Injectable near-infrared light response photoelectric nanoparticle hydrogel and preparation method thereof

Abstract

The invention discloses injectable near-infrared light response photoelectric nanoparticle hydrogel and a preparation method thereof, and belongs to the technical field of medical materials.The preparation method comprises the steps that a photoelectric nanoparticle aqueous dispersion containing a surfactant and an organic photoelectric semiconductor is added into a mixed solution of a NaOH aqueous solution and an HBSS solution, then rat tail collagen is added, the mixture is stirred to be uniform, and the injectable near-infrared light response photoelectric nanoparticle hydrogel is obtained. And then uniformly mixing with a PBS (Phosphate Buffer Solution) for crosslinking. By adjusting a donor-acceptor material system and a phase separation scale, the particles realize efficient exciton dissociation and photon-generated carrier generation in a brain tissue optical window (approximately equal to 850 nm). According to the invention, rat tail collagen is used as a biocompatible matrix, near-infrared response BHJ photoelectric nanoparticles are introduced into a gel forming process, and injectable photoelectric-collagen composite gel with fluidity, rapid gel forming and uniformly distributed photoelectric functions is constructed and can be used as a three-dimensional hydrogel material system with near-infrared light triggered electric response characteristics. And a material basis is provided for related biomedical engineering application.

Description

Technical Field

[0001] This invention belongs to the field of medical-engineering interdisciplinary technology, specifically relating to an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel and its preparation method. Background Technology

[0002] Central nervous system injuries (such as stroke and spinal cord injury) often lead to neuronal death, axonal breakage, and loss of synaptic connections, making it one of the most challenging major disease types in clinical treatment. To improve the microenvironment of the injured area and promote neural function reconstruction, researchers have proposed simulating the electrophysiological characteristics of neural tissue development by constructing three-dimensional scaffold materials and introducing electrical stimulation signals. Neural stem cell transplantation is considered a promising research direction, but its application is limited by factors such as the lack of stable support structures in the transplantation microenvironment and limitations in electrophysiological stimulation methods.

[0003] To address these issues, existing research has attempted to replace traditional metal electrodes with flexible materials such as conductive hydrogels to achieve adhesive electrical stimulation in soft tissues. However, current conductive hydrogel systems typically rely on external wire connections, posing risks of trauma, infection, and insufficient long-term stability in vivo. Furthermore, while some hydrogel materials based on natural polymers possess good biocompatibility, they lack the ability to generate remote, spatiotemporally controllable electrical signals. Therefore, achieving wireless and controllable electrical response while maintaining material injectability and biocompatibility remains a critical technical challenge in this field. Summary of the Invention

[0004] To address the problem that existing hydrogel materials cannot simultaneously achieve wireless and controllable electroresponsiveness while satisfying injectability and biocompatibility, the present invention aims to provide an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel and its preparation method. The hydrogel prepared by this method has excellent injectable gelation characteristics and near-infrared light-excited photoelectric response performance. It can form a stable three-dimensional structure under physiological conditions and realize the generation of electrical signals triggered by near-infrared light, thereby providing a technical means for constructing a three-dimensional hydrogel material system with electrophysiological regulation capabilities.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel includes the following steps: A hydrogel of photoelectric nanoparticles containing surfactants and organic photoelectric semiconductors, along with rat tail collagen, was added to a mixed solution of NaOH aqueous solution and HBSS solution to obtain a hydrogel of photoelectric nanoparticles. The photoelectric nanoparticle hydrogel was mixed with an equal volume of PBS buffer to obtain a hydrogel dilution. The hydrogel dilution was then crosslinked to obtain an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel.

[0006] Furthermore, the aqueous dispersion of optoelectronic nanoparticles containing surfactants and organic optoelectronic semiconductors is prepared through the following process: Add a surfactant to water, dissolve it, filter it, and obtain the aqueous phase. An organic photoelectric semiconductor was dissolved in chloroform to obtain an oil phase; wherein the organic photoelectric semiconductor was a mixture of P-type and N-type semiconductors. The oil phase was added to the aqueous phase, and the mixture was subjected to ultrasound and heating to obtain an aqueous dispersion of photoelectric nanoparticles.

[0007] Furthermore, the surfactant is a phospholipid surfactant.

[0008] Furthermore, the phospholipid surfactants are egg yolk lecithin, egg yolk phosphatidylglycerol, or sphingomyelin.

[0009] Furthermore, the concentration of the aqueous phase is 1 mg / mL, and the concentration of the oil phase is 15 mg / mL; the volume ratio of the aqueous phase to the oil phase is (8~12):1.

[0010] Furthermore, the P-type semiconductors are designated as PM6, P3HT, D18, or PTQ-10, while the N-type semiconductors are designated as Y6, PCBM, or L8-BO.

[0011] Furthermore, the mass ratio of P-type semiconductors to N-type semiconductors is 1:(0.8~1.2).

[0012] Furthermore, the pH of the optoelectronic nanoparticle hydrogel is 7-7.4; the concentration of the hydrogel diluent is 2 mg / mL.

[0013] Furthermore, the cross-linking temperature was 37°C and the time was 10 min.

[0014] An injectable near-infrared light-responsive optoelectronic nanoparticle hydrogel.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: In this invention, P-type semiconductors serve as donor materials and N-type semiconductors as acceptor materials. By adjusting the donor-acceptor material system and phase separation scale, particles achieve efficient exciton dissociation and photogenerated carrier generation within the optical window (≈850 nm) of brain tissue. This invention uses rat tail collagen as a biocompatible matrix and introduces near-infrared responsive BHJ optoelectronic nanoparticles into the gelation process to construct an injectable optoelectronic-collagen composite gel that combines fluidity, rapid gelation, and uniform distribution of optoelectronic functions. This overcomes the problem that traditional composite hydrogels struggle to simultaneously achieve injectability, rapid gelation, and spatial uniformity of optoelectronic signals, leading to difficulties in forming a stable and controllable electrophysiological microenvironment in vivo. This invention is the first to embed near-infrared light-excited organic bulk heterojunctions into rat tail collagen, successfully preparing optoelectronic nanoparticle collagen-based hydrogels. This provides material support and an electrical signal source for constructing three-dimensional hydrogel microenvironment structures with near-infrared light-triggered electrical response characteristics. This invention differs significantly from existing technologies in terms of material type, excitation wavelength, molding method, and functional coupling, overcoming the bottlenecks of "injectable hydrogels cannot generate electrical stimulation" and "rigid electrical stimulation devices are not injectable." Addressing the limitations of existing neural repair materials, which rely on external rigid electrodes or mechanical / magnetic / ultrasonic stimulation, resulting in high invasiveness, limited action area, and poor compatibility with soft tissue, this invention innovatively proposes a construction strategy of "injectable three-dimensional organic optoelectronic microenvironment." Near-infrared light-responsive organic bulk heterojunction nanoparticles are integrated into a temperature-sensitive injectable hydrogel network to form a novel photoresponsive composite scaffold material. Compared with existing technologies, this invention achieves three major breakthroughs: First, in terms of the mechanism of action, since near-infrared light can penetrate human tissue and skull, it utilizes near-infrared light to wirelessly and precisely generate electrophysiological signals in situ under wet conditions, overcoming the drawbacks of traditional wire-dependent electrical stimulation and the inability of light to penetrate tissues. Second, in terms of structural design, it achieves a uniform and robust distribution of photoelectric active units in the three-dimensional scaffold, forming a three-dimensional microenvironment structure with tunable electroresponsive characteristics, superior to simple two-dimensional surface modification or physical mixing materials. Third, in terms of functional integration, it simultaneously achieves technical synergy in the material system's three-dimensional scaffold construction, minimally invasive injection molding, and phototriggered electroresponsive functional integration. Therefore, this invention constitutes a substantial innovation distinct from existing technologies in terms of core materials, composite structure, and functional realization, providing a new technical solution for developing a three-dimensional hydrogel material platform with wireless phototriggered electroresponsive characteristics.

[0016] Furthermore, photoelectric nanoparticles were prepared using an emulsification-evaporation method, and the dispersibility and interfacial stability of the particles in the physiological environment were improved by surfactants, forming the first stable BHJ photoelectric nanosystem for in vivo applications. This overcomes the problems of traditional organic photoelectric materials being prone to hydration, interfacial energy level drift, and enhanced charge recombination in the physiological environment, resulting in low photocurrent conversion efficiency and restricting their application in in vivo electrophysiological regulation.

[0017] Furthermore, this invention uses natural high-molecular-weight rat tail collagen as the matrix material of the hydrogel. Utilizing naturally derived collagen to autonomously assemble a cross-linked network provides excellent biocompatibility and a cell growth scaffold, and offers material support for related biomedical engineering research. Using collagen as a biocompatible matrix, near-infrared responsive BHJ optoelectronic nanoparticles are introduced into the gelation process to construct an injectable optoelectronic-collagen composite gel that combines fluidity, rapid gelation, and uniform distribution of optoelectronic functions. It cross-links at 37°C (human body temperature), remains fluid at low temperatures, possesses injectable properties, and provides support for subsequent biological experiments. Attached Figure Description

[0018] Figure 1 The molecular formula, particle size distribution, UV absorption map, and cryo-electron microscopy image of the photoelectric nanoparticles prepared in Example 1 of this invention are shown below; where a is the particle size distribution, b is the UV absorption map, c is the cryo-electron microscopy image of the nanoparticles, and d is the molecular formula of PM6 and Y6. Figure 2 The images show the SEM and UV absorption spectra of the photoelectric nanoparticle hydrogel prepared in Example 1 of this invention; where a is the SEM image and b is the UV absorption spectra. Figure 3 The diagram shows the injectability of the optoelectronic nanoparticle hydrogel prepared in Example 1 of this invention. In the diagram, a shows the injectability at 4°C, and b shows the solid state of the hydrogel after cross-linking at 37°C. Figure 4 The images show the photocurrent and near-infrared photocurrent response of the photoelectric nanoparticle hydrogel prepared in Example 1 of this invention, measured by patch clamp. In the image, a represents the photocurrent of the photoelectric nanoparticle hydrogel after 1 second of 564 nm laser irradiation; b represents the photocurrent of the photoelectric nanoparticle hydrogel measured under 564 nm laser light with a cycle of 500 ms irradiation followed by 500 ms off; and c represents the photocurrent of the PM6:Y6 pure film measured under 850 nm infrared light using an electrochemical workstation with a cycle of 500 ms irradiation followed by 500 ms off. Detailed Implementation

[0019] The present invention will now be described in detail with reference to specific embodiments. However, it should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. Improvements and adjustments made by those skilled in the art based on the present invention in practical applications still fall within the scope of protection of the present invention.

[0020] Targeting tissue environments rich in water and ions, this study utilizes donor-acceptor molecular design and surface chemical regulation to construct near-infrared responsive, long-lived bulk heterojunction (BHJ) optoelectronic nanoparticles, achieving stable photoelectric conversion in liquid environments. Building upon this, the optoelectronic nanoparticles are introduced into an injectable hydrogel system, forming a three-dimensional material system that can gel under physiological conditions and possesses near-infrared light-triggered electroresponsiveness. This design provides a novel technological pathway for constructing functional hydrogel materials with electrophysiological regulation capabilities.

[0021] This invention first prepares a stable aqueous dispersion of organic optoelectronic nanoparticles that are responsive to near-infrared light, then adjusts the pH to neutral, and then promotes collagen self-assembly through temperature crosslinking to obtain an injectable near-infrared light-responsive optoelectronic nanoparticle hydrogel.

[0022] Specifically, the preparation method of the injectable near-infrared light-responsive photoelectric nanoparticle hydrogel of the present invention includes the following steps: (1) The preparation of photoelectric nanoparticle aqueous dispersion by microemulsion method includes the following steps: adding a biocompatible surfactant (phospholipid surfactant) to deionized water, stirring at 75°C for 12 h to dissolve the surfactant, and obtaining an aqueous phase with a concentration of 1 mg / mL; since it has low solubility in deionized water, it tends to self-assemble into micelles, and should be filtered with a 0.45 μm filter before use to select nanoparticles with a particle size distribution of about 100 nm to obtain a homogeneous solution.

[0023] Among them, phospholipid surfactants can be selected from egg yolk lecithin, egg yolk phosphatidylglycerol, or sphingomyelin, etc.

[0024] Organic photoelectric semiconductors were dissolved in chloroform to form a heterostructure, yielding an oil phase with a concentration of 15 mg / mL. The organic photoelectric semiconductor was a mixture of P-type semiconductors (such as PM6, P3HT, D18, or PTQ-10) and N-type semiconductors (such as Y6, PCBM, or L8-BO), with the P-type semiconductor serving as the donor material and the N-type semiconductor as the acceptor material. The molecular formulas of PM6 and Y6 are shown below. Figure 1 In section d, the donor material and acceptor material are mixed in a bulk heterojunction (BHJ) structure, and the mass ratio of P-type semiconductor to N-type semiconductor is 1:(0.8~1.2).

[0025] Under vigorous stirring (40℃, 1500 rpm continuous stirring) of the aqueous phase, the oil phase was injected into the homogeneous solution through a syringe, and then rapidly placed in an ultrasonic crusher. The organic optoelectronic semiconductor was broken down into nanoparticles by ultrasonic crushing. Chloroform was then removed by thermal evaporation, yielding a stable, biocompatible aqueous dispersion of optoelectronic nanoparticles. The concentration of the aqueous dispersion ranged from 0.75 to 4.5 mg / mL, and the nanoparticles exhibited a uniform particle size distribution with a diameter of approximately 100 nm.

[0026] The volume ratio of the homogeneous solution to the oil phase is (8~12):1.

[0027] The ultrasonic temperature of the ultrasonic crusher is set at 15℃, the ultrasonic time is 60 mins, and the power is 170 W.

[0028] (2) Preparation of photoelectric nanoparticle hydrogels with certain strength, including the following steps: The selected hydrogel was rat tail collagen, extracted from the tail of SD rats, with an initial concentration of 5 mg / mL, dissolved in 0.006 mol / L acetic acid solution, resulting in a slightly acidic environment. Structurally, it consists of two α1 chains and one α2 chain coiled into a 300 nm long triple helix, with intermolecular stability mainly maintained by hydrogen bonds and a small amount of electrostatic interaction. Rat tail collagen is a temperature-sensitive hydrogel. At concentrations above 1 mg / mL, pH around 7, and temperatures of 37℃, the molecular chains further overlap and branch, forming a triple helix structure, resulting in a three-dimensional hydrogel with a certain strength. The specific steps are as follows: 2.1) First, add pH adjustment components to the centrifuge tube. Specifically, add 0.1 mol / L NaOH aqueous solution and 10×HBSS solution in sequence as pH adjustment components for subsequent cross-linking of rat tail collagen. The pH adjustment components can adjust the pH of collagen to neutral, weaken the molecular repulsion between collagen macromolecules, and promote the subsequent cross-linking process.

[0029] 2.2) Continue to add the photoelectric nanoparticle aqueous dispersion described in step (1) into the centrifuge tube as an effective component for the subsequent photoelectric nanoparticle hydrogel to generate photoelectric response.

[0030] 2.3) Continue to add rat tail collagen (Type I) to the centrifuge tube to prepare photoelectric nanoparticle hydrogel. At this time, the gel is stored in an ice bath at 0~4℃ and has not yet formed a three-dimensional gel with a certain strength. It will crosslink after the temperature is raised to 37℃.

[0031] (3) Adding PBS buffer to the photoelectric nanoparticle hydrogel includes the following steps: The photoelectric nanoparticle hydrogel in step (2) was mixed with an equal volume of PBS buffer at 0~4℃ and diluted to obtain a hydrogel dilution with a concentration of about 2 mg / mL. The hydrogel was then placed in a constant temperature environment of 37℃ for 10 mins to crosslink, thereby obtaining an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel. This hydrogel is injectable at low temperatures and crosslinks at 37℃.

[0032] This invention uses collagen as a biocompatible matrix and introduces near-infrared responsive BHJ optoelectronic nanoparticles into the gelation process to construct an injectable near-infrared light-responsive optoelectronic nanoparticle hydrogel that combines fluidity, rapid gelation, and uniform distribution of optoelectronic functions. It is anticipated that this injectable near-infrared light-responsive optoelectronic nanoparticle hydrogel can gel in situ at the brain injury site, thus providing a possibility for constructing a three-dimensional hydrogel material platform with wirelessly triggered electrical response characteristics. This type of material system has potential application value in neuroengineering and other related biomedical engineering fields.

[0033] All raw materials and equipment used in this invention are known products, obtained by purchasing commercially available products. Rat tail collagen (Type I, liquid, Beijing Solarbio Science & Technology Co., Ltd., specification: 5 mg / mL, dissolved in 0.006 mol / L HAc); P-type semiconductor: PM6 purchased from Dongguan Fu'an Optoelectronics; P-type semiconductor: Y6 purchased from HYPER. All reagents were used according to the manufacturer's instructions, without additional purification at the recommended dilution.

[0034] Example 1 (1) Preparation of organic optoelectronic nanoparticles coated with phospholipid surfactants by microemulsion method Preparation of aqueous and oil phase solutions: Oil phase: The mixture of PM6 and Y6 was dissolved in chloroform solution at a mass ratio of 1:1. The mixture was stirred at 40°C for 12 hours to obtain an oil phase with a total concentration of 15 mg / mL of PM6 and Y6. Aqueous phase: The phospholipid surfactant (egg yolk lecithin) was dissolved in deionized water and stirred at 75°C for 12 hours to obtain an aqueous solution of the phospholipid surfactant with a concentration of 1 mg / mL.

[0035] Aqueous and oil phase mixing: Before mixing, the aqueous solution of the phospholipid surfactant was filtered through a 0.45 μm filter. Then, under vigorous stirring conditions (40℃ hot stage, 1500 rpm), the aqueous solution of the phospholipid surfactant and the oil phase were mixed. Specifically, the oil phase was injected into the aqueous phase through a syringe, with a volume ratio of aqueous to oil phase of 10:1. The mixture was then ultrasonically broken up in an ultrasonic mixer at 170 W and a 15℃ water bath for 1 h. Solvent evaporation was then performed, and the ultrasonically broken liquid was left exposed on a 50℃ hot stage for 2 h to remove chloroform, yielding an aqueous dispersion of photoelectric nanoparticles.

[0036] Filtration and impurity removal: The aqueous dispersion of photoelectric nanoparticles after chloroform evaporation was filtered through a 0.45 μm filter to obtain a stable aqueous dispersion of photoelectric nanoparticles with a particle size distribution of approximately 100 nm. The prepared photoelectric nanoparticles exhibited significantly enhanced photoelectric effect in the 400–900 nm range, thus enabling the realization of photoelectric effect under near-infrared light response.

[0037] (2) Preparation of injectable near-infrared light-responsive nanoparticle hydrogels First, a NaOH solution for pH adjustment and 5 μL of 10×HBSS buffer were mixed. Then, a fixed volume of aqueous dispersion of photoelectric nanoparticles was added, followed by a rat tail collagen solution, to obtain a "photoelectric nanoparticle hydrogel" (pH 7-7.4) composed of photoelectric nanoparticles, HBSS, NaOH, and rat tail collagen. The matrix of the hydrogel is rat tail collagen. All the above steps were performed in an ice bath at 0-4°C, at which point the photoelectric nanoparticle hydrogel did not undergo cross-linking at low temperatures. The NaOH solution concentration is 0.1 mol / L, and the amount added is 4 μL, ensuring that the final gel pH is 7~7.4.

[0038] The amount of the fixed-volume aqueous dispersion of photoelectric nanoparticles added was 4 μL, and the concentration of the aqueous dispersion of photoelectric nanoparticles was 0.75 mg / mL. The concentration of the aqueous dispersion of photoelectric nanoparticles was obtained by centrifugal concentration.

[0039] The rat tail collagen solution was purchased from the manufacturer with an initial concentration of 5 mg / mL and stored in an ice bath at 0-4°C.

[0040] (3) Add an equal volume of PBS buffer to 60 µL of photoelectric nanoparticle hydrogel to dilute the gel components, and mix thoroughly. The above steps are performed in an ice bath at 0~4℃. Then crosslink at a constant temperature of 37℃ for 10 mins to obtain a near-infrared light-responsive organic photoelectric nanoparticle biomimetic hydrogel.

[0041] Example 2 The difference from Example 1 is that the amount of the fixed-volume photoelectric nanoparticle aqueous dispersion added is 4 μL, and the concentration of the photoelectric nanoparticle aqueous dispersion is 4.5 mg / mL, while the rest is the same as in Example 1.

[0042] Example 3 (1) Preparation of organic optoelectronic nanoparticles coated with phospholipid surfactants by microemulsion method Preparation of aqueous and oil phase solutions: Oil phase: The mixture of P3HT and PCBM was dissolved in chloroform solution at a mass ratio of 1:0.8. The mixture was stirred at 40°C for 12 hours to obtain an oil phase with a total concentration of 15 mg / mL of P3HT and PCBM. Aqueous phase: The phospholipid surfactant (egg yolk phosphatidylglycerol) was dissolved in deionized water and stirred at 75°C for 12 h to obtain an aqueous solution of the phospholipid surfactant with a concentration of 1 mg / mL.

[0043] Aqueous and oil phase mixing: Before mixing, the aqueous solution of the phospholipid surfactant was filtered through a 0.45 μm filter. Then, under vigorous stirring conditions (40℃ hot stage, 1500 rpm), the aqueous solution of the phospholipid surfactant and the oil phase were mixed. Specifically, the oil phase was injected into the aqueous phase through a syringe, with a volume ratio of aqueous to oil phase of 8:1. The mixture was then ultrasonically broken up in an ultrasonic mixer at 170 W and a 15℃ water bath for 1 h. Solvent evaporation was then performed, and the ultrasonically broken liquid was left exposed on a 50℃ hot stage for 2 h to remove chloroform, yielding an aqueous dispersion of photoelectric nanoparticles with a concentration of 1 mg / mL.

[0044] Filtration and impurity removal: The aqueous dispersion of photoelectric nanoparticles after chloroform evaporation was filtered through a 0.45 μm filter to obtain a stable aqueous dispersion of photoelectric nanoparticles with a particle size distribution of approximately 100 nm. The prepared photoelectric nanoparticles exhibited significantly enhanced photoelectric effect in the 400–900 nm range, thus enabling the realization of photoelectric effect under near-infrared light response.

[0045] (2) Same as Example 1; (3) Same as Example 1.

[0046] Example 4 (1) Preparation of organic optoelectronic nanoparticles coated with phospholipid surfactants by microemulsion method Preparation of aqueous and oil phase solutions: Oil phase: The mixture of D18 and L8-BO was dissolved in chloroform solution at a mass ratio of 1:1.2. The mixture was stirred at 40°C for 12 hours to obtain an oil phase with a total concentration of 15 mg / mL of D18 and L8-BO. Aqueous phase: The phospholipid surfactant (sphingomyelin) was dissolved in deionized water and stirred at 75°C for 12 hours to obtain an aqueous solution of the phospholipid surfactant with a concentration of 1 mg / mL.

[0047] Aqueous and oil phase mixing: Before mixing, the aqueous solution of the phospholipid surfactant was filtered through a 0.45 μm filter. Then, under vigorous stirring conditions (40℃ hot stage, 1500 rpm), the aqueous solution of the phospholipid surfactant and the oil phase were mixed. Specifically, the oil phase was injected into the aqueous phase through a syringe, with a volume ratio of aqueous to oil phase of 12:1. The mixture was then ultrasonically broken up in an ultrasonic mixer at 170 W and a 15℃ water bath for 1 h. Solvent evaporation was then performed, and the ultrasonically broken liquid was left exposed on a 50℃ hot stage for 2 h to remove chloroform, yielding an aqueous dispersion of photoelectric nanoparticles with a concentration of 2 mg / mL.

[0048] Filtration and impurity removal: The aqueous dispersion of photoelectric nanoparticles after chloroform evaporation was filtered through a 0.45 μm filter to obtain a stable aqueous dispersion of photoelectric nanoparticles with a particle size distribution of approximately 100 nm. The prepared photoelectric nanoparticles exhibited significantly enhanced photoelectric effect in the 400–900 nm range, thus enabling the realization of photoelectric effect under near-infrared light response.

[0049] (2) Same as Example 1; (3) Same as Example 1.

[0050] Example 5 (1) Preparation of organic optoelectronic nanoparticles coated with phospholipid surfactants by microemulsion method Preparation of aqueous and oil phase solutions: Oil phase: The mixture of PTQ-10 and Y6 was dissolved in chloroform solution at a mass ratio of PTQ-10 to Y6 of 1:0.9. The mixture was stirred at 40°C for 12 hours to obtain an oil phase with a total concentration of PTQ-10 and Y6 of 15 mg / mL. Aqueous phase: The phospholipid surfactant (egg yolk lecithin) was dissolved in deionized water and stirred at 75°C for 12 hours to obtain an aqueous solution of the phospholipid surfactant with a concentration of 1 mg / mL.

[0051] Aqueous and oil phase mixing: Before mixing, the aqueous solution of the phospholipid surfactant was filtered through a 0.45 μm filter. Then, under vigorous stirring conditions (40℃ hot stage, 1500 rpm), the aqueous solution of the phospholipid surfactant and the oil phase were mixed. Specifically, the oil phase was injected into the aqueous phase through a syringe, with a volume ratio of aqueous to oil phase of 11:1. The mixture was then ultrasonically broken up in an ultrasonic mixer at 170 W and a 15℃ water bath for 1 h. Solvent evaporation was then performed, and the ultrasonically broken liquid was left exposed on a 50℃ hot stage for 2 h to remove chloroform, yielding an aqueous dispersion of photoelectric nanoparticles with a concentration of 3 mg / mL.

[0052] Filtration and impurity removal: The aqueous dispersion of photoelectric nanoparticles after chloroform evaporation was filtered through a 0.45 μm filter to obtain a stable aqueous dispersion of photoelectric nanoparticles with a particle size distribution of approximately 100 nm. The prepared photoelectric nanoparticles exhibited significantly enhanced photoelectric effect in the 400–900 nm range, thus enabling the realization of photoelectric effect under near-infrared light response.

[0053] (2) Same as Example 1; (3) Same as Example 1.

[0054] Comparative Example 1 The difference from Example 1 is that the amount of 0.1 mol / L NaOH solution added is 3 μL, while the rest is the same as in Example 1.

[0055] Comparative Example 2 The difference from Example 1 is that the amount of 0.1 mol / L NaOH solution added is 5 μL, while the rest is the same as in Example 1.

[0056] After the gel was placed at 37°C for 10 min, it did not crosslink and remained liquid. This indicates that the injectable photoelectric nanoparticle hydrogel is highly sensitive to pH, requiring the addition of a precise amount of 0.1 mol / L NaOH (4 μL of 0.1 mol / L NaOH solution per 60 μL of rat tail collagen) to adjust the pH of the system to neutral before crosslinking conditions can be achieved. This result confirms that the injectable photoelectric nanoparticle hydrogel described in this invention has a narrow pH window dependence: when the amount of 0.1 mol / L NaOH is below 3 µL, the system pH is < 6.8, the surface positive charge density of the collagen triple helix is ​​high, and the electrostatic repulsion between chains inhibits entanglement; when it is above 5 µL, the pH is > 7.6, and the collagen undergoes excessive deprotonation, which also hinders the crosslinking process. Only when the amount of NaOH added is 4 µL (corresponding to 60 µL of collagen) is the pH of the system precisely locked at 7.0–7.4, and the hydrogen bonds and hydrophobic interactions between the collagen α1 / α2 chains reach equilibrium, can the system rapidly self-assemble into a gel network at 37 °C. Therefore, the amount of 0.1 mol / L NaOH must be strictly controlled within the range of 4 µL per 60 µL of rat tail collagen; deviation from this value will lead to cross-linking failure.

[0057] Comparative Example 3 The only difference from Example 1 is that the amount of PBS buffer added is changed to 100 µL of PBS buffer for every 60 µL of rat tail collagen (the same volume of 60 µL in Example 1), and everything else is the same as in Example 1.

[0058] After incubation at 37 °C for 10 min, the system still maintained its flow dynamics. This result indicates that this system also has a critical window for the final collagen concentration: when the dilution factor is >1.7 times, the final collagen concentration is low, the probability of interchain collisions is significantly reduced, and effective cross-linking sites cannot be formed; while in Example 1, a 1:1 volume ratio was maintained (final concentration ≈2 mg / mL). -1 Cross-linking can be completed within 10 minutes at 37 °C. Therefore, the amount of PBS buffer added should be limited to no more than 1 times the volume of the collagen solution to ensure that the collagen chain density is sufficient to drive three-dimensional entanglement and achieve rapid injectable gelation.

[0059] The following is the testing process: (1) Characterization of photoelectric nanoparticles prepared by microemulsion method mainly includes particle size and particle size distribution testing and ultraviolet-visible spectrophotometry testing.

[0060] Test Methods: For the particle size and distribution testing of the prepared nanoparticles, dynamic light scattering (DLS) was used. A Malvern Zetasizer Nano was used to characterize the hydrodynamic diameter and particle size distribution of the nanoparticles. The specific steps were as follows: The nanoparticle dispersion to be tested was diluted with deionized water to a suitable concentration (usually 0.1-1 mg / mL), and 1 mL was placed in a quartz cuvette. Measurements were performed using a 633 nm laser source under a constant temperature of 25°C. The instrument analyzed the autocorrelation function of the scattered light intensity, processed it using a cumulative algorithm, and finally reported the Z-Average average hydrodynamic diameter and polydispersity index (PDI) of the nanoparticles to characterize their average size and distribution uniformity. For UV-Vis spectrophotometry, a Shimadzu UV-3600 UV-Vis spectrophotometer was used, with deionized water as a reference solution for baseline correction. The aqueous dispersion of the nanoparticles to be tested was appropriately diluted with deionized water to ensure that its maximum absorbance value was within the linear response range of the instrument. Take an appropriate amount of the diluted sample solution and place it in a standard quartz cuvette. At room temperature, perform a full-spectrum scan at a medium speed within the wavelength range of 400-900 nm. Record the absorption spectrum and obtain the position (λ) of the characteristic absorption peak of the nanoparticles and the absorbance value at the corresponding wavelength for analysis of their optical absorption characteristics.

[0061] Test results: DLS testing showed that the nanoparticles coated with phospholipid surfactants had a particle size distribution of approximately 100 nm, a polydispersity index (PDI) of 0.225, and a relatively uniform particle size distribution, indicating that the prepared photoelectric nanoparticle aqueous dispersion system was relatively stable. Figure 1 (a) UV-Vis spectrophotometer tests showed that, compared with pure chloroform solution of PM6:Y6, PM6:Y6 nanoparticles coated with phospholipid surfactants exhibited stronger absorption in the near-infrared region. Figure 1 (b) provides support for subsequent near-infrared light-excited photoelectric conversion; cryo-electron microscopy shows that the prepared photoelectric nanoparticles have a near-spherical morphology ( Figure 1 (c)

[0062] (2) Characterization of injectable near-infrared light-responsive nanoparticle hydrogels mainly includes scanning electron microscopy (SEM) testing, ultraviolet-visible spectrophotometry, injectability performance characterization, and patch clamp testing.

[0063] Test Method: SEM Test: To observe the microstructure and three-dimensional porous structure of near-infrared light-responsive nanoparticle hydrogels, SEM samples were prepared using a freeze-drying method. The specific steps are as follows: An appropriate amount of the hydrogel sample prepared in the example was taken and rapidly quenched in liquid nitrogen to minimize the damage to the structure caused by ice crystal growth. The completely frozen sample was quickly transferred to a freeze dryer and sublimated at a condenser temperature below -50°C and a vacuum degree below 10 Pa for at least 48 hours until completely dry. The resulting dried gel was fractured to expose a fresh cross-section, which was then fixed on the sample stage. A gold conductive layer of approximately 5-10 nm thickness was uniformly sprayed onto the cross-section surface using an ion sputtering instrument, and the sample was placed in the sample chamber of a scanning electron microscope (ZeissGemini). The surface and cross-sectional morphology were observed and photographed in secondary electron imaging mode at an accelerating voltage of 3.0 kV to analyze the hydrogel's network structure, pore size distribution, and nanoparticle dispersion state.

[0064] The UV-Vis spectrophotometric testing process is similar to that used in the characterization of organic optoelectronic nanoparticles, except that hydrogels without nanoparticles and optoelectronic nanoparticle hydrogels are coated separately onto clean glass slides for testing solid samples. Mechanical properties and patch-clamp testing: Patch-clamp technique is used to record the photocurrent of the near-infrared light-responsive nanoparticle hydrogels. The hydrogel sample is fixed in a recording chamber continuously perfused with physiological saline solution. Using a glass microelectrode (resistance 3-6 MΩ) filled with the same electrolyte, its tip is brought into contact with the gel surface under direct microscopic observation. A gigaohm (GΩ) high-resistance seal is formed through negative pressure, establishing a stable electrical connection. The electrode tip region is irradiated with a focused near-infrared laser for 1 s and 500 ms. The induced current signal during illumination is recorded and analyzed to quantitatively characterize the photoelectric conversion performance of the hydrogel.

[0065] Test results: SEM analysis showed that the near-infrared photoresponsive nanoparticle hydrogel has a porous structure with a pore size of approximately 300~500 μm. Figure 2 (a); UV-Vis spectrophotometry showed that the near-infrared light-responsive nanoparticle hydrogel absorbed in the near-infrared region. Figure 2(b) This provides support for subsequent near-infrared light-excited photoelectric conversion. Patch-clamp tests show that under pulsed light (wavelength 564 nm) irradiation, the photocurrent of the photoelectric nanoparticle hydrogel is approximately 20 pA ( Figure 4 (a and b). Meanwhile, the PM6:Y6 pure film, under three-electrode, 850 nm near-infrared light testing conditions, can generate photocurrent ( Figure 4 c) See Figure 3 As shown in a and b, the injectable near-infrared light-responsive optoelectronic nanoparticle hydrogel is expected to be configured at low temperatures and cross-linked in situ at physiological temperatures. Under near-infrared light irradiation, the material system can generate a stable and controllable electrical response signal, thus providing the possibility for constructing a three-dimensional hydrogel material platform with wireless light-triggered electrical response characteristics.

[0066] This invention utilizes a microemulsion process to prepare near-infrared responsive bulk heterojunction photoelectric nanoparticles, enabling controllable photocharge generation in a humid environment. By uniformly embedding these photoelectric nanoparticles into a gel network, a three-dimensional material system exhibiting stable photoelectric response characteristics in a humid environment is constructed. This system is innovative in its material composition, gelation mechanism, and photoelectric functional integration, providing a new material platform for the research and application of related functional hydrogel materials.

[0067] The above description is only of the preferred embodiment of the present invention and should not be construed as limiting the scope of the claims. The present invention is not limited to the above embodiments, and variations in its specific structure are permitted. All variations made within the scope of the independent claims of the present invention are also within the scope of protection of the present invention.

[0068] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

Claims

1. A method for preparing an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel, characterized in that, Includes the following steps: A hydrogel of photoelectric nanoparticles containing surfactants and organic photoelectric semiconductors, along with rat tail collagen, was added to a mixed solution of NaOH aqueous solution and HBSS solution to obtain a hydrogel of photoelectric nanoparticles. The photoelectric nanoparticle hydrogel was mixed with an equal volume of PBS buffer to obtain a hydrogel dilution. The hydrogel dilution was then crosslinked to obtain an injectable near-infrared light-responsive photoelectric nanoparticle hydrogel.

2. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 1, characterized in that, An aqueous dispersion of optoelectronic nanoparticles containing surfactants and organic optoelectronic semiconductors is prepared by the following process: Add a surfactant to water, dissolve it, filter it, and obtain the aqueous phase. An organic photoelectric semiconductor was dissolved in chloroform to obtain an oil phase; wherein the organic photoelectric semiconductor was a mixture of P-type and N-type semiconductors. The oil phase was added to the aqueous phase, and the mixture was subjected to ultrasound and heating to obtain an aqueous dispersion of photoelectric nanoparticles.

3. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 1, characterized in that, The surfactant is a phospholipid surfactant.

4. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 3, characterized in that, Phospholipid surfactants include egg yolk lecithin, egg yolk phosphatidylglycerol, or sphingomyelin.

5. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 2, characterized in that, The concentration of the aqueous phase was 1 mg / mL, and the concentration of the oil phase was 15 mg / mL; the volume ratio of the aqueous phase to the oil phase was (8~12):

1.

6. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 2, characterized in that, P-type semiconductors are designated PM6, P3HT, D18, or PTQ-10, while N-type semiconductors are designated Y6, PCBM, or L8-BO.

7. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 2, characterized in that, The mass ratio of P-type semiconductors to N-type semiconductors is 1:(0.8~1.2).

8. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 1, characterized in that, The pH of the optoelectronic nanoparticle hydrogel is 7-7.4; the concentration of the hydrogel diluent is 2 mg / mL.

9. The method for preparing injectable near-infrared light-responsive photoelectric nanoparticle hydrogel according to claim 1, characterized in that, The cross-linking temperature was 37℃ and the time was 10 min.

10. An injectable near-infrared photoresponsive photoelectric nanoparticle hydrogel prepared by any one of claims 1-9.

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