Rbpda hydrogel precursors for treating skin infections, methods of making and uses thereof

Abstract

The application discloses an RB@PDA hydrogel precursor for treating skin infection, a preparation method and application, and belongs to the technical field of biomedical materials. The RB@PDA hydrogel precursor comprises a sodium alginate aqueous solution and RB@PDA nanoparticles dispersed in the sodium alginate aqueous solution, wherein the RB@PDA nanoparticles are prepared through a hydrothermal synthesis reaction of a dopamine precursor and rose Bengal under alkaline conditions. 2+ The material can realize photothermal therapy and photodynamic therapy under 808 nm near-infrared laser irradiation, effectively destroy the structure of bacteria and biofilms, and has excellent antibacterial performance. The hydrogel has good biocompatibility and can significantly accelerate the healing process of bacterial infection wounds.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical materials, and particularly relates to an RB@PDA hydrogel precursor for treating skin infection, a preparation method and application. BACKGROUND

[0002] Chronic refractory skin infections (such as diabetic foot ulcers and skin abscesses) usually heal slowly, which easily leads to repeated hospitalization of patients. At present, traditional antibiotic therapy is facing the problems of bacterial drug resistance and systemic side effects in clinical practice. In addition, pathogenic bacteria are prone to form biofilms after infection, and this protective matrix composed of extracellular polymers can block the penetration of antibiotics, significantly weakening the effect of traditional antibacterial therapy.

[0003] To solve the above problems, various new therapies and functional dressings are explored for antibacterial therapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT). PDT uses photosensitizers to produce reactive oxygen species (ROS) under specific wavelength light, which attacks bacteria structure through multiple targets, has the advantages of small trauma and not easy to induce drug resistance, and is considered as a promising antibacterial strategy. However, its efficacy is highly dependent on oxygen concentration, so its treatment effect is limited in the hypoxic environment of bacterial infection. PTT can convert light energy into heat energy through near-infrared light, and physically destroy bacteria and biofilms through local high temperature, which is suitable for complementing PDT. However, PTT still has some limitations in practical application: improper temperature control may damage surrounding healthy tissues, and some light materials may induce local inflammation in the aggregated state. Therefore, it is particularly important to construct a safer and more controllable photothermal material system and dosage parameters. In addition, whether it is PTT or PDT, the photothermal agent or photosensitizer is easily removed by the body during local drug delivery, making it difficult to maintain an effective concentration at the infection site, which limits the treatment effect.

[0004] In the aspect of wound dressing, sodium alginate (SA) can form a hydrogel with Ca 2+ Crosslinking occurs under mild conditions to form an in-situ hydrogel, which has attracted extensive attention. The gelation kinetics and mechanical properties of the material can be flexibly adjusted by regulating the type, concentration and diffusion conditions of metal ions. Such hydrogels have good liquid absorption capacity, can create a moist healing environment, and have hemostatic and low adhesion properties. Its in-situ gelation property enables it to closely adhere to irregular wounds, reducing secondary damage during replacement and being beneficial to wound repair.

[0005] In summary, the existing traditional anti-infection treatment for chronic infected wounds has some problems that are difficult to overcome, such as bacterial drug resistance and systemic side effects. Therefore, it is of great clinical significance and application value to develop a new product and a corresponding preparation method that can achieve local precise drug delivery, is not easy to produce drug resistance, and has lower toxic and side effects. SUMMARY

[0006] The present application aims at solving the problems of the prior art and providing an RB@PDA hydrogel precursor for treating skin infection, a preparation method and application thereof.

[0007] The specific technical solutions adopted by the present application are as follows:

[0008] In a first aspect, the present application provides an RB@PDA hydrogel precursor for treating skin infection, which comprises a sodium alginate aqueous solution and RB@PDA nanoparticles dispersed therein; the RB@PDA nanoparticles are prepared by hydrothermal synthesis reaction of a dopamine precursor and rose Bengal under alkaline conditions; the average particle size of the RB@PDA nanoparticles is 50-200 nm.

[0009] In a second aspect, the present application provides a preparation method of the RB@PDA hydrogel precursor for treating skin infection, which is specifically as follows:

[0010] The dopamine precursor and rose Bengal are subjected to hydrothermal synthesis reaction under alkaline conditions, and the reaction product is centrifuged, washed and dried to obtain RB@PDA nanoparticles; the RB@PDA nanoparticles are dispersed in a sodium alginate aqueous solution to form the RB@PDA hydrogel precursor.

[0011] Preferably, the dopamine precursor is dopamine hydrochloride or levodopa.

[0012] Preferably, in the hydrothermal synthesis reaction system, the mass ratio of rose Bengal to dopamine precursor is 1: (1-3); the hydrothermal synthesis reaction conditions are controlled as follows: pH is 8.5-11, reaction is carried out at 40-60℃ for 2-4 hours.

[0013] Preferably, the mass concentration of the sodium alginate aqueous solution is 0.5-2%; the final concentration of the RB@PDA nanoparticles in the sodium alginate aqueous solution is 50-200 μg / mL.

[0014] In a third aspect, the present application provides an RB@PDA hydrogel precursor prepared according to the preparation method of the second aspect.

[0015] In a fourth aspect, the present application provides an application of the RB@PDA hydrogel precursor in preparing a light-responsive synergistic antibacterial hydrogel; the RB@PDA hydrogel precursor of the first or second aspect is in-situ crosslinked in a calcium ion-containing crosslinking agent environment to form a light-responsive synergistic antibacterial hydrogel with a three-dimensional gel network structure; the light-responsive synergistic antibacterial hydrogel simultaneously produces photothermal effect and photodynamic effect under near-infrared light irradiation to realize synergistic antibacterial effect.

[0016] As preferred, the near-infrared wavelength is 800-820 nm.

[0017] As preferred, the calcium ion concentration in the crosslinking agent is 1-3%.

[0018] As preferred, the light-responsive synergistic antibacterial hydrogel is used for preparing a pharmaceutical composition for preventing and / or treating bacterial wound infection and its concurrent biofilm-related lesions; preferably, the lesions include diabetic foot ulcers, skin abscesses, and postoperative infected wounds.

[0019] Compared with the prior art, the present application has the following beneficial effects:

[0020] 1. Near-infrared-excited synergistic antibacterial strategy: PDA has a wide and strong absorption at 808 nm, has excellent light-heat conversion efficiency, and can achieve effective photothermal therapy. Its rich catechol structure can efficiently load photosensitizer Rose Bengal through π-π stacking and hydrogen bonding for photodynamic sterilization, solving the problem of good water solubility and easy leakage of RB. In addition, the local heat generated by PDA can enhance the permeability of bacterial cell membranes, thereby promoting the entry of reactive oxygen species and killing efficiency, achieving the synergistic bactericidal effect of photothermal and photodynamic, especially in low-oxygen or chronic infected wounds.

[0021] 2. Removal of metal ions to avoid toxic side reactions: The present application uses polydopamine to load Rose Bengal (RB@PDA) structure to construct a light-responsive nanosystem, without introducing iron-based or other transition metal ions, avoiding metal-induced Fenton side reactions and potential chronic toxicity problems, and being safer, suitable for long-term dressing scenarios such as infected wounds.

[0022] 3. Intelligent response in situ gelation mechanism: Using calcium ions in the interstitial fluid of the skin tissue as a natural crosslinking agent, the sol-gel transition of sodium alginate solution can be completed in about 1 minute. RB@PDA nanoparticles are stably dispersed and fixed in the three-dimensional gel network formed by sodium alginate, which can closely adhere to the surface of irregular wounds. Compared with traditional solution or sprayed photosensitizers, the present application can achieve long-term retention at the administration site, effectively avoiding the dilution or passive removal of components by wound exudate. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 Surface morphology diagram of RB@PDA nanoparticles prepared for Example 1 under scanning electron microscope (SEM);

[0024] Figure 2 Particle size and distribution diagram of RB@PDA nanoparticles prepared for Example 1 under dynamic light scattering (DLS);

[0025] Figure 3 A comparison chart of the photodynamic effect in Example 2;

[0026] Figure 4 A comparison chart of the bactericidal rate of different treatment groups under immunofluorescence staining in Example 2;

[0027] Figure 5 A comparison chart of the cell survival rate of different treatment groups under immunofluorescence staining in Example 2;

[0028] Figure 6 A surface morphology chart of the hydrogel obtained in Example 3 under scanning electron microscope (SEM);

[0029] Figure 7 A scanning electron microscope chart of the antibacterial performance of different treatment groups on Staphylococcus aureus in Example 4;

[0030] Figure 8 A thermal imaging data chart of mice in different treatment groups in Example 5;

[0031] Figure 9 A skin infection site repair result chart of mice in different treatment groups in Example 6. DETAILED DESCRIPTION

[0032] The advantages and various effects of the present application will be more clearly presented from the specific embodiments and examples below. The technical features of each embodiment in the present application can be combined accordingly without conflict. Those skilled in the art should understand that these specific embodiments and examples are used to illustrate the present application, not to limit the present application.

[0033] Throughout the specification, unless otherwise specifically indicated, the terms used herein are to be understood as having the meanings commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art to which the present application belongs. If there is a conflict, the present specification takes precedence.

[0034] Unless otherwise specifically indicated, the various raw materials, reagents, instruments and equipment used in the present application can be purchased from the market or obtained by existing methods.

[0035] The RB@PDA hydrogel precursor, preparation method and application of the present application will be described in detail below in combination with examples and experimental data.

[0036] Example 1: Preparation of RB@PDA hydrogel precursor

[0037] (1) Preparation of RB@PDA nanoparticles

[0038] 20 mg of dopamine hydrochloride and 10 mg of Bengal rose red were co-dissolved in 10 mL of deionized water. The solution was slowly stirred with a magnetic stirrer for 5 minutes until it was completely dissolved and formed a clear, transparent solution. Then, 84 μL of 1 mol / L NaOH solution was added to adjust the pH of the reaction system to alkaline.

[0039] Turn on the heating function of the magnetic stirrer and increase the speed to 600-1000 rpm to heat the solution to 50°C, keeping it in the dark. Carry out the hydrothermal reaction at 50°C for 3 hours. During this time, the reaction system should gradually change from a clear solution to a brownish-red color and become a colloidal dispersion.

[0040] The suspension was transferred to centrifuge tubes and centrifuged at 12,000 rpm for 10 minutes. After separation, the mixture was washed several times to remove excess dopamine hydrochloride and Bengal rose red, and finally dried to obtain RB@PDA nanoparticles.

[0041] In this embodiment, the mass ratio of dopamine hydrochloride to Bengal rose red is 2:1, and the mass of added NaOH accounts for approximately 3.36‰ of the total mass of the original reaction system.

[0042] After appropriate dilution, the surface morphology of the prepared RB@PDA nanoparticles was observed under a scanning electron microscope. Figure 1 As shown, the particle morphology is approximately spherical, with a single particle diameter of about 100 nm. The obtained particles are uniformly distributed and dispersed among each other, with no obvious aggregation observed.

[0043] Dynamic light scattering detection was performed on RB@PDA nanoparticles, and the results are as follows: Figure 2 As shown, the particle size distribution peaks are concentrated and exhibit a single peak shape, without multi-peak or tailing phenomena, indicating that the particle distribution in the system is relatively uniform. The average hydrated particle size of the RB@PDA nanoparticles is approximately 130 nm, and the polydispersity index (PDI) is 0.126, significantly lower than 0.2, indicating that the nanoparticles possess good dispersibility and colloidal stability.

[0044] (2) Preparation of RB@PDA hydrogel precursor

[0045] Add 100 mg of sodium alginate to 10 mL of deionized water and stir with a magnetic stirrer at room temperature until completely dissolved to obtain a 1% sodium alginate aqueous solution. Store at 4°C, protected from light, for later use.

[0046] Weigh 1 mg of the RB@PDA nanoparticles prepared in the above steps and add them to an aqueous solution of sodium alginate. Stir slowly with a magnetic stirrer until the final concentration of RB@PDA nanoparticles reaches 100 μg / mL, thus obtaining an injectable RB@PDA hydrogel precursor.

[0047] Example 2: Performance test of RB@PDA nanoparticles

[0048] (1) Photodynamic effect test

[0049] The RB@PDA nanoparticles prepared in Example 1 were taken, and 1,3-diphenylisobenzofuran (DPBF) was used as an indicator to detect the photodynamic effect of the RB@PDA nanoparticles, i.e., the singlet oxygen (O2) generation ability, according to the following steps: 1

[0050] The RB@PDA nanoparticle solution was diluted with deionized water to 100 μg / mL and stood for use. A 20 μL pipette was taken to take 1.5 mg / mL of DPBF solution and added to 1 mL of the above RB@PDA nanoparticle deionized water dispersion. Subsequently, the dispersion was irradiated with laser of 808 nm wavelength and 1 W / cm 2 intensity for 5 minutes in a UV spectrophotometer. During the irradiation, the absorption spectrum of the oxidized DPBF solution was recorded every 1 minute, and the detection wavelength was selected as 300-600 nm to detect the generation of singlet oxygen. The control group did not add RB@PDA nanoparticles, and the results are shown in Figure 3 .

[0051] According to Figure 3 , the absorbance of the system added with RB@PDA nanoparticles (RB@PDA NPs) decreased significantly at 420 nm, and the absorbance decreased by about 24.6% within 5 minutes. This is due to the singlet oxygen generated by the nanoparticles under light irradiation which effectively oxidizes DPBF. In contrast, the control group (NC) showed no significant change. The results demonstrate that the synthesized RB@PDA nanoparticles have good and efficient photodynamic activity.

[0052] (2) In vitro antibacterial ability test

[0053] The RB@PDA nanoparticles prepared in Example 1 were taken, and Staphylococcus aureus (S. aures) was used as a representative to study the antibacterial effect. The specific steps are as follows:

[0054] First, the RB@PDA nanoparticle dispersion was sterilized by passing through a 0.22 μm sterile filter membrane. Then, the strain was inoculated into tryptone soy broth medium, and cultured in a bacterial constant temperature shaker at 37°C for 12 hours to the logarithmic growth phase. The logarithmic growth phase bacteria were diluted with PBS buffer to a concentration of 1×10 7 CFU / mL for use. Subsequently, the hydrogel was irradiated with laser of 808 nm wavelength and 0.5 W / cm 2 intensity for 5 minutes. ​

[0055] Then, the bacteria dilution solution was added with the aforementioned sterilized RB@PDA nanoparticles to a final concentration of 100 μg / mL, and placed in a constant temperature shaker at 37°C. The control group was added with the same amount of deionized water without nanoparticles. Finally, 500 μL of the treated suspension was taken and dyed according to the instructions of the bacterial live / dead staining kit (SYTO 9 / PI). A confocal microscope was used to excite at a wavelength of 488 nm (SYTO 9, live bacteria, green) and 561 nm (PI, dead bacteria, red), and collect 500-550 nm and 580-650 nm channels. The bacterial count was quantified by ImageJ, and the bactericidal rate was calculated. The results are shown in Figure 4 .

[0056] The results are shown in Figure 4 . The bactericidal rate of the group added with RB@PDA nanoparticles was more than 94%, while the bactericidal rate of the group without nanoparticles was less than 10%, with a significant difference between the groups (P<0.001). This indicates that RB@PDA nanoparticles have antibacterial effect.

[0057] (3) In vitro safety detection

[0058] RB@PDA nanoparticles prepared in Example 1 were obtained, and NIH-3T3 cells (fibroblasts) and HUVEC cells (vascular endothelial cells) were selected as model cells to study the safety of the application. The specific steps are as follows:

[0059] First, the RB@PDA nanoparticle dispersion was sterilized by passing through a 0.22 μm sterile filter membrane, and then added to complete culture medium to a concentration of 100 μg / mL. Logarithmic growth phase NIH-3T3 cells and HUVEC cells were mixed and added to the corresponding complete culture medium, and inoculated into a 6-well plate and placed in a constant temperature incubator at 37°C and 5% CO2 concentration. Then, when the cell growth density was about 50%, the culture medium was discarded, and the complete culture medium containing RB@PDA nanoparticles was added and incubated with the cells for 24 hours under the same culture conditions. Finally, as in step (2) above, the cells were dyed with a cell live / dead staining kit (Calcein-AM / PI), and the cell state was observed, and the cell survival rate was calculated. The results are shown in Figure 5 .

[0060] As shown in Figure 5 , Live / Dead showed a green color as the main color, and the red / green ratio did not significantly increase. In the two groups with and without the addition of RB@PDA nanoparticles, the survival rates of both NIH-3T3 and HUVEC cells were greater than 85%, and there was no significant difference between the groups (P>0.05). This indicates that RB@PDA nanoparticles have no significant effect on cell survival.

[0061] Example 3: Preparation of photoresponsive synergistic antibacterial hydrogel from RB@PDA hydrogel precursor

[0062] The calcium ion concentration in the interstitial fluid of normal human skin is approximately 2%. Therefore, calcium chloride was weighed and added to deionized water to prepare an aqueous solution containing 2% calcium chloride. An appropriate amount of the hydrogel precursor prepared in Example 1 was then injected into the solution to obtain a shaped hydrogel.

[0063] like Figure 6 As shown, after the hydrogel was freeze-dried, it was observed under a scanning electron microscope and found that it cross-linked to form a three-dimensional porous structure, indicating that the hydrogel precursor can solidify in response to calcium ions to obtain the hydrogel.

[0064] Example 4: Photodynamic Effect Test of RB@PDA Hydrogel

[0065] To simulate the antibacterial effect of hydrogels under physiological conditions, the photodynamic effect of RB@PDA hydrogels was tested according to the following steps:

[0066] First, as described in step (2) of Example 2, a concentration of 1×10⁻⁶ is obtained. 7 The bacteria were in the logarithmic growth phase at CFU / mL. Next, sterile glass slides were placed in 6-well plates as an attachment substrate, and an equal amount of the bacterial strain was inoculated and incubated statically at 37°C.

[0067] To investigate the effect of RB@PDA hydrogel on immature biofilms (containing calcium ions), RB@PDA hydrogel precursor was directly added to the well plates at a concentration of 1000 μg / mL. After 3 minutes of crosslinking, the samples were analyzed using a UV spectrophotometer at a wavelength of 808 nm and a wavelength of 0.5 W / cm². 2 Irradiate the hydrogel with high intensity laser for 5 minutes, and continue culturing for 48 hours.

[0068] To investigate the effect of RB@PDA hydrogel on mature biofilms (containing calcium ions), RB@PDA hydrogel precursor was added to 6-well plates cultured for 24 hours to a final concentration of 1000 μg / mL. After crosslinking for 3 minutes, the samples were analyzed using a UV spectrophotometer at 808 nm wavelength and 0.5 W / cm². 2 The hydrogel was irradiated with a high-intensity laser for 5 minutes and then cultured for another 24 hours. A control group was set up, following the same grouping method as in Example 2. After the experiment, the samples were gently washed and fixed, then dehydrated using a gradient method and observed under a scanning electron microscope. The results are as follows: Figure 7 As shown.

[0069] according to Figure 7As shown, in the immature biofilm stage, after RB@PDA hydrogel treatment, the bacterial surface adhesion was significantly weakened, and the biofilm structure was difficult to form; in the mature biofilm stage, the RB@PDA hydrogel treatment group showed obvious biofilm rupture, bacterial shrinkage and shedding phenomena, while the control group still maintained a dense and complete three-dimensional structure. This shows that the RB@PDA nanoparticles in the hydrogel have a dual effect on bacterial biofilm, both inhibiting its early formation and destroying the established mature biofilm structure, proving that the material has application potential in both preventing and treating biofilm-related infections.

[0070] Example 5: In vivo photothermal effect test of photoresponsive synergistic antibacterial hydrogel

[0071] The RB@PDA hydrogel precursor prepared in Example 1 was obtained, and the photothermal effect was detected according to the following steps:

[0072] The RB@PDA hydrogel precursor was subjected to sterile treatment and stored in the dark.

[0073] A number of 8-week-old SPF female BALB / c mice were obtained, and the temperature and humidity and circadian rhythm were routinely raised. After adapting to the environment, the mouse back skin was shaved, and the mice were divided into hydrogel and control groups by 8 mice per group by random number method. The mice were anesthetized by inhaling isoflurane, and 50 μL of hydrogel precursor containing or not containing RB@PDA nanoparticles was injected intradermally into the back of the mice. Visible superficial wheals were observed, and baseline data were recorded using a live imaging instrument. After waiting for 2 minutes, a near-infrared laser was taken, the wavelength was set to 808 nm, the intensity was set to 0.5 W / cm 2 , the distance was set to 5 cm, and the injection site was irradiated for 10 minutes. At the same time, the thermal imaging data were recorded using a live imaging instrument, and the data were continuously collected for 10 minutes. The results are shown in Figure 8

[0074] According to Figure 8 , the control group (NC) showed only a slight temperature rise after 808 nm near-infrared light irradiation, and the skin surface temperature was about 35-36℃ at 10 minutes, which was always lower than the effective temperature threshold of photothermal antibacterial (≥45℃), indicating that simple light irradiation would not cause significant temperature rise. The RB@PDA hydrogel injection group showed obvious photothermal response under the same light irradiation conditions, with the temperature rising to about 40℃ at 2 minutes of light irradiation, further rising to about 45℃ at 4-6 minutes, and rising to about 50-53℃ at 8-10 minutes. This temperature range is in the mild photothermal treatment window, which is sufficient to destroy bacteria and biofilm, but is lower than the threshold that causes normal tissue charring or thermal damage (>55℃), proving that the material can be used for photoresponsive synergistic antibacterial.

[0075] Example 6: Infection skin repair experiment of photoresponsive synergistic antibacterial hydrogel ​

[0076] The RB@PDA hydrogel precursor prepared in Example 1 was obtained, and its ability to promote the repair of infected skin was detected in vivo in mice according to the following steps:

[0077] First, the BALB / c mice were obtained, grouped and shaved according to the method of Example 5. According to the method of step (2) of Example 2, the logarithmic growth phase of Staphylococcus aureus was obtained, and the logarithmic growth phase of bacteria was diluted with PBS buffer to a concentration of 10 8 CFU / mL.

[0078] Then, after isoflurane inhalation anesthesia, the surface skin was disinfected, and 50 μL of the bacterial dilution was injected intradermally into each mouse by a syringe. After 24 h of infection, the hydrogel precursor containing or not containing RB@PDA nanoparticles was injected intradermally into the infected skin of the two groups of mice. After waiting for 2 minutes, a near-infrared laser was taken, and the wavelength was set to 808 nm, the intensity was set to 0.5 W / cm 2 , the distance was set to 5 cm, and the infected skin was irradiated for 5 minutes. Thereafter, the infected site was irradiated once a day, and the irradiation was continued until the 3rd day after infection. From the beginning to the 11th day after infection, the infection and healing of the skin of the mice were continuously observed and recorded, and the results are shown in Figure 9 .

[0079] According to Figure 9 , the control group (NC) that did not receive RB@PDA hydrogel treatment had a slow wound contraction throughout the observation period, and obvious necrotic scab and red and swollen inflammatory reaction could still be seen on the 7th day, and it was not completely closed until the 11th day, indicating that the infection microenvironment persisted and the spontaneous healing ability was weak. In contrast, the treatment group receiving RB@PDA hydrogel loading could observe that the wound was significantly reduced, the necrotic tissue and exudation gradually decreased, and the wound edge contracted more rapidly from the third day. By the 7th to 9th day, the wound was basically covered with epithelium and entered the tissue remodeling stage, and by the 11th day, it was close to complete healing.

[0080] In summary, the RB@PDA nanoparticles constructed in the application have uniform size and good dispersibility, can efficiently generate reactive oxygen species under light condition, and exhibit significant photothermal response characteristics. In vitro experiments demonstrate that the nanoparticles have strong bactericidal effect on Staphylococcus aureus. After being uniformly embedded in sodium alginate to form an injectable hydrogel precursor, the nanoparticles can rapidly generate mild and controllable local heating under near-infrared light irradiation, while maintaining good biocompatibility. In vitro experiments demonstrate that the application can effectively inhibit early biofilm formation and destroy mature biofilm structure. In the living body infection model, the hydrogel can in situ gel and continuously exert the combined photothermal / photodynamic antibacterial effect, significantly reduce the infection load, promote epithelialization and tissue repair on the wound edge, and significantly accelerate wound healing, without secondary infection or thermal damage. The above results show that the material of the application not only has excellent in vitro antibacterial and biofilm removal capacity, but also has dual functions of in vivo anti-infection and wound healing promotion, providing a safe, controllable and efficient strategy for the treatment of chronic or complex infected wounds.

[0081] The above-described embodiments are only a preferred scheme of the application, and are not intended to limit the application. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the application. Therefore, any technical scheme obtained by equivalent replacement or equivalent transformation falls within the protection scope of the application.

Claims

1. A method for preparing an RB@PDA hydrogel precursor for treating skin infections, characterized in that, Specifically as follows: Dopamine precursor and Bengal rose red were subjected to a hydrothermal synthesis reaction under alkaline conditions. The reaction product was centrifuged, washed and dried to obtain RB@PDA nanoparticles. The RB@PDA nanoparticles were dispersed in an aqueous sodium alginate solution to form an RB@PDA hydrogel precursor. The dopamine precursor is dopamine hydrochloride; In the hydrothermal synthesis reaction system, the mass ratio of Bengal rose red to dopamine precursor is 1:(1~3); the hydrothermal synthesis reaction conditions are controlled as follows: pH 8.5~11, reaction is carried out at 40~60℃ for 2~4 hours.

2. The method for preparing the RB@PDA hydrogel precursor according to claim 1, characterized in that, The mass concentration of the sodium alginate aqueous solution is 0.5-2%; the final concentration of the RB@PDA nanoparticles in the sodium alginate aqueous solution is 50-200 μg / mL.

3. An RB@PDA hydrogel precursor prepared according to the preparation method described in claim 1 or 2.

4. The application of an RB@PDA hydrogel precursor in the preparation of a photoresponsive synergistic anti-Staphylococcus aureus hydrogel, characterized in that, The RB@PDA hydrogel precursor of claim 3 is crosslinked in situ in an environment containing a calcium ion crosslinking agent to form a photoresponsive synergistic anti-Staphylococcus aureus hydrogel with a three-dimensional gel network structure; the photoresponsive synergistic anti-Staphylococcus aureus hydrogel generates both photothermal and photodynamic effects under near-infrared light irradiation to achieve synergistic anti-Staphylococcus aureus.

5. The application of the RB@PDA hydrogel precursor according to claim 4 in the preparation of a photoresponsive synergistic anti-Staphylococcus aureus hydrogel, characterized in that, The wavelength of the near-infrared light is 800~820 nm.

6. The application of the RB@PDA hydrogel precursor according to claim 4 in the preparation of a photoresponsive synergistic anti-Staphylococcus aureus hydrogel, characterized in that, The calcium ion concentration in the crosslinking agent is 1-3%.

7. The application of the RB@PDA hydrogel precursor according to claim 4 in the preparation of a photoresponsive synergistic anti-Staphylococcus aureus hydrogel, characterized in that, The photoresponsive synergistic anti-Staphylococcus aureus hydrogel is used to prepare pharmaceutical compositions for the prevention and / or treatment of bacterial wound infections and their associated biofilm-related lesions.

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