Bioactive materials with anti-inflammatory functions, biomaterials and their applications

Abstract

This invention relates to the field of biomedicine and discloses a bioactive material with anti-inflammatory function, biomaterials, and their applications. This invention innovatively conjugates compounds with specific structures and functions to photosynthetic materials, forming a bioactive material capable of more efficiently converting light energy into ATP and NADPH in animals. This bioactive material can effectively improve the energy metabolism imbalance within inflammatory cells.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a bioactive material with anti-inflammatory function, biomaterials, and their applications. Background Technology

[0002] Inflammation is widely recognized as playing a key role in the development of various diseases. Studies have shown that inflammation can induce mitochondrial dysfunction in cells, causing energy metabolism disorders and ultimately leading to organ dysfunction.

[0003] Current treatments for inflammation, such as cell therapy, nanomedicine, and gene therapy, often fail to address the intracellular energy imbalance caused by inflammation. Furthermore, because mitochondrial metabolic dysfunction in inflamed cells significantly reduces the production of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH), exogenous ATP cannot diffuse into the cell membrane, and the supply of exogenous ATP and NADPH cannot regulate the endogenous metabolic network, there are currently few effective treatments or technologies for inflammation from the perspective of regulating energy metabolism. Summary of the Invention

[0004] The purpose of this invention is to overcome the problems of the lack of effective treatments for inflammation and the resulting intracellular energy metabolism disorders in the existing technology, and to provide a bioactive material with anti-inflammatory function, a biomaterial, and their applications.

[0005] To achieve the above objectives, the present invention provides a bioactive material with anti-inflammatory function, wherein the bioactive material comprises a conjugated compound and a photosynthetic material connected by electrostatic and hydrophobic interactions, and the conjugated compound has the effect of promoting the spectral absorption capacity of the photosynthetic material.

[0006] A second aspect of the present invention provides a biomaterial comprising a cell membrane and a bioactive material loaded on the cell membrane, wherein the bioactive material is the bioactive material described in the first aspect.

[0007] The third aspect of this invention provides the use of the bioactive material described in the first aspect, or the biomaterial described in the second aspect, in improving intracellular energy imbalance, particularly in increasing the content of intracellular adenosine triphosphate and / or nicotinamide adenine dinucleotide phosphate.

[0008] The fourth aspect of the present invention provides the use of the bioactive material described in the first aspect, or the biomaterial described in the second aspect, in the preparation of a medicament for treating inflammation.

[0009] The fifth aspect of the present invention provides a method for improving inflammation in cell cultures in vitro, the method comprising:

[0010] (1) Introducing the bioactive material described in the first aspect into a cell culture with inflammatory characteristics, or contacting the biomaterial described in the second aspect with a cell culture with inflammatory characteristics;

[0011] (2) Treat the cell culture with light.

[0012] Through the above technical solution, the present invention can achieve at least the following beneficial effects:

[0013] (1) This invention innovatively connects a specific polymer with a photosynthetic material in a conjugate manner, which improves the ability of the photosynthetic material to convert light energy into ATP and NADPH in the animal body, thereby improving the problem of energy metabolism imbalance in cells.

[0014] (2) The bioactive material provided by the present invention has good biocompatibility after being loaded onto the cell membrane, and has good effects on the treatment and improvement of inflammation in vivo and in vitro.

[0015] (3) The biomaterials provided by the present invention have been experimentally verified to effectively improve the metabolic disorder of organoids and have good therapeutic effects on organoids with inflammation modeling, and have the potential to be used as active ingredients for novel anti-inflammatory drugs. Attached Figure Description

[0016] Figure 1 These are the ultraviolet absorption and fluorescence emission spectra of the polymer synthesized in Example 1.

[0017] Figure 2 This is the ITC diagram of PBF titration onto nano-thylakoids in Example 1.

[0018] Figure 3 This is a graph showing the zeta potential detection results of the bioactive material in Example 1.

[0019] Figure 4 The results are the NADPH yield detection results of the bioactive material prepared in Example 1 after light treatment.

[0020] Figure 5 This is a comparison chart of the DLS particle size distribution results of the bioactive material before and after cell membrane coating in Example 2.

[0021] Figure 6 This is a graph showing the ATP production results of the inflammatory organoids in Test Example 1 after different treatments.

[0022] Figure 7 This is a graph showing the NADPH production results of the inflammatory organoids in Test Example 1 after different treatments.

[0023] Figure 8This is a graph showing the GSEA pathway enrichment detection results of inflammatory organoids after different treatments in Test Example 1.

[0024] Figure 9 The image shows the results of gene expression level detection of the inflammatory factor IL-6 in the inflammatory organoids after different treatments in Test Example 1. Detailed Implementation

[0025] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0026] By encapsulating conjugated molecules with biocompatible photosynthetic materials that absorb light and release oxygen within cell membranes, ATP and NADPH can be controllably provided in model organisms, potentially addressing energy metabolism disorders caused by inflammation. However, the inventors of this invention discovered that the spectral absorption capacity of photosynthetic pigments on the surface of biocompatible photosynthetic materials prepared in this way is limited, thus restricting the efficiency of light energy conversion and resulting in unsatisfactory energy metabolism regulation. Through extensive research, the inventors ingeniously discovered that by further combining photosynthetic materials with substances that enhance their spectral absorption capacity, and then using biocompatible materials such as cell membranes to load the photosynthetic materials and the substances enhancing their spectral absorption capacity, the ATP and NADPH synthesis capacity of the photosynthetic materials in vivo can be effectively improved, promoting improved energy metabolism and the treatment of inflammation.

[0027] Based on this, the first aspect of the present invention provides a bioactive material with anti-inflammatory function, the bioactive material comprising a conjugated compound and a photosynthetic material connected by electrostatic and hydrophobic interactions, wherein the conjugated compound has the effect of promoting the spectral absorption capacity of the photosynthetic material.

[0028] The compounds used in the bioactive materials provided by this invention are compounds that can promote the spectral absorption capacity of photosynthetic materials without affecting their normal function or having minimal impact on them. Furthermore, these compounds should not have adverse effects on cells and organisms. Any compound that meets the above requirements is applicable to this invention.

[0029] According to some preferred embodiments of the present invention, the compound is selected from at least one of boron dipyrrole methylene (BODIPY) and its water-soluble derivatives.

[0030] In this invention, water-soluble derivatives of BODIPY refer to salts, acids, or bases formed based on BODIPY. Alternatively, they can be water-soluble compounds with a similar skeleton to BODIPY, such as water-soluble polymers formed by BODIPY as a structural unit, or water-soluble polymers formed by BODIPY and compounds with a similar skeleton structure as structural units. Compounds with a similar skeleton structure to BODIPY can include compounds in which several groups are further substituted on the structure of BODIPY, or derivative compounds formed by further connecting other groups to the structure of BODIPY (the connecting groups can include straight-chain or branched alkyl groups with 10 or fewer carbon atoms, cycloalkyl groups with 10 or fewer carbon atoms, aryl groups, N-containing heterocycles with 10 or fewer carbon atoms, S-containing heterocycles with 10 or fewer carbon atoms, ether bonds, ester groups with 10 or fewer carbon atoms, etc.).

[0031] According to some preferred embodiments of the present invention, the compound has the structure shown in formula (I):

[0032]

[0033] In formula (I), a is any integer from 1 to 100 (preferably any integer from 5 to 30), b is any integer from 1 to 100 (preferably any integer from 5 to 30), n is any integer from 1 to 100 (preferably any integer from 5 to 30), and X is F, Cl, Br, or I.

[0034] For example, in equation (I), a, b, or n can be 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30, respectively.

[0035] Preferably, in formula (I), a, b, and n can be the same or different.

[0036] According to a particularly preferred embodiment of the present invention, the compound has the structure shown in formula (II):

[0037]

[0038] Preferably, the number-average molecular weight of the compound is 20,000-50,000 g / mol, and more preferably 30,000-40,000 g / mol.

[0039] In this invention, photosynthetic materials refer to substances capable of photosynthesis. Any substance capable of photosynthesis can be used in this invention; it can be a natural photosynthetic material or an artificially modified photosynthetic material.

[0040] According to some preferred embodiments of the present invention, the photosynthetic material is selected from at least one of algae, chloroplasts and thylakoids, or the photosynthetic material is prepared from algae, chloroplasts and thylakoids.

[0041] Preferably, the photosynthetic material can be prepared from thylakoids, for example, nanothylakoids. "Nanothylakoids" refer to photosynthetically active modular thylakoids obtained by breaking down thylakoids (e.g., materials formed by breaking down the multilayer structure of thylakoids into a single-layer structure). Preferably, the breaking down method is ultrasonic breaking.

[0042] According to a preferred embodiment of the present invention, the concentration of the compound in the bioactive material is 1-20 μM relative to 10 μg / mL of the photosynthetic material.

[0043] For example, relative to 10 μg / mL of the photosynthetic material, the concentration of the compound can be 1 μM, 2 μM, 3 μM, 4 μM, 5 μM, 6 μM, 7 μM, 8 μM, 9 μM, 10 μM, 11 μM, 12 μM, 13 μM, 14 μM, 15 μM, 16 μM, 17 μM, 18 μM, 19 μM, 20 μM, or a range consisting of any two of the above values, or any intermediate value within that range.

[0044] Preferably, the surface potential (Zeta potential) of the bioactive material is -10 to -25 mV, more preferably -10 to -20 mV. For example, it can be -10 mV, -11 mV, -12 mV, -13 mV, -14 mV, -15 mV, -16 mV, -17 mV, -18 mV, -19 mV, -20 mV, or any range consisting of any two of the above values, or any intermediate value within that range.

[0045] The present invention further provides a method for preparing the above-mentioned bioactive material. According to a preferred embodiment of the present invention, the method includes contacting the above-mentioned compound with a photosynthetic material, thereby forming the above-mentioned bioactive material through self-assembly.

[0046] Preferably, the contact conditions include: the concentration of the compound is 1-20 μM, preferably 1-16 μM; the concentration of the photosynthetic material is 10-100 μg / mL, preferably 10-30 μg / mL; the contact temperature is 4-37℃, preferably 4-25℃; and the contact time is 1-50 min, preferably 5-15 min.

[0047] For example, the concentration of the compound can be 1 μM, 2 μM, 4 μM, 6 μM, 8 μM, 10 μM, 12 μM, 14 μM, 16 μM, or a range consisting of any two of the above values, or any intermediate value within that range.

[0048] For example, the concentration of photosynthetic material can be 10 μg / mL, 12 μg / mL, 14 μg / mL, 16 μg / mL, 18 μg / mL, 20 μg / mL, 22 μg / mL, 24 μg / mL, 26 μg / mL, 28 μg / mL, 30 μg / mL, or any range consisting of any two of the above values, or any intermediate value within that range.

[0049] For example, the contact temperature can be 4℃, 6℃, 8℃, 10℃, 12℃, 14℃, 16℃, 18℃, 20℃, 22℃, 24℃, or 25℃, or it can be any range of any two of the above values, or any intermediate value within that range.

[0050] For example, the contact time can be 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min, or 15 min, or it can be a range consisting of any two of the above values, or any intermediate value within that range.

[0051] A second aspect of the present invention provides a biomaterial comprising a cell membrane and a bioactive material loaded on the cell membrane, wherein the bioactive material is the bioactive material described in the first aspect.

[0052] According to a preferred embodiment of the present invention, the cell membrane is selected from cell membranes derived from mammalian cells, preferably human cell membranes.

[0053] Preferably, the cell membrane is selected from at least one of (human) cancer cell membranes, (human) stem cell membranes, and (human) immune cell membranes.

[0054] More preferably, the cell membrane is selected from at least one of human breast cancer cell membrane, human liver cancer cell membrane, human pluripotent stem cell membrane, human mesenchymal stem cell membrane, and human macrophage cell membrane.

[0055] According to a preferred embodiment of the present invention, the cell membrane is a cell membrane capable of targeting inflammatory features (e.g., the cell membrane surface contains inflammatory-targeting proteins).

[0056] In this invention, the cell membrane used to prepare biomaterials can be prepared by any method commonly used in the art, or related products can be purchased through commercial or custom channels.

[0057] The present invention further provides a method for preparing the above-mentioned biomaterial. According to a preferred embodiment of the present invention, the method includes coating the bioactive material described in the first aspect with a cell membrane. Any method commonly used in the art for coating bioactive materials with a cell membrane is applicable to the present invention; for example, extrusion can be used to prepare the biomaterial provided by the present invention.

[0058] The third aspect of this invention provides the use of the bioactive material described in the first aspect, or the biomaterial described in the second aspect, in improving intracellular energy imbalances, particularly in increasing the levels of intracellular adenosine triphosphate (ATP) and / or nicotinamide adenine dinucleotide phosphate (NADPH).

[0059] According to a preferred embodiment of the present invention, the application may include introducing the bioactive material provided by the present invention into cells, or contacting the biomaterial provided by the present invention with cells and inducing the photosynthetic material in the bioactive material to convert light energy under light conditions, thereby generating ATP and / or NADPH.

[0060] The applications provided by this invention can be therapeutic or non-therapeutic. For example, therapeutic applications may include applying the bioactive materials or biomaterials provided by this invention to subjects (such as humans, laboratory animals, etc.) to improve energy metabolism disorders caused by inflammation by converting light energy into ATP / NADPH within the subject's cells, thereby treating the inflammation. Non-therapeutic applications may include applying the bioactive materials or biomaterials provided by this invention to in vitro cultured cells or organoids, etc., to conduct research on cellular energy metabolism disorders and treatment, inflammation mechanisms and treatment, or to perform drug screening and drug efficacy testing.

[0061] The fourth aspect of the present invention provides the use of the bioactive material described in the first aspect, or the biomaterial described in the second aspect, in the preparation of a medicament for treating inflammation.

[0062] Furthermore, the present invention also provides a treatment method for inflammation, the method comprising administering the bioactive material or biological material provided by the present invention to a subject in need at a therapeutically effective amount.

[0063] Preferably, the method further includes exposing the subject to light for a period of time so that the photosynthetic material in the bioactive material / biomaterial converts light energy into ATP / NADPH.

[0064] The fifth aspect of the present invention provides a method for improving inflammation in cell cultures in vitro, the method comprising:

[0065] (1) Introducing the bioactive material described in the first aspect into a cell culture with inflammatory characteristics, or contacting the biomaterial described in the second aspect with a cell culture with inflammatory characteristics;

[0066] (2) Treat the cell culture with light.

[0067] In this invention, the inflammatory characteristics of cell cultures can be determined by qualitative or quantitative detection of the presence and content of inflammation-related cytokines.

[0068] In this invention, cell culture refers to a culture product obtained by culturing cells (in vitro). It can be a cell (line) obtained by 2D culture, a 3D cultured cell obtained by 3D culture, or an organoid formed by further induction, etc.

[0069] According to a preferred embodiment of the present invention, the cell culture is selected from cells and / or organoids cultured in vitro.

[0070] Any in vitro cultured organoids can be treated using the above method to improve inflammatory conditions. Preferably, the organoids are selected from at least one of brain organoids, heart organoids, liver organoids, pancreatic organoids, and intestinal organoids.

[0071] According to some preferred embodiments of the present invention, in step (1), the contact time is 1-50h, preferably 5-30h.

[0072] According to a preferred embodiment of the present invention, in step (2), the conditions for the light treatment include: light intensity of 1-50 mW / cm². 2 Preferred value: 1-25mW / cm 2 Irradiation time: 5-60 min, preferably 10-30 min.

[0073] The present invention will be described in detail below through embodiments. It should be understood that the following embodiments are only used to further explain and illustrate the content of the present invention by way of example, and are not intended to limit the present invention.

[0074] In the following examples, nanothylakoids prepared according to the method in Reference 1 were used to prepare bioactive materials and biomaterials. Unless otherwise specified, all reagents and materials used were commercially available products from reputable biological or chemical reagent / material suppliers, and all reagents were of analytical grade.

[0075] Example 1

[0076] This embodiment illustrates the preparation and characteristics of the bioactive materials provided by the present invention.

[0077] (1) Preparation of compounds with structures as shown in formula (II)

[0078]

[0079] The compound shown in formula (II) was synthesized according to the method described in reference 2. The number-average molecular weight of the obtained compound was approximately 33324 g / mol.

[0080] The UV absorption and fluorescence emission of the synthesized compound were detected using a JASCO-V730 UV spectrophotometer and a Hitachi F-4500 fluorescence spectrometer. The results were normalized. For detailed results, please refer to [link to relevant documentation]. Figure 1 .

[0081] (2) Preparation of bioactive materials

[0082] The compound obtained in step (1) was prepared into a compound solution using PBS buffer at concentration gradients of 0 (i.e., PBS without the compound), 1 μM, 4 μM, and 16 μM.

[0083] The nano-thylakoids and the compound solution were mixed at a concentration ratio of 2.5 μg / mL nano-thylakoids to 1 μM compound. The mixing operation was carried out at 4°C. After mixing, the mixture was allowed to stand at 4°C for 15 min to allow it to self-assemble and form a conjugated complex of nano-thylakoids and the compound (i.e., the bioactive material in this invention).

[0084] This self-assembly behavior was demonstrated by isothermal titration calorimetry (ITC) testing to be due to electrostatic and hydrophobic interactions. For detailed ITC test results, please refer to [link to relevant documentation]. Figure 2 .

[0085] After self-assembly, the Zeta potential of each conjugated complex solution was measured. See the results for details. Figure 3 .

[0086] The solutions of the self-assembled conjugates were subjected to light treatment (white light, light intensity 3 mW / cm²). 2 The illumination time was 15 min, and then the NADPH production was measured. The specific measurement was performed according to the method in reference 1. See the results for details. Figure 4 .

[0087] Example 2

[0088] This embodiment illustrates the preparation and characteristics of the biomaterials provided by the present invention.

[0089] Cell membranes of human mesenchymal stem cells (purchased from Wuhan Pronosai Company) were extracted using the method described in Reference 3. The extracted cell membranes were then mixed with a conjugated complex solution prepared in Example 1 (the concentration of the compound in the conjugated complex was 4 μM), and the mixture was placed on a shaker at 4°C and allowed to interact for 30 min under shaking conditions. The cell membrane solution and the conjugated complex solution were mixed in equal volumes.

[0090] The cell membrane is encapsulated with conjugated compounds by extrusion. The specific operation includes: using an Avanti micro extruder to extrude a mixture of cell membrane and conjugated compounds sequentially through 1000nm, 400nm and 200nm polycarbonate porous membranes, and then centrifuging to obtain the solid phase, which is the biomaterial with cell membrane encapsulated conjugated compounds.

[0091] The particle size of DLS in the bioactive material before and after cell membrane coating was measured. See details below. Figure 5 .

[0092] Test Example 1

[0093] This test case is used to verify the efficacy of the biomaterials provided by the present invention in regulating energy metabolism disorders and treating inflammation.

[0094] (1) Construction of inflammatory organoid models

[0095] The construction process of cardiac organoids was as follows: Embryonic stem cells were seeded at a density of 10,000 cells per well in low-adsorption 96-well plates, and 100 μL of mTesr-E8 medium was added to each well. The plates were then cultured at 37°C in a 5% CO2 environment. After 24 h of culture, 50 μL of medium was aspirated and 200 μL of fresh mTesr-E8 medium was added. After another 24 h of culture, two-thirds of the medium was aspirated and RPMI-1640+B27-insulin medium containing activin A (final concentration 1 ng / mL), BMP-4 (final concentration 1.5 ng / mL), and CHIR99021 (final concentration 6 μM) was added (RPMI-1640:B27-insulin volume ratio 50:1). After culturing for another 24 hours, aspirate 2 / 3 of the culture medium and add an equal volume of RPMI-1640+B27-insulin medium (RPMI-1640:B27-insulin volume ratio 50:1). After culturing for another 24 hours, aspirate 2 / 3 of the culture medium and add an equal volume of RPMI-1640+B27-insulin medium containing Wnt-C59 (final concentration 2 μM) (RPMI-1640:B27-insulin volume ratio 50:1). After culturing for another 48 hours, aspirate 2 / 3 of the culture medium and add an equal volume of RPMI-1640+B27-insulin medium (RPMI-1640:B27-insulin volume ratio 50:1). After 48 hours of continued culture, 2 / 3 of the culture medium was aspirated and an equal volume of RPMI-1640+B27 medium (RPMI-1640:B27 volume ratio of 50:1) was added. After another 24 hours, the culture was stimulated for 1 hour with RPMI-1640+B27 medium containing CHIR99021 (final concentration 2 μM) (RPMI-1640:B27-insulin volume ratio of 50:1), and then cultured in RPMI-1640+B27 medium (RPMI-1640:B27-insulin volume ratio of 50:1) until day 17 (day 0 when embryonic stem cells are seeded in low-adsorption 96-well plates). During this period, the medium was changed every 2 days with RPMI-1640+B27 medium (RPMI-1640:B27-insulin volume ratio of 50:1).

[0096] An inflammatory cardiac organoid model was constructed by co-incubating cardiac organoids with 10 ng / mL IL-1β for 48 hours. The results showed that, compared with the cardiac organoids before co-incubation, the expression of inflammatory factors (such as IL-6) was upregulated in this inflammatory cardiac organoid model.

[0097] (2) Regulation of energy metabolism disorders and treatment of inflammation

[0098] Take the biomaterial prepared in Example 2, add 100 μL of biomaterial and mix with the inflamed cardiac organoid, and then place it at 37°C for static incubation for 8 hours.

[0099] After incubation, light treatment for 15 minutes (white light, light intensity 3mW / cm²) was applied. 2 ).

[0100] The following methods were used to evaluate the therapeutic effects of organoid inflammation and its regulatory effects on energy metabolism disorders:

[0101] 1) Detection of ATP and NADPH production in organoids, the specific methods are as follows:

[0102] ATP in organoids under different treatments was detected using the ATP-enhanced kit from Shanghai Beyotime Biotechnology Co., Ltd. Results are detailed below. Figure 6 In the figure, "+" indicates that the test material has undergone relevant treatment, and "-" indicates that the test material has not undergone relevant treatment. As can be seen from the figure, after inflammation modeling, the ATP production of organoids decreased significantly. However, when the biomaterials provided by this invention were used to contact the inflamed organoids and subjected to light treatment, the ATP level in the organoids increased significantly, even exceeding that of organoids without inflammation modeling.

[0103] The method described in Reference 1 was used to detect NADPH in organoids treated with different methods. See the results below. Figure 7 In the figure, "+" indicates that the test material has undergone relevant treatment, and "-" indicates that the test material has not undergone relevant treatment. As can be seen from the figure, after inflammation modeling, the NADPH production of organoids decreased significantly, while when the biomaterial provided by this invention was used to contact the inflamed organoids and subjected to light treatment, the NADPH level in the organoids increased significantly.

[0104] 2) Transcriptomic analysis was performed on organoids treated differently in Experiment 1), and GSEA pathway enrichment was conducted to investigate the changes in energy metabolism of inflammatory organoids under light after co-incubation of the biomaterials provided in this invention with inflammatory organoids. See the results for details. Figure 8 .from Figure 8 As can be seen from the figure, compared with the no-light group, the oxidative phosphorylation pathway was significantly upregulated in the light-illuminated group (positive values ​​of the curves in the figure represent upregulation, and negative values ​​represent downregulation; the larger the absolute value of the curve, the greater the degree of upregulation or downregulation).

[0105] 3) Organoids treated differently in Experiment 1) were cultured at 37℃ for another 2 days. The gene expression level of the inflammatory cytokine IL-6 in the organoids under different treatments was detected by q-PCR. See details for the results. Figure 9As can be seen from the figure, when the inflamed organoids were co-incubated with the biomaterials of this invention and subjected to light treatment, the expression level of the inflammatory factor IL-6 in the organoids was significantly lower than that in the organoids that were not subjected to light treatment, indicating that this treatment method can effectively improve the inflammation of the organoids.

[0106] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

[0107] References:

[0108] 1. Chen, P. et al. A plant-derived natural photosynthetic system for improving cell anabolism. Nature 612, 546–554 (2022).

[0109] 2.H.Chong.et al.Conjugated polymer nanoparticles for light-activatedanticancer and antibacterial activity with imaging capability.Langmuir 28,2091–2098(2012).

[0110] 3. Nie, D. et al. Cancer-cell-membrane-coated nanoparticles with a yolk–shell structure augment cancer chemotherapy. Nano Lett. 20, 936–946 (2020).

Claims

1. A bioactive material having an anti-inflammatory function, characterized by, The bioactive material includes a conjugated compound and a photosynthetic material connected by electrostatic and hydrophobic interactions, wherein the conjugated compound has the effect of promoting the spectral absorption capacity of the photosynthetic material.

2. The bioactive material of claim 1, wherein, The compound is selected from at least one of boron dipyrrole methylene and its water-soluble derivatives; Preferably, the compound has the structure shown in formula (I): In formula (I), a is any integer from 1 to 100, b is any integer from 1 to 100, n is any integer from 1 to 100, and X is F, Cl, Br, or I; And / or, the photosynthetic material is selected from at least one of algae, chloroplasts and thylakoids, or the photosynthetic material is prepared from at least one of algae, chloroplasts and thylakoids.

3. The bioactive material of claim 1 or 2, wherein, In the bioactive material, the concentration of the compound is 1-20 μM relative to 10 μg / mL of the photosynthetic material.

4. A biomaterial, characterized by, The biomaterial includes a cell membrane and a bioactive material loaded on the cell membrane, wherein the bioactive material is the bioactive material according to any one of claims 1-3.

5. The biomaterial according to claim 4, wherein, The cell membrane is selected from cell membranes derived from mammalian cells, preferably human cell membranes; Preferably, the cell membrane is selected from at least one of cancer cell membranes, stem cell membranes, and immune cell membranes; More preferably, the cell membrane is selected from at least one of human breast cancer cell membrane, human liver cancer cell membrane, human pluripotent stem cell membrane, human mesenchymal stem cell membrane, and human macrophage cell membrane.

6. The use of the bioactive material according to any one of claims 1-3, or the use of the biomaterial according to claim 4 or 5 in improving intracellular energy imbalance, particularly in increasing the content of intracellular adenosine triphosphate and / or nicotinamide adenine dinucleotide phosphate.

7. The bioactive material according to any one of claims 1-3, or the biomaterial according to claim 4 or 5, in the preparation of a medicament for treating inflammation.

8. A method for improving inflammation in cell cultures in vitro, characterized in that, The method includes (1) Introducing the bioactive material of any one of claims 1-3 into a cell culture with inflammatory characteristics, or contacting the biomaterial of claim 4 or 5 with a cell culture with inflammatory characteristics; (2) Treat the cell culture with light.

9. The method according to claim 8, wherein, The cell culture is selected from cells and / or organoids cultured in vitro; Preferably, the organoids are selected from at least one of brain organoids, heart organoids, liver organoids, pancreatic organoids, and intestinal organoids.

10. The method according to claim 8, wherein, The conditions for the light treatment include: light intensity of 1-50 mW / cm². 2 Preferred value: 1-25mW / cm 2 Irradiation time: 5-60 min, preferably 10-30 min.

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