APNO-loaded polyhydroxyethyl acrylamide hydrogel and its preparation method
The synthesis of a poly-N-hydroxyethylacrylamide hydrogel loaded with APNO addresses the limitations of traditional biomedial materials by providing enhanced antimicrobial efficacy and biocompatibility, effectively combating antibiotic-resistant bacteria with a simpler and more cost-effective production method.
Patent Information
- Application Number
- CN202310786079.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-29
- Publication Date
- 2025-07-15
- Estimated Expiration
- 2043-06-29
AI Technical Summary
Existing biomedical dressings have shortcomings in antibacterial properties and biocompatibility, especially in poor efficacy against antibiotic-resistant bacteria, and poor water solubility of photosensitizers lead to aggregation quenching.
APNO-loaded polyhydroxyethylacrylamide hydrogel was prepared, and the photosensitizer APNO was synthesized through Suzuki-Miyaura coupling reaction. Combined with ultraviolet-induced polymerization technology, hydrogel dressings with high-efficiency photodynamic antibacterial effects were prepared.
The hydrogel dressing can efficiently kill drug-resistant bacteria, provide a humid environment, promote wound healing, have high biosafety, and is simple in preparation and low-cost.
Smart Images
Figure CN116832204B_ABST
Abstract
Description
Technical Field
[0001] This specification relates to the technical field of biomedical antibacterial dressings, and particularly to a poly (2-hydroxyethyl acrylamide) hydrogel loaded with APNO and a preparation method thereof. Background Art
[0002] The skin is the first line of defense for the human body against the external environment and infectious agents. Skin wounds can severely damage the integrity of the skin barrier, thus posing a risk of local and systemic microbial infections. Skin infections are common clinically and are prone to various complications. If not treated and the wound cared for in a timely manner, the wound may develop into a serious condition such as sepsis and gangrene. Therefore, extensive medical care and effective anti-infection treatment are required after a wound occurs.
[0003] Wound dressings can prevent skin infections and dehydration and achieve lasting protection for the wound surface. Traditional dry dressings, such as cotton wool and gauze, cannot provide a moist environment and are easily adhered to the dry wound surface, ultimately causing trauma when removed. To overcome these drawbacks, researchers have developed various wet dressings. Among them, hydrogels are a particularly important type of skin dressing. As an anti-infection skin dressing, hydrogels can absorb tissue secretions, maintain a moist environment, and are conducive to wound healing. In addition, hydrogels allow gas to pass through, have good biocompatibility, and are easy to remove without causing trauma. In addition, hydrogels loaded with antibacterial drugs exhibit ideal antibacterial properties by continuously releasing drugs at the wound site, playing a crucial role in wound healing. However, in recent years, due to the misuse and abuse of antibiotics, antibiotic-resistant bacteria have become increasingly common worldwide, posing new challenges to antibacterial dressings.
[0004] In recent years, photodynamic therapy (PDT) has achieved satisfactory results in combating drug-resistant bacteria. Antibacterial photodynamic therapy can generate a large amount of reactive oxygen species (ROS) under specific laser irradiation. Excessive ROS destroys proteins, lipids, and other bioactive substances, disrupting the bacterial cell membrane structure and ultimately killing drug-resistant bacteria. However, the photosensitizers developed currently have poor water solubility and are prone to aggregation quenching. Summary of the Invention
[0005] In view of the deficiencies of the prior art, an object of this specification is to provide a poly (2-hydroxyethyl acrylamide) hydrogel loaded with APNO and a preparation method thereof, which can overcome problems such as poor antibacterial performance and poor biocompatibility of traditional biomedical materials, has a simple preparation method, the prepared hydrogel has an efficient photodynamic antibacterial effect, and is helpful for infection healing.
[0006] To achieve the above object, the embodiments of this specification provide a preparation method of a poly (2-hydroxyethyl acrylamide) hydrogel loaded with APNO, including the following steps:
[0007] Prepare compound PNO; the PNO is obtained through the Suzuki-Miyaura coupling reaction of 5-formyl-2-thiopheneboronic acid and 4-bromotriphenylamine using bis(triphenylphosphine)palladium(II) dichloride as a catalyst; the structural formula of the PNO is:
[0008] Prepare crude product A; the crude product A is obtained by reacting 4-methylpyridine and 2-bromoethanol; the structural formula of A is:
[0009] Prepare product APNO; the product APNO is obtained by reacting the crude product A with the PNO; the structural formula of the APNO is:
[0010] Prepare poly(hydroxyethyl acrylamide) hydrogel; the poly(hydroxyethyl acrylamide) hydrogel is prepared by ultraviolet-initiated polymerization of hydroxyethyl acrylamide.
[0011] Immerse the poly(hydroxyethyl acrylamide) hydrogel in the APNO solution to obtain the poly(hydroxyethyl acrylamide) hydrogel loaded with APNO.
[0012] As a preferred embodiment, in the step of preparing the compound PNO, 4-bromotriphenylamine, 4-formylphenylboronic acid, bis(triphenylphosphine)palladium(II) chloride, and potassium carbonate are mixed in tetrahydrofuran; stirred at 60 °C for 24 h, after removing the solvent, the residue is purified on a silica gel column; using dichloromethane / petroleum ether as the eluent, the compound PNO is obtained.
[0013] As a preferred embodiment, the molar ratio of 4-bromotriphenylamine, 4-formylphenylboronic acid, bis(triphenylphosphine)palladium(II) chloride, and potassium carbonate is 10:20:1:50; the volume ratio of dichloromethane to petroleum ether in the dichloromethane / petroleum ether is 2:1.
[0014] As a preferred embodiment, in the step of preparing the crude product A, 4-methylpyridine and 2-bromoethanol solution are refluxed in acetone for 24 h, the solvent is evaporated to obtain the crude product A; the molar ratio of 4-methylpyridine to 2-bromoethanol is 21:20.
[0015] As a preferred embodiment, in the step of preparing the product APNO, the compound PNO, the crude product A, and piperidine solution are refluxed in chloroform overnight to obtain the photosensitizer molecule APNO; the photosensitizer molecule APNO is purified by thin layer chromatography and eluted with dichloromethane / methanol.
[0016] As a preferred embodiment, the molar ratio of the compound PNO to the crude product A is 1:1; the volume ratio of dichloromethane to methanol in the dichloromethane / methanol is 10:1.
[0017] As a preferred embodiment, in the step of preparing the polyhydroxyethyl acrylamide hydrogel, hydroxyethyl acrylamide is dissolved in deionized water to form a mixture; α-ketoglutaric acid and N,N-methylenebisacrylamide are added to the mixture, and stirred at room temperature for 30 min; the solution is blown with nitrogen for 10 minutes to remove oxygen; ultrasonic vibration is carried out for 30 min, and centrifuged at 7000 rpm for 5 min to remove the bubbles in the solution; then the solution is transferred to a glass mold and placed under ultraviolet radiation of 365 nm and 12 W at room temperature to prepare the polyhydroxyethyl acrylamide hydrogel.
[0018] As a preferred embodiment, the molar ratio of the α-ketoglutaric acid to the hydroxyethyl acrylamide is 1:100; the addition amount of the N,N-methylenebisacrylamide is 0.03% of the hydroxyethyl acrylamide.
[0019] As a preferred embodiment, in the step of immersing the polyhydroxyethyl acrylamide hydrogel in the APNO solution, the concentration of the APNO solution is 2 μM.
[0020] The embodiments of the present specification provide a polyhydroxyethyl acrylamide hydrogel loaded with APNO, which is prepared by using the preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO described in any one of the above embodiments.
[0021] Beneficial effects:
[0022] The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO provided by this embodiment can prepare the polyhydroxyethyl acrylamide hydrogel loaded with APNO. The hydrogel has the characteristics of simulating the extracellular matrix of human cells. Compared with general biological materials, the hydrogel is more suitable for being close to the skin. Compared with general antibiotics and antibacterial materials, this novel hydrogel has multiple functions of identifying bacteria, killing bacteria, and promoting wound healing, and has multiple antibacterial targets, a broad antibacterial spectrum, and is not easy to produce drug resistance, overcoming problems such as poor biosafety, induced drug resistance, low antibacterial efficiency, poor antibacterial performance, and poor biocompatibility of general biological materials. The polyhydroxyethyl acrylamide hydrogel loaded with APNO combines photodynamic bactericidal and the characteristics of the hydrogel itself. Compared with general multifunctional antibacterial hydrogels, it has an efficient photodynamic antibacterial effect, a simpler preparation method, lower cost, more significant antibacterial effect, is more helpful for infection healing, and its biosafety has been verified.
[0023] Specific embodiments of the present invention are disclosed in detail with reference to the following description and the accompanying drawings, indicating the ways in which the principles of the present invention can be employed. It should be understood that the embodiments of the present invention are not limited in scope thereby.
[0024] Features described and / or illustrated for one embodiment can be used in the same or similar way in one or more other embodiments, combined with features in other embodiments, or substituted for features in other embodiments.
[0025] It should be emphasized that the term "comprising / including" when used herein refers to the presence of features, whole things, steps or components, but does not exclude the presence or addition of one or more other features, whole things, steps or components. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those skilled in the art, without creative efforts, other drawings can be obtained based on these drawings.
[0027] Figure 1 It is a flowchart of the steps for a method of preparing a polyhydroxyethyl acrylamide hydrogel loaded with APNO provided in this embodiment;
[0028] Figure 2 It is Figure 1 a photograph of the polyhydroxyethyl acrylamide hydrogel obtained in step S40 in ;
[0029] Figure 3 It is Figure 1 a scanning electron microscope image of the polyhydroxyethyl acrylamide hydrogel loaded with APNO obtained in step S50 in ;
[0030] Figure 4 It is Figure 1 a photo of the photodynamic antibacterial results of the polyhydroxyethyl acrylamide hydrogel loaded with APNO obtained in step S50 in against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA);
[0031] Figure 5 It is Figure 1 a photo of the treatment effect of the polyhydroxyethyl acrylamide hydrogel loaded with APNO obtained in step S50 in on the skin model infected with MRSA; where A is a photo of the skin infection wound, and B is the result of bacterial coating of the subcutaneous tissue of the infected wound;
[0032] Figure 6 It is Figure 1HE staining results of the subcutaneous tissue of the skin model infected with MRSA treated with the polyhydroxyethyl acrylamide hydrogel loaded with APNO obtained in step S50. Detailed implementation manners
[0033] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
[0034] It should be noted that when an element is referred to as being "disposed on" another element, it can be directly on the other element or there can also be another element in the middle. When an element is considered to be "connected" to another element, it can be directly connected to the other element or there may be another element in the middle at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are only for the purpose of illustration and do not represent the only implementation manner.
[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field of the present invention. The terms used in the description of the present invention herein are only for the purpose of describing specific implementation manners and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.
[0036] Please refer to Figure 1 The embodiment of the present application provides a preparation method of a polyhydroxyethyl acrylamide hydrogel loaded with APNO, including the following steps:
[0037] Step S10: Prepare compound PNO; using bis(triphenylphosphine)palladium(II) chloride as a catalyst, the PNO is obtained through the Suzuki-Miyaura coupling reaction of 5-formyl-2-thiopheneboronic acid and 4-bromotriphenylamine.
[0038] Step S20: Prepare crude product A; the crude product A is obtained by reacting 4-methylpyridine and 2-bromoethanol.
[0039] Step S30: Prepare product APNO; the crude product A reacts with the PNO to obtain the product APNO. The product APNO is a photosensitizer molecule with aggregation-induced emission (AIE) characteristics. This kind of photosensitizer molecule has excellent antibacterial effects.
[0040] Step S40: Prepare poly(hydroxyethyl acrylamide) hydrogel; use ultraviolet light to initiate the polymerization of hydroxyethyl acrylamide (HEAA) to prepare the poly(hydroxyethyl acrylamide) (PHEAA) hydrogel. The prepared poly(hydroxyethyl acrylamide) hydrogel is as shown in Figure 2 shown.
[0041] Step S50: Immerse the poly(hydroxyethyl acrylamide) hydrogel in an APNO solution to obtain a poly(hydroxyethyl acrylamide) hydrogel loaded with APNO. The scanning electron micrograph of the poly(hydroxyethyl acrylamide) hydrogel loaded with APNO is as shown in Figure 3 shown.
[0042] The preparation method of the poly(hydroxyethyl acrylamide) hydrogel loaded with APNO provided by this embodiment can prepare a poly(hydroxyethyl acrylamide) hydrogel loaded with APNO. The hydrogel has the characteristics of simulating the extracellular matrix of human cells. Compared with general biological materials, the hydrogel is more suitable for being close to the skin. Compared with general antibiotics and antibacterial materials, this novel hydrogel has multiple functions of identifying bacteria, killing bacteria, and promoting wound recovery, and has multiple antibacterial targets, a wide antibacterial spectrum, and is not easy to produce drug resistance, overcoming the problems of poor biosafety, induced drug resistance, low antibacterial efficiency, poor bacteriostatic performance, and poor biocompatibility of general biological materials. This poly(hydroxyethyl acrylamide) hydrogel loaded with APNO creatively combines photodynamic bactericidal action with the characteristics of the hydrogel itself. Compared with general multifunctional antibacterial hydrogels, it has a high-efficiency photodynamic antibacterial effect, a simpler preparation method, lower cost, more significant antibacterial effect, is more helpful for infection healing, and its biosafety has been verified.
[0043] The preparation method of the poly(hydroxyethyl acrylamide) hydrogel loaded with APNO provided by this embodiment can prepare a hydrogel loaded with an aggregation-induced emission photosensitizer (i.e., APNO) for killing drug-resistant Gram-positive bacteria. First, the synthesized APNO molecules can quickly bind to the cell membrane of Gram-positive bacteria within 3 seconds, thus distinguishing Gram-positive bacteria from Gram-negative bacteria. APNO has a high ROS generation ability, and the ROS yield is as high as 97.4%. Then, use the hydrogel to load APNO to obtain an antibacterial hydrogel wound dressing. Under light irradiation, APNO in the bacterial membrane generates a large amount of ROS, showing a high bactericidal effect on Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). More importantly, when this gel is applied to the wound surface, it can not only provide a moist environment, but also release APNO, destroy drug-resistant bacteria, achieve lasting protection, and promote wound healing. The photodynamic hydrogel dressing prepared by this preparation method can provide a very promising wound infection treatment plan, and this hydrogel can be used as a novel antibacterial material in the field of medical antibacterials.
[0044] In step S10, specifically, 4-bromotriphenylamine, 4-formylphenylboronic acid, bis(triphenylphosphine)palladium(II) chloride, and potassium carbonate are mixed in tetrahydrofuran. Then, the mixture is stirred at 60 °C for 24 h. After removing the solvent, the residue is purified on a silica gel column. Finally, using dichloromethane / petroleum ether as the eluent, the compound PNO is obtained. The structural formula of the PNO is as follows: The specific chemical reaction formula is as follows:
[0045]
[0046] Among them, the molar ratio of the 4-bromotriphenylamine, 4-formylphenylboronic acid, bis(triphenylphosphine)palladium(II) chloride, and potassium carbonate is 10:20:1:50. The volume ratio of dichloromethane to petroleum ether in the dichloromethane / petroleum ether is 2:1.
[0047] In step S20, specifically, 4-methylpyridine and 2-bromoethanol solution are refluxed in acetone for 24 h, and the solvent is evaporated to obtain the crude product A. Among them, the molar ratio of the 4-methylpyridine to the 2-bromoethanol is 21:20.
[0048] The structural formula of the A is as follows: The specific chemical reaction formula is as follows:
[0049]
[0050] In step S30, specifically, the compound PNO, the crude product A, and several drops of piperidine solution are refluxed in chloroform overnight to obtain the photosensitizer molecule APNO. The photosensitizer molecule APNO is purified by thin-layer chromatography and eluted with dichloromethane / methanol. The structural formula of the APNO is as follows: The specific chemical reaction formula is as follows:
[0051]
[0052] Among them, the molar ratio of the compound PNO to the crude product A is 1:1. The volume ratio of dichloromethane to methanol in the dichloromethane / methanol is 10:1.
[0053] In step S40, specifically, hydroxyethyl acrylamide is first dissolved in deionized water to form a mixture. α-Ketoglutaric acid and N,N-methylenebisacrylamide are added to the mixture, and the mixture is stirred at room temperature for 30 min. Then, the solution is blown with nitrogen for 10 minutes to remove oxygen. The solution is ultrasonically vibrated for 30 min and centrifuged at 7000 rpm for 5 min to remove the bubbles in the solution. Then, the solution is transferred to a glass mold and placed under ultraviolet radiation at 365 nm and 12 W at room temperature for a period of time to prepare the polyhydroxyethyl acrylamide hydrogel.
[0054] Among them, the molar ratio of the α-ketoglutaric acid to the hydroxyethyl acrylamide is 1:100. The addition amount of the N,N-methylenebisacrylamide is 0.03% of the hydroxyethyl acrylamide.
[0055] In step S50, the concentration of the APNO solution is 2 μM.
[0056] In a specific application scenario, in step S10, 4-bromotriphenylamine is 1.62 g, 5.0 mmol, 4-formylphenylboronic acid is 1.55 g, 10.0 mmol, bis(triphenylphosphine)palladium(II) chloride is 0.35 g, 0.5 mmol, and potassium carbonate is 3.44 g, 25 mmol. Tetrahydrofuran is 30 ml. In step S20, 4-methylpyridine is 0.98 g, 10.5 mmol, and 2-bromoethanol is 1.25 g, 10 mmol. Acetone is 40 ml. In step S30, PNO can be 149 mg, 0.42 mmol, compound A can be 91.1 mg, 0.42 mmol, and chloroform is 15 mL. In step S40, 1.75 g of hydroxyethyl acrylamide is dissolved in 5 ml of deionized water. 0.022 g of α-ketoglutaric acid and 0.0007 g of N,N-methylenebisacrylamide are added to the mixture.
[0057] The prepared APNO-loaded polyhydroxyethyl acrylamide hydrogel was detected for its photodynamic antibacterial activity by the agar plate method (50 mw / cm 2 white light). Staphylococcus aureus and MRSA were used as representative bacteria. The disinfected hydrogel samples were added to 48-well plates, and only the same amount of PBS was added as a blank control. 10 μL of bacterial suspension (10 8 CFU / mL) was added to their surfaces. After 4 h, the samples were respectively exposed to 50 mw / cm 2 white light irradiation for 15 min as the experimental group, and the gel without light was also used as the control group. 1 ml of sterile PBS was added to each well to resuspend the surviving bacteria. After culturing at 37 °C for 18 - 24 h, the bacterial suspension was spread on an agar plate. Each group was tested 5 times.
[0058] An MRSA skin infection model was established in rats. Then, the wound was irradiated with white light at a power of 50 mw / cm 2 for 30 minutes. On the 3rd and 7th days after the operation, the entire wound and the adjacent normal skin were collected. The infected tissues were separated and homogenized with physiological saline. The homogenate was diluted 1000 times with physiological saline. 100 μL of the bacterial suspension was sprayed on an LB agar plate and incubated at 37 °C. The other tissues were fixed in 4% paraformaldehyde for histological analysis. And the wound was photographed, as shown in Figure 5 Figure A.
[0059] The antibacterial effect diagrams of the polyhydroxyethyl acrylamide hydrogel loaded with APNO prepared by the preparation method of the present invention against Staphylococcus aureus and MRSA are as Figure 4 shown. As can be seen from Figure 4 , the hydrogel prepared by the preparation method of the present invention has a high bactericidal effect against Staphylococcus aureus and MRSA. The antibacterial effect diagrams of the polyhydroxyethyl acrylamide hydrogel loaded with APNO prepared by the preparation method of the present invention against the MRSA skin infection model are as Figure 5 and Figure 6 shown. As can be seen from Figure 5 and Figure 6 , the hydrogel prepared by the preparation method of the present invention has a significant therapeutic effect on MRSA skin infection.
[0060] An embodiment of the present invention also provides a polyhydroxyethyl acrylamide hydrogel loaded with APNO, which is prepared by using the preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO described in any one of the above embodiments.
[0061] In this embodiment, the polyhydroxyethyl acrylamide hydrogel loaded with APNO can solve the technical problems solved by the embodiment of its preparation method, and correspondingly achieve the technical effects of the embodiment of its preparation method. Specifically, this application will not elaborate herein.
[0062] It should be noted that in the description of this specification, the terms "first", "second", etc. are only used for descriptive purposes and to distinguish similar objects, and there is no sequence between them, nor can they be understood as indicating or implying relative importance. In addition, in the description of this specification, unless otherwise specified, the meaning of "a plurality" is two or more.
[0063] Any numerical value cited herein includes all values from the lower value to the upper value increasing by one unit between the lower limit value and the upper limit value, as long as there is an interval of at least two units between any lower value and any higher value. For example, if it is stated that the value of the number of components or process variables (such as temperature, pressure, time, etc.) is from 1 to 90, preferably from 20 to 80, more preferably from 30 to 70, then the purpose is to illustrate that values such as 15 to 85, 22 to 68, 43 to 51, 30 to 32, etc. are also explicitly listed in this specification. For values less than 1, a unit is appropriately considered to be 0.0001, 0.001, 0.01, 0.1. These are only examples of what is intended to be clearly expressed, and it can be considered that all possible combinations of the numerical values listed between the lowest value and the highest value are explicitly described in this specification in a similar manner.
[0064] Unless otherwise indicated, all ranges include the endpoints and all numbers between the endpoints. The term "about" or "approximate" used in connection with a range is applicable to both endpoints of the range. Thus, "about 20 to 30" is intended to cover "about 20 to about 30", including at least the specified endpoints.
[0065] All articles and references disclosed, including patent applications and publications, are incorporated herein by reference for various purposes. The term "consisting essentially of" in describing a combination shall include the identified elements, ingredients, components or steps as well as other elements, ingredients, components or steps that do not materially affect the basic novel characteristics of the combination. The use of the terms "comprising" or "including" to describe the combinations of elements, ingredients, components or steps herein also contemplates embodiments consisting essentially of these elements, ingredients, components or steps. By using the term "may" herein, it is intended that any of the attributes described as "may" include be optional.
[0066] A plurality of elements, ingredients, components or steps can be provided by a single integrated element, ingredient, component or step. Alternatively, a single integrated element, ingredient, component or step can be divided into separate plural elements, ingredients, components or steps. The disclosure of the articles "a" or "an" used to describe an element, ingredient, component or step is not intended to exclude other elements, ingredients, components or steps.
[0067] It should be understood that the above description is for illustrative purposes and not for limitation. Many embodiments and many applications other than the examples provided will be apparent to those skilled in the art upon reading the above description. Therefore, the scope of the present teachings should not be determined with reference to the above description, but should be determined with reference to the appended claims and the full scope of equivalents to which those claims are entitled. For completeness, all articles and references, including patent applications and published disclosures, are incorporated herein by reference. The omission of any aspect of the subject matter disclosed herein in the foregoing claims is not intended to forego that subject matter, nor should the inventors be regarded as not having considered that subject matter to be a part of the disclosed inventive subject matter.
Claims
1. A preparation method of a polyhydroxyethyl acrylamide hydrogel loaded with APNO, characterized in that, It includes the following steps: Prepare compound PNO; use bis(triphenylphosphine)palladium(II) dichloride as a catalyst to obtain the PNO through the Suzuki-Miyaura coupling reaction of 5-formyl-2-thiopheneboronic acid and 4-bromotriphenylamine; the structural formula of the PNO is: Prepare crude product A; obtain the crude product A by reacting 4-methylpyridine and 2-bromoethanol; the structural formula of A is: Prepare product APNO; react the crude product A with the PNO to obtain the product APNO; the structural formula of the APNO is: Prepare poly(hydroxyethyl acrylamide) hydrogel; use ultraviolet light to initiate the polymerization of hydroxyethyl acrylamide to prepare the poly(hydroxyethyl acrylamide) hydrogel; Immerse the poly(hydroxyethyl acrylamide) hydrogel in the APNO solution to obtain the poly(hydroxyethyl acrylamide) hydrogel loaded with APNO.
2. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 1, characterized in that, In the step of preparing compound PNO, mix 4-bromotriphenylamine, 4-formylphenylboronic acid, bis(triphenylphosphine)palladium(II) chloride, and potassium carbonate in tetrahydrofuran; stir at 60 °C for 24 h, remove the solvent, and purify the residue on a silica gel column; use dichloromethane / petroleum ether as the eluent to obtain the compound PNO.
3. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 2, wherein, The molar ratio of 4-bromotriphenylamine, 4-formylphenylboronic acid, bis(triphenylphosphine)palladium(II) chloride, and potassium carbonate is 10:20:1:50; the volume ratio of dichloromethane to petroleum ether in the dichloromethane / petroleum ether is 2:
1.
4. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 1, characterized in that, In the step of preparing crude product A, reflux 4-methylpyridine and 2-bromoethanol solution in acetone for 24 h, evaporate to remove the solvent to obtain the crude product A; the molar ratio of 4-methylpyridine to 2-bromoethanol is 21:
20.
5. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 1, characterized in that, In the step of preparing product APNO, reflux the compound PNO, the crude product A, and piperidine solution in chloroform overnight to obtain the photosensitizer molecule APNO; The photosensitizer molecule APNO is purified by thin layer chromatography and eluted with dichloromethane / methanol.
6. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 5, characterized in that, The molar ratio of the compound PNO to the crude product A is 1:1; the volume ratio of dichloromethane to methanol in the dichloromethane / methanol is 10:
1.
7. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 1, characterized in that, In the step of preparing the poly(hydroxyethyl acrylamide) hydrogel, dissolve hydroxyethyl acrylamide in deionized water to form a mixture; add α-ketoglutaric acid and N,N-methylenebisacrylamide to the mixture and stir at room temperature for 30 min; blow the solution with nitrogen for 10 minutes to remove oxygen; ultrasonically vibrate for 30 min and centrifuge at 7000 rpm for 5 min to remove the bubbles in the solution; Then transfer the solution to a glass mold and place it under ultraviolet radiation of 365 nm and 12 W at room temperature to prepare the poly(hydroxyethyl acrylamide) hydrogel.
8. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 7, characterized in that, The molar ratio of α-ketoglutaric acid to hydroxyethyl acrylamide is 1:100; the addition amount of N,N-methylenebisacrylamide is 0.03% of hydroxyethyl acrylamide.
9. The preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO according to claim 1, characterized in that, In the step of immersing the poly(hydroxyethyl acrylamide) hydrogel in the APNO solution, the concentration of the APNO solution is 2 μM.
10. A polyhydroxyethylacrylamide hydrogel loaded with APNO, characterized in that, It is prepared by using the preparation method of the polyhydroxyethyl acrylamide hydrogel loaded with APNO as described in any one of claims 1-9.