Ruthenium complex-loaded carbon nitride modified up-conversion nanoparticles, preparation method thereof and application of ruthenium complex-loaded carbon nitride modified up-conversion nanoparticles in preparation of drugs for treating fungal biofilm infection

Abstract

The invention discloses ruthenium complex-loaded carbon nitride modified up-conversion nanoparticles, a preparation method thereof and an application of the ruthenium complex-loaded carbon nitride modified up-conversion nanoparticles in preparation of a medicine for treating fungal biofilm infection.The preparation process comprises the steps that lanthanide doped up-conversion nanoparticles UCNP are coated with double silicon dioxide layers, then hydrothermal etching treatment is performed, and the ruthenium complex-loaded carbon nitride modified up-conversion nanoparticles are obtained; the lanthanide doped up-conversion nanoparticles UCNP (at) hmSiO2 with a hollow silicon dioxide outer layer are obtained; the UCNP (at) hmSiO2 and cyanamide are calcined for a reaction, cyanamide is condensed in a silicon dioxide layer to form carbon nitride, then silicon dioxide is etched, and carbon nitride modified lanthanide doped up-conversion nanoparticles UCNP (at) g-C3N4 are obtained; and adding a ruthenium complex to react with the UCNP (at) g-C3N4, so as to obtain the ruthenium complex loaded carbon nitride modified up-conversion nanoparticles UCNP (at) g-C3N4-Ru. The preparation method has the advantages that the UCNP (at) g-C3N4-Ru can generate reactive oxygen species (ROS) under ultrasonic and illumination to effectively loosen a fungal biofilm, so that a medicine is promoted to permeate into fungi, the fungi are efficiently killed, and the biofilm is damaged.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, in particular to a drug for treating fungal biofilm infection. Background Art

[0002] Fungal infection is one of the most common infectious diseases worldwide, with a high mortality rate, especially in patients with chronic diseases or impaired immune function. Current antifungal treatment mainly relies on antibiotics including azoles and polyenes. However, the biofilm with a three-dimensional structure formed by the extracellular matrix greatly hinders the penetration of drugs, affects the effectiveness of these drugs, and protects the internal fungi from attacks by the human immune system. In addition, long-term high-dose use of antibiotics and improper drug management will not only have adverse toxicological effects on the host, but also lead to the emergence of drug-resistant fungal strains. Therefore, the development of an antibiotic-independent therapeutic drug that can destroy biofilms is crucial for the treatment of drug-resistant fungal infections.

[0003] Reactive oxygen species (ROS) play a vital role in regulating various physiological behaviors. Immune cells kill invading pathogens through oxidative bursts during the anti-infection process. Controllable ROS generation includes singlet oxygen ( 1 O2), hydroxyl radical (·OH), superoxide anion (·O 2- ) and hydrogen peroxide (H2O2), which can cause irreversible oxidative damage to the cellular DNA or proteins of microorganisms, provide a promising strategy to address the above challenges.

[0004] Photodynamic therapy (PDT) is a minimally invasive treatment method that uses reactive oxygen species (ROS) generated by photosensitizers (PSs) under light activation to kill abnormal cells or pathogenic microorganisms. Its great potential in treating drug-resistant strains has attracted the attention of many researchers. Laser-triggered PDT based on 5-aminolevulinic acid (ALA) has demonstrated clinical efficacy in the treatment of fungal infections, however, ALA treatment is still limited by the insufficient penetration depth of 660nm light.

[0005] Nanotechnology is one of the most promising technologies in the 21st century. Various nanomaterials with controllable morphology, good biocompatibility and high loading efficiency have been used to accurately and effectively deliver a variety of therapeutic drugs, including photosensitizers, for precision treatment of diseases such as tumors and antimicrobial agents. Among them, near-infrared (NIR) light-triggered lanthanide-doped upconversion nanoparticles (UCNPs) loaded with photosensitizers have made significant progress in biological applications such as photobioimaging and energy converters.

[0006] However, the low luminescence resonance energy transfer (FRET) efficiency between UCNPs and photosensitizers limits the generation of ROS, resulting in poor therapeutic effects. Semiconductors such as titanium dioxide and carbon nitride have been reported to exhibit good photocatalytic activity, photoinduced charge carrier separation, and tunable electron-hole band structures, which provide more possibilities for promoting the energy transfer process from UCNPs to photosensitizers and thus improving the efficiency of photoinduced ROS generation. In particular, these unique semiconductors have the potential to generate ROS under ultrasound stimulation, and the physical properties of ultrasound can loosen the biofilm. Therefore, it is of great significance to construct a complex that combines photosensitizers, semiconductors and UCNPs to achieve ultrasound-synergistic photodynamic therapy to eliminate fungal biofilms. Summary of the invention

[0007] The purpose of the present invention is to provide carbon nitride modified upconversion nanoparticles loaded with ruthenium complexes, a preparation method thereof, and an application thereof in preparing a drug for treating fungal biofilm infection.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] A method for preparing carbon nitride-modified upconversion nanoparticles loaded with a ruthenium complex, the preparation process comprising:

[0010] 1) coating the lanthanide-doped upconversion nanoparticles UCNP with a double-layer silica layer, and then hydrothermally etching to obtain lanthanide-doped upconversion nanoparticles UCNP@hmSiO2 with a hollow silica outer layer;

[0011] 2) UCNP@hmSiO2 is calcined with cyanamide to react, so that cyanamide condenses in the silicon dioxide layer to form carbon nitride, and then the silicon dioxide is etched to obtain carbon nitride-modified lanthanide-doped upconversion nanoparticles UCNP@g-C3N4;

[0012] 3) Add ruthenium complex to react with UCNP@g-C3N4 to obtain carbon nitride modified upconversion nanoparticles UCNP@g-C3N4-Ru loaded with ruthenium complex.

[0013] Further, in the step 1), the outer layer of hollow silica of UCNP@hmSiO2 is obtained by hydrothermal etching after modification with hydrolysis of multiple silane precursors after phase conversion;

[0014] In the step 2), the calcination reaction of UCNP@hmSiO2 and cyanamide is carried out at a temperature of 480-550° C. in a nitrogen atmosphere, and sodium hydroxide or sodium carbonate solution is used to etch silicon dioxide;

[0015] In the step 3), the reaction temperature of the ruthenium complex and UCNP@g-C3N4 is 25-70° C., and the reaction time is 12-36 h.

[0016] Further, the detailed process of step 1) is: dissolving 100 mg of hexadecyltrimethylammonium bromide in 20 mL of deionized water, and then injecting 20 mg mL -1 UCNP 2mL cyclohexane solution, when a transparent solution is obtained, is mixed with 40mL water, 6mL ethanol, 40mg sodium salicylate and 50μL triethylamine, 60μL 1,2-bis(triethoxysilyl)ethane and 40μL tetraethyl orthosilicate are added dropwise, and the mixture is stirred overnight to obtain the product silica-coated upconversion nanoparticles UCNP@mSiO2;

[0017] UCNP@mSiO2 was dispersed in a solution containing 120 mg of hexadecyltrimethylammonium bromide, 12 mL of ethanol, 38 mL of water and 30 μL of triethylamine. After ultrasonic dispersion for 1 hour and stirring at room temperature for 1 hour, a mixture of 100 μL of tetraethyl orthosilicate and 100 μL of 1,2-bis(triethoxysilyl)ethane was quickly added to the suspension. After stirring at 25°C for 16 hours, double-layer silica-coated UCNPs were obtained. The double-layer silica-coated UCNPs were dispersed in 450 mL of water and subjected to hydrothermal etching treatment at 100°C for 12 hours. After removing the surfactant, hollow silica-coated upconversion nanoparticles UCNP@hmSiO2 were obtained.

[0018] Furthermore, the detailed process of step 2) is: UCNP@hmSiO2 is stirred in 4 mL aqueous solution containing 2 g cyanamide at room temperature for 24 hours to disperse it in the solution, centrifuged, and then heated at 5 °C·min under N2 atmosphere. -1 The mixture was heated to 550 °C for 4 h at a rate of 1.5 % and then transferred to 12 mL of Na2CO3 solution (280 mg, 0.2 mol·L -1 After reacting at 60 °C for 16 hours, carbon nitride-coated upconversion nanoparticles UCNP@g-C3N4 were obtained.

[0019] Furthermore, the detailed process of step 3) is: 5 mg of UCNP@g-C3N4 is carefully ground and dispersed in 5 mL of water, and then 0.5 mL of an ethanol solution containing 2 mg of a polypyridyl ruthenium (II) complex is added, and after vigorous stirring at 50°C for 18 h, centrifugation is performed to obtain carbon nitride upconversion nanoparticles UCNP@g-C3N4-Ru loaded with a ruthenium complex.

[0020] The invention also provides carbon nitride modified up-conversion nanoparticles loaded with ruthenium complex obtained by the preparation method.

[0021] Furthermore, the lanthanide-doped up-conversion nanoparticles are thulium-doped up-conversion nanoparticles NaYF4:Yb / Tm UCNPs based on sodium yttrium tetrafluoride, and the particle size thereof is 25-40 nm.

[0022] Furthermore, in terms of mass fraction, in the carbon nitride modified upconversion nanoparticles loaded with ruthenium complexes, lanthanide-doped upconversion nanoparticles account for 50-60%, surface g-C3N4 accounts for 20-30%, and ruthenium complexes account for 10%-20%.

[0023] The present invention also provides an application of the carbon nitride modified upconversion nanoparticles loaded with ruthenium complexes in the preparation of a drug for treating fungal biofilm infection.

[0024] Further, the fungal biofilm comprises a Candida albicans fungal biofilm.

[0025] The invention has the advantages of: proposing a semiconductor sensitized upconversion nanoparticle (UCNP@g-C3N4-Ru) loaded with a polypyridyl ruthenium (II) complex, and an ultrasound-assisted enhanced photodynamic therapy strategy thereof, for eradicating fungal biofilm-based infections. UCNP@g-C3N4-Ru is composed of thulium-doped upconversion nanoparticles (UCNP) coated with carbonitride (g-C3N4) and a photosensitizer polypyridyl ruthenium (II) complex (Ru). Among them, the polypyridyl ruthenium (II) complex shows the ability to bind DNA and generate reactive oxygen species under light. UCNP@g-C3N4-Ru can generate reactive oxygen species (ROS) under ultrasound and light irradiation, which makes the dense fungal biofilm of Candida albicans treated with UCNP@g-C3N4-Ru not only loosen effectively under ultrasound and light stimulation, but also promotes the penetration of drugs into the fungi; at the same time, the excited state of the process of generating reactive oxygen species under the excitation of ruthenium complex is caused by the charge transfer process from ruthenium metal to ligand, and the conduction band electrons of g-C3N4 in the composite particles contribute to the occurrence of this process, improving the metal-to-ligand charge transfer (MLCT) process of polypyridine ruthenium (II) complex, so that the ROS generated by UCNP@g-C3N4-Ru can kill fungi and destroy biofilm more efficiently. The present invention shows excellent antifungal biofilm effect under ultrasound combined with near-infrared light irradiation. This research on the ultrasound-assisted ROS synergistic enhancement strategy using UCNP@g-C3N4-Ru is expected to provide a new treatment method for the clinical treatment of biofilm-related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The drawings described herein are used to provide a further understanding of the present invention, constitute a part of the present application, and do not constitute an improper limitation of the present invention. In the drawings:

[0027] Figure 1 It is a schematic diagram of the synthesis process of UCNP@g-C3N4-Ru;

[0028] Figure 2 The transmission electron microscopy characterization results of UCNP, UCNP@hmSiO2, UCNP@g-C3N4, UCNP@g-C3N4-Ru, the high-resolution TEM result of UCNP@g-C3N4-Ru and the corresponding STEM elemental map;

[0029] Figure 3 are the X-ray diffraction spectra of UCNP, SiO2, g-C3N4, UCNP@g-C3N4, and UCNP@g-C3N4-Ru;

[0030] Figure 4 are the Fourier transform infrared spectra of UCNP, SiO2, g-C3N4, UCNP@hmSiO2-g-C3N4, UCNP@g-C3N4, Ru, and UCNP@g-C3N4-Ru;

[0031] Figure 5 is the X-ray photoelectron spectroscopy (XPS) graph of UCNP@g-C3N4-Ru;

[0032] Figure 6 is the UV-visible absorption spectrum of UCNP@g-C3N4-Ru and the luminescence spectrum of UCNP;

[0033] Figure 7 UCNP@g-C3N4-Ru in the near infrared (1W·cm -2 , 100 μg·mL -1 ) under singlet oxygen generation capacity result diagram;

[0034] Figure 8 This is the detection result of superoxide anion signal collected by EPR of UCNP@g-C3N4-Ru with or without ultrasonic stimulation, using DMPO as the capture agent;

[0035] Fig. 9 This is the result of the anti-Candida albicans activity test of UCNP@g-C3N4-Ru under different triggers;

[0036] Fig.10 This is the result of adding DCFH-DA to detect the Candida albicans suspension after different treatments with UCNP@g-C3N4-Ru;

[0037] Fig.11 It is the fluorescence image of active oxygen in the biofilm after different treatments of Candida albicans suspension added with UCNP@g-C3N4-Ru after adding DCFH-DA;

[0038] Fig.12It is the live and dead staining picture of Candida albicans biofilm under different treatment conditions and whether UCNP@g-C3N4-Ru was added;

[0039] Fig.13 It is a statistical chart of Candida albicans biofilm colony counts under different treatment conditions and whether UCNP@g-C3N4-Ru was added. DETAILED DESCRIPTION

[0040] The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments. The exemplary embodiments and descriptions of the present invention are used to explain the present invention, but are not intended to limit the present invention.

[0041] 1. Synthesis and characterization of UCNP@g-C3N4-Ru

[0042] like Figure 1 As shown,

[0043] 1) Coating the thulium-doped upconversion nanoparticles (UCNP) with a double layer of silicon dioxide layer, and obtaining UCNP@hmSiO2 with a space interlayer by hydrothermal etching, the specific process is as follows:

[0044] Hexadecyltrimethylammonium bromide (CTAB) (100 mg) was dissolved in 20 mL of deionized water and then injected into the UCNP containing NaYF4:Yb / Tm (20 mg mL -1 ,2mL) of cyclohexane solution. When a clear solution was obtained, the solution was transferred to a 100mL round-bottom flask and mixed with water (40mL), ethanol (6mL), sodium salicylate (40mg) and triethylamine (50μL). Then, 1,2-bis(triethoxysilyl)ethane (60μL) and tetraethyl orthosilicate (40μL) were added dropwise, and the mixture was stirred overnight. The product silica-coated upconversion nanoparticles UCNP@mSiO2 were collected by centrifugation, washed with ethanol, and dispersed in 10mL of ethanol;

[0045] UCNP@mSiO2 was dispersed in a solution containing hexadecyltrimethylammonium bromide (120 mg), ethanol (12 mL), water (38 mL) and triethylamine (30 μL). After ultrasonic dispersion for 1 hour and stirring at room temperature for 1 hour, a mixture of tetraethyl orthosilicate (100 μL) and 1,2-bis(triethoxysilyl)ethane (100 μL) was quickly added to the suspension, and after stirring at 25°C for 16 hours, double-layer silica-encapsulated UCNPs were obtained; the double-layer silica-encapsulated UCNPs were dispersed in 450 mL of water and subjected to hydrothermal etching at 100°C for 12 hours; after removing the surfactant by hydrochloric acid / ethanol extraction, hollow silica-encapsulated upconversion nanoparticles UCNP@hmSiO2 were obtained.

[0046] 2) UCNP@hmSiO2 was stirred in 4 mL aqueous solution containing 2 g cyanamide at room temperature for 24 h to disperse in the solution. The product was centrifuged and transferred to a porcelain boat. Then, the mixture was heated at 5 °C·min under N2 atmosphere. -1 The mixture was heated to 550 °C for 4 h at a rate of 1.5 % to obtain UCNP@hmSiO2@g-C3N4, which was then transferred to 12 mL of Na2CO3 solution (280 mg, 0.2 mol·L -1 ) at 60 °C for 16 h to obtain carbon nitride-coated upconversion nanoparticles UCNP@g-C3N4.

[0047] 3) UCNP@g-C3N4 (5 mg) was carefully ground and dispersed in 5 mL of water, and then 0.5 mL of ethanol solution containing 2 mg of polypyridyl ruthenium (II) complex was added. After vigorous stirring at 50°C for 18 h, the final product, carbon nitride upconversion nanoparticles loaded with ruthenium complex UCNP@g-C3N4-Ru, was collected by centrifugation.

[0048] Transmission electron microscopy characterization of UCNP, UCNP@hmSiO2, UCNP@g-C3N4, and UCNP@g-C3N4-Ru Figure 2 The first row is shown in the picture.

[0049] The high-resolution TEM results and corresponding STEM elemental maps of UCNP@g-C3N4-Ru are shown in Figure 2. Figure 2 The 2nd and 3rd rows are shown in the pictures.

[0050] X-ray diffraction spectra of UCNP, SiO2, g-C3N4, UCNP@g-C3N4, and UCNP@g-C3N4-Ru are shown in Figure 2. Figure 3 shown.

[0051] Fourier transform infrared spectra of UCNP, SiO2, g-C3N4, UCNP@hmSiO2@g-C3N4, UCNP@g-C3N4, Ru, and UCNP@g-C3N4-Ru are shown in Figure 2. Figure 4 shown.

[0052] X-ray photoelectron spectroscopy (XPS) of UCNP@g-C3N4-Ru is shown in Figure 2. Figure 5 shown.

[0053] These characterization results confirmed the successful synthesis of nanoparticles in each step of the above synthesis scheme, and finally obtained carbon nitride-modified upconversion nanoparticles loaded with ruthenium complexes (UCNP@g-C3N4-Ru).

[0054] 2. Antifungal properties of UCNP@g-C3N4-Ru

[0055] In order to detect the antifungal properties of UCNP@g-C3N4-Ru, the present invention carried out relevant experiments, and the results are as follows:

[0056] The UV-visible absorption spectrum of UCNP@g-C3N4-Ru (Ru complex) and the luminescence spectrum of UCNP are shown in Figure 6 As shown;

[0057] UCNP@g-C3N4-Ru in near infrared (1W·cm -2 , 100 μg·mL -1 The singlet oxygen generation capacity results under Figure 7 As shown;

[0058] Using DMPO as the capture agent, the superoxide anion signals collected by EPR of UCNP@g-C3N4-Ru with and without ultrasonic stimulation are shown in Figure 2. Figure 8 As shown;

[0059] Candida albicans was inoculated onto agar plates and cultured in groups according to different treatment conditions: no treatment, ultrasound, light, ultrasound + light, addition of UCNP@g-C3N4-Ru, addition of UCNP@g-C3N4-Ru + ultrasound, addition of UCNP@g-C3N4-Ru + light, and addition of UCNP@g-C3N4-Ru + ultrasound + light. Then, the anti-Candida albicans activity of UCNP@g-C3N4-Ru under different triggers was detected. The results are shown in Fig. 9 As shown in the figure, UCNP@g-C3N4-Ru is referred to as UCNR in the figure. Adding UCNP@g-C3N4-Ru+light and adding UCNP@g-C3N4-Ru+ultrasound+light have excellent anti-C. albicans activity, among which the best is the treatment of adding UCNP@g-C3N4-Ru+ultrasound+light. The colony count (1W·cm -2 , 50 μg·mL -1 );

[0060] The suspension of Candida albicans with UCNP@g-C3N4-Ru was divided into groups according to the different treatment conditions: no treatment, ultrasound, light, and ultrasound + light. DCFH-DA was added to each group to detect the Candida albicans after different treatments. Fig.10 As shown, the fluorescence of reactive oxygen species in the biofilm is Fig.11 As shown, ROS Up is the positive control;

[0061] According to the different treatment conditions of no treatment, ultrasound, light, ultrasound + light, and whether UCNP@g-C3N4-Ru was added, the DAPI-PI staining results of Candida albicans biofilm after different treatments are shown in Figure 2. Fig.12As shown in the figure, UCNP@CR represents UCNP@g-C3N4-Ru; the biofilm colony count statistics are as follows Fig.13 As shown in Figure 2, it can be seen that the addition of UCNP@g-C3N4-Ru and ultrasound + light treatment have good performance in killing Candida albicans biofilm.

[0062] The above results prove that UCNP@g-C3N4-Ru has the ability to produce ROS under ultrasound-light conditions and can kill Candida albicans under ultrasound-light synergy, especially for Candida albicans biofilm, the antibacterial effect under ultrasound-light synergy is the most significant.

[0063] The technical solutions provided by the embodiments of the present invention are introduced in detail above. Specific examples are used herein to illustrate the principles and implementation methods of the embodiments of the present invention. The description of the above embodiments is only applicable to help understand the principles of the embodiments of the present invention. At the same time, for those skilled in the art, according to the embodiments of the present invention, there will be changes in the specific implementation methods and application scopes. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A method for preparing carbon nitride modified upconversion nanoparticles loaded with ruthenium complexes, characterized in that: The preparation process includes: 1) coating the lanthanide-doped upconversion nanoparticles UCNP with a double-layer silica layer, and then hydrothermally etching to obtain lanthanide-doped upconversion nanoparticles UCNP@hmSiO2 with a hollow silica outer layer; 2) UCNP@hmSiO2 is calcined with cyanamide to react, so that cyanamide condenses in the silicon dioxide layer to form carbon nitride, and then the silicon dioxide is etched to obtain carbon nitride-modified lanthanide-doped upconversion nanoparticles UCNP@g-C3N4; 3) Add ruthenium complex to react with UCNP@g-C3N4 to obtain carbon nitride modified upconversion nanoparticles UCNP@g-C3N4-Ru loaded with ruthenium complex.

2. The method for preparing a carbon nitride modified upconversion nanoparticle loaded with a ruthenium complex according to claim 1, characterized in that: In the step 1), the outer layer of hollow silica of UCNP@hmSiO2 is obtained by hydrothermal etching after phase conversion and modification with hydrolysis of multiple silane precursors; In the step 2), the calcination reaction of UCNP@hmSiO2 and cyanamide is carried out at a temperature of 480-550° C. in a nitrogen atmosphere, and sodium hydroxide or sodium carbonate solution is used to etch silicon dioxide; In the step 3), the reaction temperature of the ruthenium complex and UCNP@g-C3N4 is 25-70° C., and the reaction time is 12-36 h.

3. The method for preparing a carbon nitride modified upconversion nanoparticle loaded with a ruthenium complex according to claim 1, characterized in that: The detailed process of step 1) is as follows: 100 mg of hexadecyltrimethylammonium bromide is dissolved in 20 mL of deionized water, and then 20 mg mL of deionized water is injected into the mixture under vigorous stirring. -1 UCNP 2mL cyclohexane solution, when a transparent solution is obtained, is mixed with 40mL water, 6mL ethanol, 40mg sodium salicylate and 50μL triethylamine, 60μL 1,2-bis(triethoxysilyl)ethane and 40μL tetraethyl orthosilicate are added dropwise, and the mixture is stirred overnight to obtain the product silica-coated upconversion nanoparticles UCNP@mSiO2; UCNP@mSiO2 was dispersed in a solution containing 120 mg of hexadecyltrimethylammonium bromide, 12 mL of ethanol, 38 mL of water and 30 μL of triethylamine. After ultrasonic dispersion for 1 hour and stirring at room temperature for 1 hour, a mixture of 100 μL of tetraethyl orthosilicate and 100 μL of 1,2-bis(triethoxysilyl)ethane was quickly added to the suspension. After stirring at 25°C for 16 hours, double-layer silica-coated UCNPs were obtained. The double-layer silica-coated UCNPs were dispersed in 450 mL of water and subjected to hydrothermal etching treatment at 100°C for 12 hours. After removing the surfactant, hollow silica-coated upconversion nanoparticles UCNP@hmSiO2 were obtained.

4. The method for preparing a carbon nitride modified upconversion nanoparticle loaded with a ruthenium complex according to claim 1, characterized in that: The detailed process of step 2) is as follows: UCNP@hmSiO2 is stirred in 4 mL aqueous solution containing 2 g cyanamide at room temperature for 24 hours to disperse in the solution, centrifuged, and then heated at 5 °C·min under N2 atmosphere. -1 The mixture was heated to 550 °C for 4 h at a rate of 1.5 % and then transferred to 12 mL of Na2CO3 solution (280 mg, 0.2 mol·L -1 After reacting at 60 °C for 16 hours, carbon nitride-coated upconversion nanoparticles UCNP@g-C3N4 were obtained.

5. The method for preparing a carbon nitride modified upconversion nanoparticle loaded with a ruthenium complex according to claim 1, characterized in that: The detailed process of step 3) is: carefully grind 5 mg of UCNP@g-C3N4 and disperse it in 5 mL of water, then add 0.5 mL of ethanol solution containing 2 mg of polypyridyl ruthenium (II) complex, stir vigorously at 50°C for 18 hours, and centrifuge to obtain carbon nitride upconversion nanoparticles UCNP@g-C3N4-Ru loaded with ruthenium complex.

6. A carbon nitride modified upconversion nanoparticle loaded with a ruthenium complex obtained by the preparation method according to any one of claims 1 to 5.

7. The method for preparing carbon nitride modified upconversion nanoparticles loaded with ruthenium complex according to claim 6, characterized in that: The lanthanide-doped up-conversion nanoparticles are thulium-doped up-conversion nanoparticles NaYF4:Yb / Tm UCNPs with sodium yttrium tetrafluoride as a matrix, and the particle size thereof is 25-40 nm.

8. The method for preparing a carbon nitride modified upconversion nanoparticle loaded with a ruthenium complex according to claim 1 or 2, characterized in that: Calculated by mass fraction, in the carbon nitride modified upconversion nanoparticles loaded with ruthenium complex, lanthanide-doped upconversion nanoparticles account for 50-60%, surface g-C3N4 accounts for 20-30%, and ruthenium complex accounts for 10%-20%.

9. Use of the carbon nitride modified upconversion nanoparticles loaded with ruthenium complex according to claim 8 in the preparation of drugs for treating fungal biofilm infections.

10. The use according to claim 6, characterized in that: The fungal biofilm comprises a Candida albicans fungal biofilm.

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