Light-operated carbon monoxide release system and preparation method thereof

Abstract

The invention provides a light-operated carbon monoxide release system and a preparation method thereof, and belongs to the technical field of nano materials. The carbon monoxide donor particles are obtained by self-assembly of components including up-conversion nanoparticles, carbon monoxide donor micromolecules and amphiphilic macromolecules. In the invention, the up-conversion nanoparticles can generate ultraviolet light and blue light under the excitation of near-infrared light, and the ultraviolet light can further excite carbon monoxide donor micromolecule 3-hydroxyflavone to release carbon monoxide and generate green light along with the carbon monoxide donor micromolecule 3-hydroxyflavone. The light-operated carbon monoxide release system disclosed by the invention realizes near-infrared laser beam mediated time-space resolution precise controlled release, and the constructed carbon monoxide release system breaks through the technical bottleneck that a traditional carbon monoxide donor lacks targeting and controllability, and shows remarkable advantages in the aspect of controlled release of a specific part in a living body; and an innovative technical platform is provided for precise gas treatment.

Description

Technical Field

[0001] The present invention relates to the technical field of nanomaterials, and particularly to a light-controlled carbon monoxide releasing system and a preparation method thereof. Background Art

[0002] Carbon monoxide (CO), as an important gaseous signaling molecule, plays a key role in physiological processes such as neural communication, vasodilation, and anti-inflammation, and shows great therapeutic potential in the fields of cardiovascular diseases, inflammation, and tumor treatment. However, its clinical application faces many challenges: firstly, as a gaseous molecule, CO has the characteristics of a short half-life and a limited diffusion distance; secondly, existing carbon monoxide donor drugs mainly rely on passive transport, are easily non-specifically adsorbed or cleared by tissues, resulting in low drug utilization rate at the lesion site; in addition, these donor drugs usually release CO spontaneously, which may cause systemic side effects and limit their clinical application.

[0003] To solve these problems, researchers have developed a variety of stimulus-responsive carbon monoxide delivery systems, including microparticles that respond to endogenous stimuli (such as pH, reactive oxygen species, enzymes) and exogenous stimuli (such as magnetic fields, ultrasound, X-rays). However, these systems still have defects such as lack of targeting, imprecise time and space control, and imprecise control routes, and it is difficult to achieve precise spatio-temporal controlled delivery. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a light-controlled carbon monoxide releasing system and a preparation method thereof. The light-controlled carbon monoxide releasing system provided by the present invention has good targeting and controllability, and can achieve spatio-temporal resolved precise controlled release mediated by a near-infrared laser beam.

[0005] To achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0006] The present invention provides a carbon monoxide donor microparticle, which is self-assembled from components including upconversion nanoparticles, a carbon monoxide donor small molecule, and an amphiphilic polymer;

[0007] The upconversion nanoparticles are Tm 3+ -doped NaYbF4 nanoparticles;

[0008] The carbon monoxide donor small molecule is 3-hydroxyflavone.

[0009] Preferably, the amphiphilic polymer includes DSPE-PEG-NH2; the relative molecular weight of the DSPE-PEG-NH2 is 200-50000.

[0010] Preferably, the doping amount of Tm 3+ in the upconversion nanoparticles is 0.1-5 wt%.

[0011] The particle size of the upconversion nanoparticles is 40 to 60 nm.

[0012] Preferably, the mass ratio of the upconversion nanoparticles, the carbon monoxide donor small molecule and the amphiphilic polymer is 50 to 100:10:1;

[0013] The particle size of the carbon monoxide donor microparticles is 1.0 to 1.4 μm.

[0014] The present invention provides a method for preparing the above-mentioned carbon monoxide donor microparticles, comprising the following steps:

[0015] Ultrasonically mix the upconversion nanoparticles, the carbon monoxide donor small molecule, the amphiphilic polymer and the organic solvent to obtain a mixed solution;

[0016] Remove the organic solvent in the mixed solution, mix the remaining substance with a buffer solution, and perform dialysis to obtain the carbon monoxide donor microparticles.

[0017] Preferably, the power of the ultrasonic mixing is 20 to 50 kHz, and the time is 3 to 5 min;

[0018] The cut-off molecular weight of the dialysis is 100 kDa.

[0019] The present invention provides a light-controlled carbon monoxide release system, comprising a trigger and the above-mentioned carbon monoxide donor microparticles;

[0020] The trigger is a near-infrared laser beam.

[0021] Preferably, the wavelength of the near-infrared laser beam is 700 to 1700 nm.

[0022] The present invention provides a method for preparing the above-mentioned light-controlled carbon monoxide release system, comprising the following steps:

[0023] Assemble the near-infrared laser beam and the carbon monoxide donor microparticles to obtain a light-controlled carbon monoxide release system;

[0024] The assembly method is scanning optical tweezers assembly.

[0025] The present invention provides the application of the above-mentioned light-controlled carbon monoxide release system in the preparation of anti-inflammatory drugs, cardiovascular disease drugs or over-immune drugs.

[0026] The present invention provides a carbon monoxide donor microparticle, which is self-assembled from components including upconversion nanoparticles, a carbon monoxide donor small molecule and an amphiphilic polymer; the upconversion nanoparticles are Tm 3+Doped NaYbF4 nanoparticles; the carbon monoxide donor small molecule is 3-hydroxyflavone. In the present invention, the upconversion nanoparticles serve as the light-responsive core, the carbon monoxide donor molecules serve as the gas release source, and the amphiphilic polymer provides a stable carrier structure. In the present invention, the upconversion nanoparticles are doped with Tm 3+ Doped NaYbF4 nanoparticles, which have a refractive index as high as 1.47, significantly higher than the refractive index of the dispersion system in the use environment, and are thus easily captured by a near-infrared laser beam and optically manipulated. Under the excitation of near-infrared light, the upconversion nanoparticles can generate ultraviolet light and blue light, and the ultraviolet light can further excite the carbon monoxide donor small molecule 3-hydroxyflavone to release carbon monoxide, accompanied by the generation of green light. It is worth noting that when 3-hydroxyflavone releases carbon monoxide, the intensity of its green fluorescence will correspondingly decrease, and this phenomenon can be used as an effective indicator of carbon monoxide release. In addition, the amphiphilic polymer in the carbon monoxide donor particles plays a key role in the structure of the carbon monoxide donor particles, and it realizes the effective connection between the upconversion nanoparticles and the carbon monoxide donor small molecules.

[0027] The present invention provides a light-controlled carbon monoxide release system, comprising a trigger and the above-mentioned carbon monoxide donor particles; the trigger is a near-infrared laser beam. The core of the light-controlled carbon monoxide release system of the present invention lies in using a near-infrared laser to simultaneously achieve the positioning and manipulation of the carrier particles and the controllable release of gas molecules. By adjusting the laser power (10-1000 mW) and the irradiation time (1-120 s), the release rate of carbon monoxide can be precisely controlled. The present invention realizes the spatio-temporal resolution and precise controlled release mediated by a near-infrared laser beam through precise regulation of the nano-composite structure. The constructed carbon monoxide release system breaks through the technical bottlenecks of the traditional carbon monoxide donors lacking targeting and controllability, and shows significant advantages in the controllable release at specific sites in vivo, providing an innovative technical platform for precise gas therapy. The present invention provides technical support for the targeted separation of diseased cells and has important application value in the field of precision medicine for cardiovascular diseases such as thrombosis and anti-inflammatory, especially showing significant advantages in autoimmune hemolytic anemia, atherosclerotic plaque ablation, etc. In addition, the system also has good biocompatibility and biodegradability, providing a feasibility guarantee for clinical transformation. Description of the Drawings

[0028] Figure 1 Schematic diagram of the structure of the carbon monoxide donor particles and mechanism diagram of carbon monoxide release;

[0029] Figure 2 Microscopic structure diagram of the carbon monoxide donor particles;

[0030] Figure 3 Hydration kinetic diameter diagram of the carbon monoxide donor particles;

[0031] Figure 4 Fluorescence image excited by 1064 nm laser absorbed by carbon monoxide donor particles;

[0032] Figure 5 Green fluorescence spectrum excited by blue-violet light emitted by upconversion received by carbon monoxide donor particles;

[0033] Figure 6 Imaging of precise movement of the light-controlled carbon monoxide release system;

[0034] Figure 7 Effect diagram of platelet deactivation and leukocyte inactivation induced and activated by the light-controlled carbon monoxide release system;

[0035] Figure 8 Effect diagram of the treatment of zebrafish leukocyte hemolysis by the light-controlled carbon monoxide release system. Specific implementation mode

[0036] The present invention provides a carbon monoxide donor particle, which is self-assembled from components including upconversion nanoparticles, carbon monoxide donor small molecules and amphiphilic polymers;

[0037] The upconversion nanoparticles are Tm 3+ -doped NaYbF4 nanoparticles;

[0038] The carbon monoxide donor small molecule is 3-hydroxyflavone.

[0039] In the present invention, the core of the carbon monoxide donor particle is preferably an upconversion nanoparticle, and the amphiphilic polymer connects the upconversion nanoparticle core and the carbon monoxide donor small molecule.

[0040] In the present invention, the particle size of the upconversion nanoparticles is preferably 40-60 nm, more preferably 50 nm. In the present invention, the Tm 3+ -doped NaYbF4 nanoparticles, the doping amount of Tm 3+ is preferably 0.1-5 wt%, more preferably 0.5-4 wt%, and specifically can be 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt% or 5 wt%.

[0041] In the present invention, the preparation method of the Tm 3+ -doped NaYbF4 nanoparticles preferably includes the following steps:

[0042] Mix soluble ytterbium salt, soluble thulium salt with water, and add oleic acid and high-boiling solvent to the obtained aqueous solution to obtain a mixed solution;

[0043] Add NH4F and sodium oleate to the mixed solution, perform gradient heat treatment, add an alcohol solvent for precipitation to obtain Tm 3+ doped NaYbF4 nanoparticles.

[0044] In the present invention, the soluble ytterbium salt is preferably YbCl3, and the soluble thulium salt is preferably TmCl3; the molar ratio of the soluble ytterbium salt to the soluble thulium salt is preferably 95-99.9:0.1-5. In the present invention, in the aqueous solution, the total molar concentration of the soluble ytterbium salt and the soluble thulium salt is preferably 1-1.5 mol / L, more preferably 1.2-1.4 mol / L.

[0045] In the present invention, the high-boiling solvent is preferably 1-octadecene; in the present invention, the volume ratio of oleic acid to the high-boiling solvent is preferably 1:1; the volume ratio of the aqueous solution to oleic acid is preferably 1:10-1:12, more preferably 1:11. In the present invention, the function of oleic acid is a surfactant.

[0046] After obtaining the mixed solution, the present invention preferably stirs and heats the obtained mixed solution to remove moisture. In the present invention, the stirring is preferably carried out in a nitrogen atmosphere; the heating temperature is preferably 160-165 °C, and the time is preferably 1-1.2 h. After the heating is completed, the present invention preferably cools the obtained mixed solution to 50 °C and then adds NH4F and sodium oleate.

[0047] In the present invention, the mass ratio of the total molar amount of the soluble ytterbium salt and the soluble thulium salt to NH4F and sodium oleate is preferably 1-1.1 mmol:0.34 g:2.03 g.

[0048] In the present invention, the gradient heat treatment preferably includes: first heat preservation and degassing at 110-120 °C in sequence, second heat preservation at 290-295 °C, and finally cooling to room temperature.

[0049] In the present invention, the heating rate of the gradient heat treatment is preferably 1-5 °C / min; in the present invention, the time of the first heat preservation is preferably 30 min, and the time of degassing is preferably 30-32 min. The time of the second heat preservation is preferably 50 min.

[0050] In the present invention, the alcohol solvent is preferably ethanol and / or propanol.

[0051] After adding the alcohol solvent for precipitation, the present invention preferably centrifuges the obtained precipitation system, discards the supernatant to obtain dense Tm 3+ doped NaYbF4 nanoparticles. In the present invention, the centrifugation rate is preferably 15000-16000 rpm, and the time is preferably 10-12 min.

[0052] to obtain the Tm 3+ After the doped NaYbF4 nanoparticles, the present invention preferably performs the following operations on the obtained Tm 3+ The doped NaYbF4 nanoparticles are washed, and the washed nanoparticles are stored in cyclohexane for preservation. In the present invention, the reagents used for washing are preferably cyclohexane and ethanol, and the volume ratio of cyclohexane to ethanol is preferably 1:1; the number of washing times is preferably 3 times.

[0053] In the present invention, the amphiphilic polymer is preferably DSPE-PEG-NH2, and its Chinese name is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (polyethylene glycol) amine; the relative molecular weight of DSPE-PEG-NH2 is preferably 200 - 50000, more preferably 500 - 40000, and further preferably 10000 - 30000.

[0054] In the present invention, the mass ratio of the amphiphilic polymer, upconversion nanoparticles, and carbon monoxide donor small molecule is preferably 50 - 100:10:1, more preferably 60 - 80:10:1.

[0055] In the present invention, the particle size of the carbon monoxide donor microparticles is preferably 1.0 - 1.4 μm, more preferably 1.2 μm.

[0056] The present invention provides a method for preparing the above carbon monoxide donor microparticles, comprising the following steps:

[0057] The upconversion nanoparticles, carbon monoxide donor small molecule, amphiphilic polymer, and organic solvent are ultrasonically mixed to obtain a mixed solution;

[0058] The organic solvent in the mixed solution is removed, and the remaining substance is mixed with a buffer solution and dialyzed to obtain carbon monoxide donor microparticles.

[0059] In the present invention, the upconversion nanoparticles, carbon monoxide donor small molecule, amphiphilic polymer, and organic solvent are ultrasonically mixed to obtain a mixed solution. In the present invention, the upconversion nanoparticles are preferably provided in the form of a dispersion, and the solvent of the upconversion nanoparticle dispersion is preferably an organic solvent, more preferably cyclohexane. In the present invention, the concentration of the upconversion nanoparticle dispersion is preferably 10 - 12 mg / mL, specifically 10 mg / mL, 11 mg / mL, or 12 mg / mL; the carbon monoxide donor small molecule is preferably provided in the form of an acetone dispersion, and the concentration of the carbon monoxide donor small molecule acetone dispersion is preferably 5 mg / mL.

[0060] In the present invention, the organic solvent is preferably dichloromethane or ethanol. There is no special requirement for the amount of the organic solvent in the present invention, and it only needs to satisfy the dispersion of the raw materials. As a specific embodiment of the present invention, the mass ratio of the upconversion nanoparticles to the volume of the organic solvent is preferably 0.5 - 1 mg:1 mL.

[0061] In the present invention, the power of the ultrasonic mixing is preferably 20 - 50 kHz, more preferably 30 - 40 kHz, and the time is preferably 3 - 5 min, more preferably 4 min.

[0062] After obtaining the mixed solution, the present invention removes the organic solvent in the mixed solution, mixes the remaining substance with a buffer solution, and performs dialysis to obtain carbon monoxide donor microparticles. In the present invention, the method for removing the organic solvent is preferably natural drying or nitrogen blowing.

[0063] In the present invention, the buffer solution is preferably PBS buffer solution; the method for mixing the remaining substance with the buffer solution is preferably ultrasonic mixing to obtain a uniformly dispersed microparticle solution. In the present invention, the power of the ultrasonic mixing is preferably 20 - 50 kHz, more preferably 30 - 40 kHz, and the time is preferably 3 - 5 min, more preferably 4 min.

[0064] In the present invention, the cut-off molecular weight of the dialysis is preferably 100 kDa; the present invention preferably uses an ultrafiltration centrifugal tube for the dialysis. In the present invention, the dialysis is preferably carried out under centrifugation conditions, and the rotation speed of the centrifugation is preferably 3000 - 4000 rpm, more preferably 3500 - 4000 rpm, and the time is preferably 3 - 10 min, more preferably 4 - 5 min.

[0065] After the dialysis, the present invention preferably filters the obtained dialysis product, and the present invention preferably uses a polyethersulfone filter membrane with a pore size of 0.22 μm for the filtration.

[0066] The present invention provides a light-controlled carbon monoxide release system, including a trigger and the above-mentioned carbon monoxide donor microparticles;

[0067] The trigger is a near-infrared laser beam.

[0068] In the present invention, the wavelength of the near-infrared laser beam is preferably 700 - 1700 nm, more preferably 1064 - 1500 nm. In the present invention, the laser power of the infrared laser beam is preferably 10 - 1000 mW, more preferably 100 - 800 mW, and further preferably 200 - 500 mW.

[0069] The present invention provides a preparation method of the above-mentioned light-controlled carbon monoxide release system, including the following steps:

[0070] Assemble a near-infrared laser beam with carbon monoxide donor microparticles to obtain a light-controlled carbon monoxide release system;

[0071] The assembly method is optical tweezers scanning assembly. The spot diameter of the optical tweezers scanning assembly is preferably 1000 nm, the scanning frequency is preferably 100 kHz, and the laser intensity is preferably 10 - 1000 mW.

[0072] In the present invention, the assembly is preferably carried out in an aqueous dispersion system.

[0073] The present invention provides the application of the above light-controlled carbon monoxide release system in the preparation of anti-inflammatory drugs, cardiovascular disease drugs or over-immune drugs. In the present invention, the cardiovascular diseases preferably include immune hemolysis, thrombosis or atherosclerosis.

[0074] As a specific embodiment of the present invention, the structural schematic diagram of the carbon monoxide donor microparticles and the mechanism diagram of carbon monoxide release are as shown in Figure 1 shown. Figure 1 In the figure, UCNP represents upconversion nanoparticles, DSPE-PEG-2K represents an amphiphilic polymer of DSPE-PEG-NH2 with a molecular weight of 2000, and CORM represents a carbon monoxide donor small molecule.

[0075] The following combines examples to detail the light-controlled carbon monoxide release system provided by the present invention and its preparation method, but they cannot be understood as limiting the protection scope of the present invention.

[0076] Example 1

[0077] (1) Add an aqueous solution mixture of 1 mmol (1 mL, 1 M) of the corresponding rare earth chloride (YbCl3: 0.92 mmol, TmCl3: 0.08 mmol) to a 100 mL flask containing 10 mL of oleic acid and 10 mL of 1-octadecene. Stir the mixture under a nitrogen atmosphere and heat to 160 °C for 1 hour to remove moisture. Then cool the mixture to 50 °C, quickly add 0.34 g of NH4F and 2.03 g of sodium oleate. Heat the solution to 110 - 120 °C for 30 minutes and degas for 30 minutes, then heat the solution to 290 °C and hold for 50 minutes, and then cool to room temperature. Precipitate the prepared nanoparticles by adding 20 mL of ethanol, and centrifuge the resulting mixture (15000 rpm, 10 minutes) into compact particles, discarding the supernatant. Collect the product and wash it three times with cyclohexane and ethanol (40 mL, 1:1, v / v) to obtain upconversion nanoparticles with a particle size of 40 - 60 nm. Store the upconversion nanoparticles in 10 mL of cyclohexane for shell coating.

[0078] (2) Preparation of upconversion nanoparticle solution:

[0079] Mix 0.1 g of the above-mentioned upconversion nanoparticles with 10 mL of cyclohexane uniformly to obtain a solution of upconversion nanoparticles with a concentration of 10 mg / mL.

[0080] (3) Preparation of carbon monoxide donor microparticles:

[0081] Mix 50 μL of the upconversion nanoparticle solution with a concentration of 10 mg / mL, 5 mg of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (polyethylene glycol) amine (molecular weight 2k), 10 μL of the acetone solution of 3-hydroxyflavone with a concentration of 5 mg / mL with 1 mL of dichloromethane, and perform ultrasonic dispersion for 3 minutes to obtain a uniform mixture. Subsequently, blow dry the dichloromethane, n-hexane, and acetone in the mixture using a nitrogen stream to form a dry solid film. Add 1 mL of PBS buffer to the solution containing the solid film, and perform ultrasonic treatment at a power of 20 - 50 kHz for 3 minutes to obtain a uniformly dispersed microparticle solution. Next, use an ultrafiltration centrifugal tube with a cut-off molecular weight of 100 kDa to centrifuge the microparticle solution at a speed of 4000 rpm for 10 minutes. After removing the supernatant, filter the centrifuged crude product with a polyethersulfone membrane with a pore size of 0.22 μm to finally obtain a carbon monoxide donor microparticle solution with uniform particle size.

[0082] The micrograph of the obtained carbon monoxide donor microparticles is as shown in Figure 2 Figure [Figure number not provided in the original]. It can be seen that the obtained carbon monoxide donor microparticles are spherical.

[0083] The hydrated kinetic diameter graph of the obtained carbon monoxide donor microparticles is as shown in Figure 3 Figure [Figure number not provided in the original]. It can be seen that the particle size of the obtained carbon monoxide donor microparticles is about 1.2 μm.

[0084] The fluorescence graph of the obtained carbon monoxide donor microparticles excited after absorbing 1064 nm near-infrared laser is as shown in Figure 4 Figure [Figure number not provided in the original], Figure 4 in which the red line is the fluorescence spectrum excited by the upconversion nanoparticles after absorbing 1064 nm near-infrared laser, and the black line is the absorption spectrum of the carbon monoxide donor. It can be seen from Figure 4 Figure [Figure number not provided in the original] that energy transfer has occurred successfully between the upconversion nanoparticles and the CO donor.

[0085] The green fluorescence spectrum graph of the obtained carbon monoxide donor microparticles excited after receiving the blue-violet light emitted by the upconversion is as shown in Figure 5 Figure [Figure number not provided in the original]. It can be seen from Figure 5 Figure [Figure number not provided in the original] that CO has been successfully released and emits green light.

[0086] Example 2

[0087] The carbon monoxide donor particle solution prepared in Example 1 was diluted with PBS buffer to obtain a particle solution with a concentration of 1 mg / mL. 100 μL of the diluted particle solution was dropped onto a glass slide, and the glass slide was placed on the three-dimensional displacement platform of a Scanning Optical Tweezers system. Subsequently, the particles on the glass slide were irradiated with a near-infrared laser beam with a wavelength of 1064 nm (power: 100 mW, time: 10 s). The particles in the solution were captured and precisely manipulated by optical tweezers technology (spot diameter: 1000 nm, scanning frequency: 100 kHz). While inducing the release of carbon monoxide, the movement trajectories of the particles were navigated in real time.

[0088] Figure 6 Schematic diagrams of the movement trajectories of multiple typical light-controlled carbon monoxide release systems in Example 1 are shown. By Figure 6 analysis, it can be seen that the light-controlled carbon monoxide release system provided by the present invention can achieve precise regulation of the movement trajectories of carbon monoxide donor particles through optical regulation means. Its spatial positioning accuracy can reach the micron level, and the response time is in the millisecond range.

[0089] Application Example 1

[0090] The carbon monoxide donor particle solution prepared in Example 1 (initial concentration: 10 mg / mL) was serially diluted with sterile PBS buffer to a working concentration of 0.1 mg / mL and then inoculated into a pre-cultured cell co-incubation system. The Scanning Optical Tweezers system was used in the experiment. In an experimental device equipped with a three-dimensional nano-positioning platform and a confocal imaging module, a 1064 nm near-infrared laser (power: 100 mW, time: 10 s) was applied to achieve optical capture and subcellular-level precise positioning of the particles. Figure 7 It is a diagram showing the deactivation of platelets and inactivation of white blood cells induced and activated by the light-controlled carbon monoxide release system. Figure 7 In the figure, at 1 s, the particles were manipulated to the platelets and white blood cells, and CO was released. Subsequently, the pseudopods of the platelets retracted, and the antennae of the white blood cells retracted. Morphological analysis showed that after CO intervention, the pseudopods of the platelets retracted and the membranes of the white blood cells shrank, confirming that the light-controlled system can achieve spatiotemporally controllable CO delivery, effectively reverse the platelet activation cascade reaction, and regulate the inflammatory response of white blood cells.

[0091] Application Example 2

[0092] The carbon monoxide donor particle solution prepared in Example 1 was diluted with phosphate buffer to obtain a particle solution with a concentration of 1 mg / mL. Through a microinjection device, 10 nL of the diluted particle solution was injected into the venous blood vessels of the thrombus zebrafish. Subsequently, the particles were precisely manipulated to the thrombus lesion site using a 1064 nm laser trapping technique (power 100 mW, time 10 s). As Figure 8 shown, at 1 s, the optical tweezers manipulated the particles to reach the leukocytes, releasing CO. After 64 s, the leukocytes were inactivated and the red blood cells and leukocytes were separated. This shows that the light-controlled carbon monoxide release system can release carbon monoxide at the lesion site and effectively control leukocyte activation. Then, the red blood cells attacked by the leukocytes were removed using the optical tweezers technique, thus achieving the treatment of leukocytic hemolysis. This process demonstrates the precise manipulation and treatment potential of the system.

[0093] The above are only the preferred embodiments of the present invention. It should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A carbon monoxide donor particle, characterized in that, Self-assembled from components including upconversion nanoparticles, carbon monoxide donor small molecules, and amphiphilic polymers; The upconversion nanoparticles are Tm 3+ -doped NaYbF4 nanoparticles; The carbon monoxide donor small molecule is 3-hydroxyflavone.

2. The carbon monoxide donor particles according to claim 1, wherein The amphiphilic polymer includes DSPE-PEG-NH2; the relative molecular weight of DSPE-PEG-NH2 is 200 to 50,000.

3. The carbon monoxide donor particles according to claim 1, characterized in that, The doping amount of Tm in the upconversion nanoparticles 3+ is 0.1 to 5 wt%; The particle size of the upconversion nanoparticles is 40 to 60 nm.

4. The carbon monoxide donor particles according to claim 1 or 2, characterized in that, The mass ratio of the upconversion nanoparticles, carbon monoxide donor small molecules, and amphiphilic polymers is 50 to 100:10:1; The particle size of the carbon monoxide donor microparticles is 1.0 to 1.4 μm.

5. The preparation method of the carbon monoxide donor particles according to any one of claims 1 to 4, characterized in that, Comprising the following steps: Ultrasonically mix the upconversion nanoparticles, carbon monoxide donor small molecules, amphiphilic polymers, and organic solvent to obtain a mixed solution; Remove the organic solvent from the mixed solution, mix the remaining substances with a buffer solution, and perform dialysis to obtain carbon monoxide donor microparticles.

6. The preparation method according to claim 5, characterized in that, The power of the ultrasonic mixing is 20 to 50 kHz, and the time is 3 to 5 min; The cut-off molecular weight of the dialysis is 100 kDa.

7. A light-controlled carbon monoxide release system, comprising a trigger and the carbon monoxide donor microparticles described in any one of claims 1 to 4 or the carbon monoxide donor microparticles prepared by the preparation method described in claim 5 or 6; The trigger is a near-infrared laser beam.

8. The photo-controlled carbon monoxide releasing system according to claim 7, wherein, The wavelength of the near-infrared laser beam is 700 to 1700 nm.

9. The preparation method of the light-controlled carbon monoxide releasing system according to claim 7 or 8, characterized in that, Comprising the following steps: Assemble the near-infrared laser beam with the carbon monoxide donor microparticles to obtain a light-controlled carbon monoxide release system; The assembly method is scanning optical tweezers assembly.

10. Use of the light-controlled carbon monoxide release system described in claim 7 or 8 or the light-controlled carbon monoxide release system prepared by the preparation method described in claim 9 in the preparation of anti-inflammatory drugs, cardiovascular disease drugs, or over-immune drugs.

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