking, based on a heating-cooling cycle test. Detailed Implementation

[0018] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0019] This invention relates to a method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles based on the mercapto-olefin click reaction, which is specifically implemented according to the following steps: Step 1, preparing PNIPAM-based polymers, specifically: Under nitrogen protection, β-mercaptoethylamine, N-isopropylacrylamide (NIPAM), and the free radical initiator azobisisobutyronitrile (AIBN) were dissolved in N,N-dimethylformamide (DMF) solvent (40 mL–50 mL) at a molar ratio of 2–2.2:100–102:1–1.2. The mixture was stirred at 78–85 °C for 12–24 h. After the reaction was completed, the mixture was poured into excess ice-cold diethyl ether to precipitate, filtered, washed 2–3 times with diethyl ether, and dried under vacuum to obtain a white solid polymer. Step 2, prepare the urea-containing intermediate, specifically as follows: The polymer was dissolved in anhydrous chloroform and magnetically stirred under ice bath conditions at 0–4°C until completely dissolved to obtain a polymer solution; the mass-to-volume ratio of polymer to anhydrous chloroform was 2.00 g–2.20 g : 20 mL–22 mL. 2-Ethyl isocyanate acrylic acid was dissolved in anhydrous chloroform to obtain a 2-ethyl isocyanate acrylic acid solution; the mass-to-volume ratio of 2-ethyl isocyanate acrylic acid to anhydrous chloroform was 0.06 g to 0.09 g: 2 mL to 3 mL. Under conditions of light protection, ice bath at 0–4 °C, and continuous stirring, a solution of 2-isocyanate ethyl acrylic acid was slowly added dropwise to the polymer solution over a period of 30–60 min. After the addition was complete, the ice bath was removed, and the reaction was continued to be stirred at 0–4 °C for 4–6 h. After the reaction was completed, most of the solvent was removed by rotary evaporation, and the residue was precipitated with diethyl ether, washed, and vacuum dried to finally obtain a white solid urea-containing product. Step 3, prepare the positive ionic polymer PQA, specifically as follows: Urea-containing products, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and initiator AIBN were dissolved in DMF and subjected to free radical polymerization at 78–85 °C for 12–24 h. The reaction solution was dialyzed (MWCO 3500) to remove small molecule impurities, and then freeze-dried to obtain the target positive ionic polymer PQA. The mass ratio of urea-containing product, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN is 1.38–2.07: 0.08–0.12: 0.04–0.06: 0.0013–0.0026. Step 4, prepare the negative ion polymer PSA, specifically as follows: The urea-containing product, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and initiator AIBN were dissolved in 10–15 mL of DMF and subjected to free radical polymerization at 78–85 °C for 12–24 h. The reaction solution was dialyzed (MWCO3500) to remove small molecule impurities, and then freeze-dried to obtain the target anionic polymer PSA.

[0020] The mass ratio of urea-containing product, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN is 1.39–2.08: 0.08–0.12: 0.03–0.05: 0.0013–0.0026. Step 5: Irradiate the aqueous solution of the positive ion polymer PQA with ultraviolet light for 2.5–29 min; irradiate the aqueous solution of the negative ion polymer PSA with ultraviolet light for 9–50 min; then mix the two solutions to obtain composite ionic polymer micelles. The concentration ratio of the negative ion polymer PSA to the positive ion polymer PQA in the composite micelle solution is 0.02:1 to 1:1.

[0021] The method of this invention aims to solve the problems of cumbersome synthesis, low functional integration, and poor stability of existing multifunctional stimulus-responsive polymer systems. Based on the modular polymerization route of "thiol-ene" click chemistry, the thermosensitive poly(N-isopropylacrylamide) (PNIPAM) motif, the UV-crosslinkable photosensitive group (coumarin derivative), and the ionizable quaternary ammonium salt / sulfonate group are integrated to construct a temperature-UV dual-responsive polymer with both positive and negative ion properties, and the corresponding polymer micelle system is constructed based on this. Thermosensitive principle: Its core driving force originates from the conformational change of PNIPAM in the polymer chain segments. PNIPAM segments, through hydrogen bonds between amide and isopropyl groups and their own hydrophobic interactions, exhibit an extended hydrophilic conformation below their lowest critical dissolution temperature (LCST), dissolving in water and producing a clear solution. When the temperature rises above the LCST, the hydrogen bonds are broken, hydrophobic interactions intensify, the molecular chains collapse and aggregate, forming insoluble micelles or precipitates, leading to increased turbidity in the solution, exhibiting LCST-type phase behavior.

[0022] Photoresponse principle: A coumarin derivative (p-styrene-7-hydroxy-4-methylcoumarin) is introduced as a photosensitive group into the polymer side chain. Under ultraviolet light irradiation at a specific wavelength (e.g., 365 nm), a [2+2] cycloaddition reaction can occur between the coumarin structural units, thereby forming covalent cross-links between polymer chains. This cross-linking structure can lock the internal microstructure of the micelles, changing their hydrodynamic dimensions, surface charge (Zeta potential), and internal density. More importantly, this cross-linking structure can effectively restrict the movement of polymer chain segments, weakening excessive micelle aggregation and irreversible precipitation that may be caused by temperature changes or interactions between positive and negative ions.

[0023] The principle of synergistic stimulation and stability enhancement: This invention creatively uses photocrosslinking as a "stabilization switch" to regulate electrostatic interactions. In a mixed system of positive ion polymers (PQA) and negative ion polymers (PSA), electrostatic interactions are the core driving force for the formation of composite micelles, but excessively strong electrostatic interactions can also easily lead to the system approaching its isoelectric point (C). PSA / C PQAIrreversible precipitation occurs when the concentration of ions is approximately 0.75. By irradiating the micelles with ultraviolet light to form a cross-linked network, the micelle structure can be physically solidified, significantly weakening the dynamic and excessively strong electrostatic attraction / repulsion between positive and negative ion chains, thus acting as a "shield" or "buffer." Experiments show that, compared to the uncross-linked system, the composite micelle system with deep ultraviolet cross-linking (e.g., PD = 80%) exhibits a flatter curve of zeta potential versus mixing ratio, higher solution clarity, and significantly reduced precipitation after standing. This demonstrates that photocross-linking, as an external triggering mechanism, can synergistically work with thermosensitive behavior and ion interactions to achieve synergistic control and regulation of the phase behavior, size, charge, and long-term stability of the composite micelle system. The ionic polymer micelles of this invention, possessing dual-response characteristics, have broad application prospects in several cutting-edge fields, as detailed below: In the field of drug delivery, this material can be used to construct a dual-gated intelligent drug delivery system. Drug molecules can be encapsulated in a hydrophobic micelle core, and initial release can be achieved by triggering changes in the micelle structure at body temperature (close to or above LCST). Furthermore, the release rate can be precisely controlled through an "on-off" mechanism or the release behavior can be "locked in" by localized ultraviolet light irradiation. Its ionic properties allow it to interact with biomolecules with opposite charges (such as proteins and nucleic acids), making it suitable for the co-delivery of gene drugs or protein drugs. The "stabilization switch" introduced by photocrosslinking effectively prevents the carrier from prematurely disintegrating and releasing drugs due to the complex electrostatic environment in the bloodstream, significantly improving delivery efficiency and the precision of tumor-targeted therapy.

[0024] In the field of biosensing and diagnostics, high-sensitivity biosensors can be developed by utilizing their temperature- and light-adjustable phase transition behavior and photocrosslinking ability to "lock" size / charge. These sensors can be used to detect temperature, specific ions, or biomarkers, and their stable signal output characteristics can improve the reproducibility and accuracy of detection.

[0025] In the field of environmentally responsive coatings and separation membranes, this material can be used to prepare smart filter membranes or coatings. Its permeability and selectivity can be controlled by temperature or light, and it can be used for water treatment, material separation or controlled adsorption / desorption processes. The structural stability brought about by photocrosslinking can extend the service life of the material under complex working conditions.

[0026] Example 1 The present invention discloses a method for preparing ionic polymer micelles with dual-response characteristics, which is specifically implemented according to the following steps: Step 1, Preparation of PNIPAM-based polymers, such as Figure 1 As shown, the specific steps are as follows: Under nitrogen protection, β-mercaptoethylamine (0.14 g), N-isopropylacrylamide (NIPAM) (10.00 g), and the free radical initiator azobisisobutyronitrile (AIBN) (0.14 g) were dissolved in N,N-dimethylformamide (DMF) solvent (40 mL) at a molar ratio of 2:100:1, and the mixture was stirred at 80 °C for 18 h. After the reaction was completed, the mixture was poured into excess ice-cold diethyl ether to precipitate, filtered, washed three times with diethyl ether, and dried under vacuum to obtain the polymer (white solid, 7.08 g), with a yield of 69.82%.

[0027] Step 2, synthesis of urea-containing intermediates, such as Figure 2 As shown, specifically: 2.00 g of polymer A was dissolved in 20 mL of anhydrous chloroform in a round-bottom flask and magnetically stirred at 0°C under ice bath conditions until completely dissolved. 0.06 g of 2-ethyl isocyanate acrylic acid was dissolved in 2 mL of anhydrous chloroform and placed in a constant-pressure dropping funnel. Under light-protected conditions, at 0°C under ice bath conditions, and with continuous stirring, the solution in the constant-pressure dropping funnel was slowly added dropwise to the polymer solution in the round-bottom flask over a period of 45 min. After the addition was complete, the ice bath was removed, and the reaction was continued at 0°C with stirring for 4 h. After the reaction was complete, most of the solvent was removed by rotary evaporation. The residue was precipitated with diethyl ether, washed, and dried under vacuum to obtain a white solid containing urea, with a mass of 1.88 g and a yield of 91.26%.

[0028] Step 3, synthesis of the positive ion polymer PQA, such as... Figure 3 As shown, specifically: Urea-containing product (1.38 g), N-triethyl-(4-vinylbenzyl)ammonium chloride (0.08 g), p-styrene-7-hydroxy-4-methylcoumarin (0.04 g), and initiator AIBN (0.0026 g) were dissolved together in 10 mL of DMF at a molar ratio of 10:10:4:1, and a free radical polymerization reaction was carried out at 80 °C for 18 h. The reaction solution was dialyzed (MWCO 3500) to remove small molecule impurities, and then freeze-dried to obtain the target positive ionic polymer PQA.

[0029] Step 4, synthesis of the negative ion polymer PSA, such as Figure 4 As shown, specifically: Urea-containing product (1.39 g), sodium p-styrenesulfonate (0.08 g), p-styrene-7-hydroxy-4-methylcoumarin (0.03 g), and initiator AIBN (0.0026 g) were dissolved together in 10 mL of DMF at a molar ratio of 10:10:4:1, and a free radical polymerization reaction was carried out at 80 °C for 18 h. The reaction solution was dialyzed (MWCO 3500) to remove small molecule impurities, and then freeze-dried to obtain the target anionic polymer PSA.

[0030] Step 5, Preparation of aqueous solutions of positive and negative ion polymer micelles: Two homogeneous and stable aqueous solutions of polymer micelles were prepared by direct dissolution method. The specific steps are as follows: 100 mg of positive and negative ion polymer powder were weighed and dissolved in 10 mL of deionized water to prepare a stock solution with a concentration of 10.0 mg / mL. The solution was magnetically stirred at room temperature until it was evenly dispersed, and then diluted sequentially to obtain micelle aqueous solutions with concentrations of 8.0, 5.0, 2.0, 1.5, 1.0, 0.75, 0.5, and 0.25 mg / mL. Example 2 Study on Dual-Responsive and Ion-Interaction Systems This embodiment systematically studies the thermosensitive properties, ion interactions, and photocrosslinking regulation effects of the two polymer micelle aqueous solutions prepared in Example 1.

[0031] Basic temperature sensitivity test: Take 1.5 mL of micelle aqueous solution samples of PQA and PSA at various concentrations (10.0, 8.0, 5.0, 2.0, 1.5, 1.0, 0.75, 0.5, 0.25 mg / mL) and place them in a quartz cuvette. Using a UV-6100 double-beam UV-Vis spectrophotometer, measure the transmittance (T%) of the solution at a specific wavelength (e.g., 880 nm) in the temperature range of 20–50 °C at 2 °C intervals.

[0032] like Figure 5The figure shows the temperature-transmittance curves of nine groups of aqueous solutions of the positively charged polymer PQA micelles with different concentrations (solid lines represent transmittance changes during heating; dashed lines represent transmittance changes during cooling). As can be seen from the figure, the temperature-sensitive characteristic curves of the nine groups of aqueous solutions of the positively charged polymer PQA micelles with different concentrations all exhibit good reversible recovery; and the LCST of each solution is around 32℃. This is because the LCST of PNIPAM in the polymer chain is 32℃ (PNIPAM segments form hydrogen bonds with water molecules at low temperatures, existing in a hydrated state, resulting in good light transmittance; at high temperatures, the hydrogen bonds break, PNIPAM segments hydrophobically aggregate, and the light transmittance of the solution decreases). At 20℃, the permeability of the solutions was consistently above 97.26%, but at 50℃, the permeability increased significantly with decreasing concentration (at 50℃, the permeability of a 10 mg / mL PQA solution was 0.33%, while the permeability of a 0.25 mg / mL PQA solution was 82.54%). This phenomenon also significantly affected the phase transition amplitude (the difference between the peak and trough of permeability, ΔT), such as... Figure 7 As shown, when the concentration of the positive ion polymer PQA micelle solution increased from 0.25 mg / mL to 5.0 mg / mL, ΔT increased exponentially from 15.83% to 95.37%. Subsequently, when the concentration increased to 10.0 mg / mL, ΔT slowly increased to 96.92%.

[0033] like Figure 6 The figure shows the temperature-transmittance curves of nine groups of PSA micelle aqueous solutions with different concentrations of negative ion polymers (solid lines represent transmittance changes during heating; dashed lines represent transmittance changes during cooling). The figure shows that the temperature-sensitive characteristic curves of the nine groups of PSA micelle aqueous solutions with different concentrations of negative ion polymers all exhibit good reversible recovery; and the LCST of each solution is around 32℃ (the principle is the same as PQA, with the PNIPAM segment's temperature sensitivity dominating the phase transition); at 20℃, the transmittance of the solution continuously increases from 11.21% to 95.03% as the concentration decreases from 10.0 mg / mL to 0.25 mg / mL; at 50℃, the transmittance of the solution continuously increases from 53.61% to 87.56% as the concentration decreases from 10.0 mg / mL to 0.25 mg / mL; this phenomenon also significantly affects the phase transition amplitude (the difference between the peak and trough of transmittance, ΔT), as shown in the figure. Figure 7 As shown, when the concentration of the negative ion polymer PSA micelle solution increased from 0.25 mg / mL to 2.0 mg / mL, ΔT increased exponentially from 7.47% to 37.21%. Subsequently, when the concentration increased to 10.0 mg / mL, ΔT slowly decreased to 11.21%.

[0034] Example 3 Furthermore, 1.5 mL of micelle aqueous solutions of 2.0 mg / mL PQA and PSA were placed in quartz cuvettes, respectively. Using a UV-6100 double-beam UV-Vis spectrophotometer, the transmittance (T%) of the solution at a specific wavelength (e.g., 880 nm) was measured at 20 ℃ and 50 ℃. Five heating and cooling cycles were performed to verify its temperature-sensitive reversible characteristics. Visual images of the cuvettes at 20 ℃ and 50 ℃ were obtained.

[0035] like Figure 8a The figure shows the transmittance changes of a 2 mg / mL positive ion polymer PQA micelle aqueous solution during five heating and cooling cycles. As can be seen from the figure, at low temperatures, the transmittance of the solution remained above 99% (nearly completely transparent), while at high temperatures, the transmittance was between 21% and 26% (the solution appeared white and turbid). This indicates that the positive ion polymer PQA micelle aqueous solution has excellent temperature-sensitive and reversible properties. This is because at low temperatures, the PNIPAM segments in the polymer chain form hydrogen bonds with water molecules and are dispersed in the solution in a hydrated state, resulting in excellent light transmittance. At high temperatures, the hydrogen bonds break, the PNIPAM segments hydrophobically aggregate, forming micelle aggregates, and the light transmittance of the solution decreases significantly. Figure 8b This is a visual representation of the aqueous solution of 2 mg / mL positive ion polymer PQA micelles at 20℃ and 50℃. As can be seen from the figure, the solution is transparent at low temperature and white and turbid at high temperature, and the recovery is good after temperature cycling.

[0036] like Figure 9a The figure shows the transmittance changes of a 2 mg / mL PSA micelle aqueous solution during five temperature cycles. As can be seen from the figure, at low temperatures, the transmittance of the solution remained between 63% and 64% (the solution was lightly transparent), while at high temperatures, the transmittance was between 24% and 27% (the solution was white and turbid). This indicates that the PSA micelle aqueous solution has good temperature-sensitive and reversible properties. This is because at low temperatures, the PNIPAM segments in the polymer chain form hydrogen bonds with water molecules and are dispersed in the solution in a hydrated state (but due to the charge interaction of PSA, the transmittance is weaker than that of PQA at low concentrations); at high temperatures, the hydrogen bonds break, the PNIPAM segments hydrophobically aggregate, forming micelle aggregates, and the transmittance of the solution decreases significantly. Figure 9b This is a visual representation of the aqueous solution of 2 mg / mL negative ion polymer PSA micelles at 20 ℃ and 50 ℃. As can be seen from the figure, the solution is lightly transparent at low temperature and white and turbid at high temperature, and the recovery is good after temperature cycling.

[0037] Example 4 The core regulatory role of photocrosslinking: 365 nm ultraviolet light source: high-intensity point light source (ROLENCE-100UV, 80 mW / cm²) 2).

[0038] Prepare 0.6 mg / mL PQA micelle aqueous solution and 0.4 mg / mL PSA micelle aqueous solution respectively. Take 1.5 mL of each test sample and measure the UV-Vis absorption spectra (230-600 nm) of the two aqueous solutions at 25 °C under different cumulative irradiation times.

[0039] like Figure 10 and 11 The figures show the UV-Vis absorption spectra of 0.6 mg / mL positive ion polymer PQA micelle aqueous solution and 0.4 mg / mL negative ion polymer PSA micelle aqueous solution under 365 nm UV irradiation. A characteristic absorption peak resembling a shoulder appears in the wavelength range of 250–450 nm; the intensity of this characteristic absorption peak decreases significantly with the cumulative duration of 365 nm UV irradiation. This is due to the [2+2] cycloaddition reaction of the coumarin moiety in the polymer. Applying UV irradiation to the 0.6 mg / mL positive ion polymer PQA micelle aqueous solution for a cumulative 2900 s almost reaches the maximum crosslinking degree (i.e., PD value 100%); applying UV irradiation to the 0.4 mg / mL negative ion polymer PSA micelle aqueous solution for a cumulative 7600 s almost reaches the maximum crosslinking degree (i.e., PD value 100%).

[0040] A 4 mg / mL PQA micelle aqueous solution was prepared and subjected to ultraviolet light irradiation for different cumulative durations to achieve crosslinking degrees (PD values) of 10%, 20%, 40%, 60%, and 80%, respectively. The dynamic light scattering particle size distribution, DCR value, and Zeta potential changes of the PQA micelle aqueous solutions with different crosslinking degrees were then measured, as shown in Table 1. The same method was used to measure the dynamic light scattering particle size distribution, DCR value, and Zeta potential changes of the PSA micelle aqueous solutions with different crosslinking degrees (PD = 10%, 20%, 40%, 60%, and 80%).

[0041] Table 1. Crosslinking degree (PD) values ​​of PQA micelle aqueous solution and PSA micelle aqueous solution

[0042] The dynamic light scattering results of 4 mg / mL positive ionic polymer PQA micelle aqueous solution under different degrees of photocrosslinking are as follows: Figure 12aAs shown in the particle size distribution diagram, the peak particle size of the PQA micelles is around 295.3 nm. With the increase of photocrosslinking degree, the peak particle size fluctuates in the range of 255.0~342.0 nm, without showing a monotonically increasing or decreasing trend. This phenomenon indicates that for micelles formed by the single positive ion polymer PQA, photocrosslinking mainly acts on the coumarin moieties inside the micelles, forming intramolecular or covalent crosslinks in the micelle core. Moderate crosslinking may cause a slight shrinkage of the micelle structure (size reduction), while excessive crosslinking may lead to increased segment rigidity or micro-region structural reorganization, causing slight fluctuations in micelle size. However, overall, crosslinking did not cause significant aggregation or disintegration of the PQA single-component micelles, indicating that the crosslinking structure mainly affects the internal stability of the micelles, rather than drastic changes in macroscopic morphology.

[0043] like Figure 12b As shown, with increasing photocrosslinking, the dynamic light scattering (DCR) value (count rate) gradually decreased from 87.40 ± 2.66 kcps to 60.90 ± 3.01 kcps. The DCR value is related to the concentration, size, and refractive index of scattering particles per unit volume. Photocrosslinking "solidifies" the internal structure and shape of the micelles, restricts the movement and conformational relaxation of polymer chains, and reduces the micelles' responsiveness to external perturbations. This may lead to fine-tuning of their refractive index matching or restricted movement, resulting in a systematic weakening of scattering intensity. Furthermore, crosslinking may also slightly reduce the swelling degree of the micelles, causing a decrease in scattering intensity.

[0044] like Figure 12c As shown, the Zeta potential fluctuated between +19.87±1.50 mV and +21.87±1.42 mV, with insignificant changes. This is because the photocrosslinking reaction (the [2+2] cycloaddition of coumarin) mainly occurs within the micelles or on the polymer side chains, and does not change the charge properties and density of the quaternary ammonium salt cationic groups on the polymer chains. Therefore, the charge density and potential on the micelle surface remain essentially unchanged, as expected.

[0045] like Figure 13a As shown, unlike PQA, the peak particle size of PSA micelles decreased from 1718.0 nm to 1106.0 nm. This indicates that PSA may form large aggregates or loose particle structures when uncrosslinked. Photocrosslinking enables covalent connections between PSA segments (especially near the negatively charged sulfonate groups) through coumarin moieties, effectively enhancing the crosslinking density of the polymer network. This "compresses" the originally loose or easily swollen micelle structure, significantly reducing the particle size and resulting in a more compact and stable structure.

[0046] like Figure 13bAs shown, the DCR value gradually decreased from 2972.80±52.82 kcps to 2393.67±37.95 kcps. Considering the significant reduction in particle size, the decrease in DCR value may stem from a combination of two effects: firstly, the reduction in micelle size directly affects the scattering intensity; secondly, similar to PQA, the restricted chain segment movement and internal densification after structural solidification may also reduce the polarizability or dynamic fluctuations of the scatterer. The variation in DCR value of PSA far exceeds that of PQA, which is consistent with its significant reduction in particle size.

[0047] like Figure 13c As shown, the Zeta potential fluctuated between -34.47±0.23 mV and -29.17±1.59 mV, with the change remaining insignificant. Similarly, the photocrosslinking reaction did not change the charge of the sulfonate anionic groups, so the negative charge density and potential on the PSA micelle surface remained essentially stable.

[0048] Example 5 Mixing behavior of positive and negative ions and determination of isoelectric point: The concentration of PQA aqueous solution was fixed at 2 mg / mL, and PSA aqueous solution was gradually added to make the concentration ratio of negative ion polymer PSA to positive ion polymer PQA in the solution reach 0:1, 0.02:1, 0.05:1, 0.10:1, 0.16:1, 0.25:1, 0.36:1, 0.50:1, 0.75:1, 0.86:1 and 1.00:1, respectively. The transmittance (T%), dynamic light scattering DCR value and zeta potential change of the mixed system were measured.

[0049] Test results showed that with the continuous addition of the negative ion polymer PSA micelle aqueous solution, the permeability of the composite micelle solution increased from 99.00% (C PSA / C PQA = 0:1) decreased exponentially to 7.039% (C PSA / C PQA = 0.75), and then the change tended to level off (C PSA / C PQA = 1:1, T% = 7.48% Figure 14a The DCR value increased exponentially from 37.63±1.83 kcps to 3441.30±149.09 kcps. Figure 14b The zeta potential changes from positive to negative. Figure 14c ), in C PSA / C PQA At approximately 0.75, the Zeta potential is 0.039 mV (close to 0 mV), reaching the isoelectric point. These results collectively confirm the formation of complex micelles based on electrostatic interactions.

[0050] The decrease in transmittance is due to the electrostatic attraction between the positively charged polymer PQA micelles and the added negatively charged polymer PSA micelles, which bring them closer together to form larger and denser composite micelles or aggregates. This significantly enhances light scattering and absorption, leading to a sharp increase in solution turbidity. At C PSA / C PQA At approximately 0.75, the positive and negative charges are essentially neutralized in equal amounts, resulting in the strongest electrostatic interaction. This leads to the formation of the largest and most unstable aggregates, with the greatest tendency for precipitation, thus the transmittance reaches its lowest point. The sharp increase in DCR value corresponds to the increase in turbidity, which is direct evidence of the increase in the size and number of complex micelles (or due to aggregation). The change in zeta potential towards zero is a typical manifestation of the electrostatic neutralization process. With the addition of PSA, the positive charge of PQA is gradually neutralized, and the absolute value of the micelle surface potential decreases, eventually approaching zero when CPSA / CPQA ≈ 0.75. At this point, the electrostatic repulsion between micelles is the weakest, and irreversible aggregation and precipitation are most likely to occur.

[0051] Effect of mixing ratio on temperature-sensitive curves: With a fixed PQA aqueous solution concentration of 2 mg / mL, PSA aqueous solution was gradually added to achieve a concentration ratio of 0:1, 0.02:1, 0.05:1, 0.10:1, 0.16:1, 0.25:1, 0.36:1, 0.50:1, 0.75:1, 0.86:1, and 1.00:1, respectively. Within a temperature range of 20–50 °C, the transmittance (T%) of the solution at a specific wavelength (e.g., 880 nm) was measured at 2 °C intervals to investigate the effect of different C... PSA / C PQA The temperature-sensitive curves of the composite system at different ratios were plotted. Based on the test results, the difference in transmittance (ΔT) as a function of temperature during heating and cooling was also plotted. PSA / C PQA Scale change curve.

[0052] like Figure 15a and Figure 15b As shown, the test results revealed that with the continuous addition of the negative ion polymer PSA micelle aqueous solution, the temperature-sensitive characteristic curve of the composite micelle solution changed significantly: (1) at 20 ℃, the initial transmittance of the composite micelle solution gradually decreased with the continuous addition of the negative ion polymer PSA micelle aqueous solution; (2) at 50 ℃, the transmittance of the composite micelle solution slowly decreased with the continuous addition of the negative ion polymer PSA micelle aqueous solution; (3) at different C PSA / C PQA Under the specified conditions, the LCST of the solution fluctuates between 30 and 32 °C; (4) Before the isoelectric point, C PSA / C PQAAs the ratio increases from 0:1 to 0.50:1, the recoverability of the cooling curve (dashed line) gradually deteriorates. When cooling from 50℃ to 20℃, the transmittance of the composite micelle solution fails to recover to the pre-test transmittance value, corresponding to a larger difference in the peak and trough values ​​ΔT between the heating and cooling processes. After the isoelectric point, C... PSA / C PQA As the ratio increased from 0.75:1 to 1.00:1, the recoverability of the cooling curve (dashed line) gradually improved. From 50℃ to 20℃, the transmittance of the composite micelle solution gradually recovered to the value before the test, and the difference between the top and bottom values ​​ΔT during the heating and cooling processes decreased. This indicates that strong electrostatic interactions may have affected the reversibility of the micelles' thermal response.

[0053] The possible reasons for the above changes are: (1) and (2) are observations showing that electrostatic interactions cause significant changes in the size of the composite micelles. In phenomenon (3), the slight fluctuation in LCST indicates that the strong electrostatic interaction between positive and negative ions alters the hydration environment and interaction energy around the PNIPAM chain segments, thereby fine-tuning its hydrophilic-hydrophobic balance and phase transition temperature. In phenomenon (4), before approaching the isoelectric point (C PSA / C PQA (≈0.75), where the electrostatic attraction between positive and negative ions is strongest, forming very dense composite micelles. Upon heating, PNIPAM segments collapse, exacerbating hydrophobic aggregation and segment entanglement within the composite micelles. This strong aggregate structure, driven by both electrostatic and hydrophobic interactions, is too dense, making it difficult for PNIPAM segments to fully rehydrate and expand upon cooling. Consequently, the micelle structure cannot fully recover, resulting in poor transmittance recovery and severe hysteresis. However, above the isoelectric point, excess PSA provides net negative charge to the composite micelles, reintroducing electrostatic repulsion between micelles, which facilitates dispersion after cooling, thus improving reversibility. This indicates that the strength of electrostatic interactions is one of the key factors controlling the reversibility of micelle thermal response.

[0054] Example 6 The effect of light irradiation on the stability of composite micelle systems; Two micelle aqueous solutions with the highest and lowest photocrosslinking degree (PD value) prepared in Example 4 were taken and mixed at different concentration ratios (PQA aqueous solution concentration was fixed at 2 mg / mL). The transmittance (T%), dynamic light scattering DCR value, and Zeta potential change of the composite micelle solution at 25 °C were measured. The changes in PD value before crosslinking were observed and recorded after standing for 4 h. PQA +PD PSA = 0% + 0% (left) and after deep cross-linking (PD) PQA + PD PSA Visual image of a composite micelle solution (79.98% + 73.90%).

[0055] Test results showed that before crosslinking (PD) PQA + PD PSA = 0% + 0%) and after deep cross-linking (PD) PQA + PD PSA When PQA and PSA (79.98% + 73.90%) were mixed at different concentration ratios, the transmittance of both showed an exponential decrease. However, the transmittance of the composite micelle system with deep crosslinking was more gradual than that without crosslinking. Figure 16a After deep crosslinking, the DCR value increased exponentially from 321.90±2.87 kcps to 3687.20±137.20 kcps, with the overall trend consistent with that before crosslinking, but the rate of change was relatively slower. Figure 16b The Zeta potential changes from positive to negative at C. PSA / C PQA When ≈ 0.75, the isoelectric point is reached ( Figure 16c After deep cross-linking, the decrease in Zeta before the isoelectric point is more and slower than the change before cross-linking, and the same is true after the isoelectric point.

[0056] This is because, after deep cross-linking, the photocross-linking effect weakens the strong electrostatic attraction / repulsion between positive and negative ions, acting as a "shield" or "buffer." Ultraviolet light initiates the [2+2] cycloaddition reaction of coumarin units, forming covalent cross-linked networks within the micelles of PQA and PSA. When these pre-cross-linked and cured micelles are mixed again, the mobility of polymer segments (especially charged groups) is significantly restricted by the cross-linking network. Therefore, although electrostatic attraction still exists, charged segments cannot migrate freely, approach closely, and form extremely dense and unstable composites as they do in the uncross-linked form. The cross-linking network, as a physical barrier, limits the effective spatial range and intensity of electrostatic interaction, making the composite micelle structure more "rigid" and "stable," and the aggregation behavior more mild and controllable. This is reflected in the flatter curves of transmittance, DCR, and Zeta potential as a function of mixing ratio, indicating that the degree of aggregation and kinetic processes are suppressed.

[0057] After the two mixed systems were allowed to stand for 4 hours, the crosslinking was observed. (PD) PQA + PD PSA The composite micelle solution (= 0% + 0%) produced a large amount of precipitation, while the deeply cross-linked (PD) solution produced a large amount of precipitation. PQA + PD PSA The precipitation in the composite micelle solution (79.98% + 73.90%) was significantly reduced, and the solution system maintained good stability. Figure 16dThis directly proves that ultraviolet light crosslinking can effectively "lock" the micelle structure, prevent excessive aggregation and precipitation of micelles caused by strong and dynamic electrostatic interactions, and significantly improve the solution stability of the composite system.

[0058] Two micelle aqueous solutions with different degrees of photocrosslinking prepared in Example 4 were taken and mixed at a concentration ratio of 1:1. The UV-Vis absorption spectra of the composite micelle solutions at 25 °C were measured (PQA aqueous solution concentration was 0.2 mg / mL, PSA aqueous solution concentration was 0.15 mg / mL). Samples before crosslinking (PD) were taken. PQA + PD PSA = 0% + 0%) and after deep cross-linking (PD) PQA + PD PSA A 1.5 mL sample of a composite micelle solution (79.98% + 73.90%) was placed in a quartz cuvette (PQA aqueous solution concentration of 2 mg / mL, PSA aqueous solution concentration of 2 mg / mL). Using a UV-6100 double-beam UV-Vis spectrophotometer, the transmittance (T%) of the solution at a specific wavelength (e.g., 880 nm) was measured in the temperature range of 20–50 °C at 2 °C intervals.

[0059] Test results showed that before crosslinking (PD) PQA + PD PSA Two positive and negative ion polymer micelle solutions (0% + 0%) were mixed at a concentration ratio of 1:1. The absorbance at 320 nm in the UV-Vis absorption spectrum was 0.51. As the degree of crosslinking increased, the absorbance at 320 nm in the UV-Vis absorption spectrum decreased continuously. When deep crosslinking (PD) was reached... PQA +PD PSA When (79.98% + 73.90%), the absorbance at 320 nm is 0.14 ( Figure 17a ).

[0060] like Figure 17b As shown, this is the result before crosslinking (PD) PQA + PD PSA = 0% + 0%) and after deep cross-linking (PD) PQA + PD PSAThe results of a temperature cycling test were conducted on a composite system consisting of two positive and negative ion polymer micelle solutions (79.98% + 73.90%) mixed at a concentration ratio of 1:1 (solid line represents the heating process, dashed line represents the cooling process). The figure shows that the initial transmittance of the composite system before crosslinking was 12.49%, while the initial transmittance after deep crosslinking was 19.08%. This comparison indicates that deep crosslinking, followed by mixing two polymer micelle solutions with different charges, effectively improves the initial transmittance of the composite system. After deep crosslinking, the coumarin groups undergo a [2+2] cycloaddition reaction, and the photocrosslinking weakens the strong electrostatic attraction / repulsion between positive and negative ions, acting as a "shield" or "buffer," making the system more stable and less prone to forming insoluble large particles. Furthermore, the cooling curve (dashed line) and the heating curve (solid line) do not completely overlap, indicating a thermal hysteresis effect in the phase transition process of the composite micelle system, which is more pronounced after crosslinking. This lag may be related to the increased energy barrier created by the cross-linked network for the rehydration and stretching of PNIPAM segments during cooling. Additionally, it was noted that before cross-linking (PD... PQA + PD PSA = 0% + 0%) The LCST of the composite system is 28℃, and after deep cross-linking (PD) PQA + PD PSA The LCST of the composite system (79.98% + 73.90%) was 30℃, which is lower than the LCST of the single micelle (32℃). This is likely due to a significant change in the local microenvironment of the PNIPAM segments within the composite micelles. The composite micelles formed by the positive and negative ion polymers exhibit enhanced hydrophobicity (due to electrostatic complex formation) and reduced polarity. Simultaneously, the strong electrostatic interaction exerts a "tightening" effect on the PNIPAM segments, allowing hydrophobic interactions to dominate at lower temperatures, thus inducing a phase transition and shifting the LCST to a lower temperature. The cross-linked micelle structure is more compact, potentially exacerbating this "hydrophobic microenvironment" effect. However, the cross-linking network's restriction on segment movement also has the opposite effect. Under the combined influence, the LCST slightly recovers compared to before cross-linking, but remains lower than that of the single component.

Claims

1. A method for preparing temperature-responsive ionic polymer micelles that can be photocrosslinked and stabilized, characterized in that, The specific steps are as follows: Step 1: Prepare PNIPAM-based polymers; Step 2: Prepare urea-containing intermediates; Step 3: Prepare the positive ionic polymer PQA using urea-containing products, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN; Step 4: Prepare the negative ion polymer PSA using urea-containing products, sodium p-styrene sulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN; Step 5: Irradiate the aqueous solution of positive ion polymer PQA with ultraviolet light, irradiate the aqueous solution of negative ion polymer PSA with ultraviolet light, and then mix the two solutions to obtain composite ionic polymer micelles.

2. The method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in claim 1, characterized in that, In step 1, specifically: Under nitrogen protection, β-mercaptoethylamine, N-isopropylacrylamide, and azobisisobutyronitrile were dissolved in N,N-dimethylformamide solvent at a molar ratio of 2–2.2:100–102:1–1.

2. The mixture was stirred at 78–85 °C for 12–24 h. After the reaction was completed, the mixture was poured into ice-cold diethyl ether to precipitate, filtered, washed 2–3 times with diethyl ether, and dried under vacuum to obtain the polymer.

3. The method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in claim 1, characterized in that, Step 2 specifically involves: The polymer was dissolved in anhydrous chloroform and stirred in an ice bath at 0–4 °C until dissolved to obtain a polymer solution. 2-Ethyl isocyanate acrylic acid was dissolved in anhydrous chloroform to obtain a 2-ethyl isocyanate acrylic acid solution. Under light-protected conditions, in an ice bath at 0–4 °C, and with stirring, the 2-ethyl isocyanate acrylic acid solution was slowly added dropwise to the polymer solution over a period of 30–60 min. After the addition was complete, the ice bath was removed, and the reaction was continued to be stirred at 0–4 °C for 4–6 h. After the reaction was complete, the product was rotary evaporated, precipitated with diethyl ether, washed, and dried under vacuum to obtain the urea-containing product.

4. The method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in claim 1, characterized in that, Step 3 specifically involves: The urea-containing product, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN were dissolved in DMF and subjected to free radical polymerization at 78–85 °C for 12–24 h. After dialyzing and freeze-drying, the positive ionic polymer PQA was obtained. The mass ratio of urea-containing products, N-triethyl-(4-vinylbenzyl)ammonium chloride, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN is 1.38–2.07: 0.08–0.12: 0.04–0.06: 0.0013–0.0026.

5. The method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in claim 1, characterized in that, Step 4 specifically involves: Urea-containing products, sodium p-styrenesulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN were dissolved in DMF and subjected to free radical polymerization at 78–85 °C for 12–24 h. After dialyzing and freeze-drying, the negative ion polymer PSA was obtained. The mass ratio of urea-containing product, sodium p-styrenesulfonate, p-styrene-7-hydroxy-4-methylcoumarin, and AIBN is 1.39–2.08: 0.08–0.12: 0.03–0.05: 0.0013–0.0026.

6. The method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in claim 1, characterized in that, In step 5, the concentration ratio of negative ion polymer PSA to positive ion polymer PQA in the composite ionic polymer micelles is 0.02 to 1:

1.

7. The method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in claim 1, characterized in that, In step 5, the UV irradiation time of the aqueous solution of the positive ion polymer PQA is 2.5–29 min; the UV irradiation time of the aqueous solution of the negative ion polymer PSA is 9–50 min.

8. Temperature-responsive ionic polymer micelles prepared by the method for preparing photocrosslinkable and stabilized temperature-responsive ionic polymer micelles according to any one of claims 1-7.

9. The application of the photocrosslinkable and stabilized temperature-responsive ionic polymer micelles as described in any one of claims 1-7 in drug delivery, biosensors, and filter membranes.

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