Chiral manganese dioxide nanoparticle and preparation method therefor and application thereof

Abstract

The present invention relates to the technical field of material chemistry, and relates to a chiral manganese dioxide nanoparticle and a preparation method therefor and an application thereof. In the present invention, the chiral manganese dioxide nanoparticle having good biocompatibility is prepared by taking D-gluconic acid as a ligand. The prepared chiral manganese dioxide nanoparticle of the present invention has a strong circular dichroism signal in a visible light region, so that interference of signals in a small molecule ultraviolet region in an organism can be avoided; and by means of the redox reaction with ROS, the change in the circular dichroism signal intensity of the chiral manganese dioxide nanoparticle presents a good linear relationship with the concentration of ROS, so that the quantitative detection of ROS is achieved. The chiral manganese dioxide nanoparticle prepared in the present invention can effectively remove ROS in aged skin, increase dermis thickness and collagen proportion, and reduce the oxidative stress level in skin tissue, and is beneficial to delaying skin aging.

Description

Chiral manganese dioxide nanoparticles and preparation method and application thereof Technical Field

[0001] The present invention relates to the technical field of material chemistry, and in particular to chiral manganese dioxide nanoparticles and a preparation method and application thereof. Background Art

[0002] ROS are products of aerobic metabolism in the body, including superoxide, hydroxyl radicals, hydrogen peroxide, hypochlorous acid, etc. Maintaining the dynamic balance of ROS plays an important role in intracellular signal transduction and regulation, gene expression, and body homeostasis. It has been reported that oxidative damage caused by excessive accumulation of ROS can lead to DNA damage, lipid peroxidation, and disruption of protein structure and function, leading to aging and aging-related diseases. The most intuitive manifestation of aging is on the skin, with obvious characteristics such as sagging skin, increased wrinkles, decreased collagen, and thinning of the epidermis and dermis. In addition, skin aging is also accompanied by a decrease in its barrier and defense functions, leading to an increased incidence of related diseases.

[0003] Traditional methods for ROS detection and analysis include chemiluminescence, fluorescent probes, and electron paramagnetic resonance. However, these methods are limited in their application due to poor biocompatibility, low sensitivity, and interference from the autofluorescence of biological substrates. In recent years, with the development and advancement of nanotechnology, chiral nanomaterials have been widely used in bioassays, bioimaging, disease diagnosis, and treatment. Therefore, the preparation of a novel chiral manganese dioxide nanoparticle, which utilizes the reversible redox reaction between manganese particles and ROS to quantitatively detect and effectively remove excess ROS accumulation in aging skin, has important research implications for alleviating age-related diseases, particularly combating skin aging.

[0004] Summary of the Invention

[0005] To address the shortcomings of existing detection technologies, the present invention provides chiral manganese dioxide nanoparticles, their preparation method, and applications. Specifically, this method, specifically a biocompatible chiral manganese dioxide preparation method, utilizes circular dichroism (CD) signal changes in the visible light region to enable real-time quantitative detection of ROS in living cells, successfully avoiding interference from UV CD signals from intracellular molecules. Furthermore, the chiral manganese dioxide nanoparticles undergo a reversible redox reaction with ROS, effectively removing excess ROS accumulation in aging skin and alleviating skin aging.

[0006] The present invention is achieved through the following technical solutions:

[0007] The first object of the present invention is to provide a method for preparing chiral manganese dioxide nanoparticles, comprising the following steps:

[0008] A manganese source and chiral gluconic acid are mixed in a solvent, and the pH is adjusted to alkaline to obtain the chiral manganese dioxide nanoparticles.

[0009] In one embodiment of the present invention, one or more of the following conditions are met:

[0010] (1) The chiral gluconic acid is D-gluconic acid or L-gluconic acid;

[0011] (2) the manganese source is selected from manganese chloride and / or manganese nitrate;

[0012] (3) The solvent is selected from one or more of ethylene glycol, ethanol and polyethylene glycol.

[0013] The second object of the present invention is to provide chiral manganese dioxide nanoparticles prepared by the preparation method.

[0014] In one embodiment of the present invention, one or both of the following conditions are met:

[0015] (a) The particle size of the chiral manganese dioxide nanoparticles is 3 nm to 20 nm, preferably 3 nm to 6 nm;

[0016] (b) The circular dichroism signal of the chiral manganese dioxide particles is between 400 nm and 700 nm.

[0017] In one embodiment of the present invention, the pH regulator is sodium hydroxide.

[0018] The third object of the present invention is to provide the application of the chiral manganese dioxide nanoparticles in detecting ROS.

[0019] In one embodiment of the present invention, the circular dichroism signal of the chiral manganese dioxide nanoparticles used for ROS detection is at 553 nm.

[0020] In one embodiment of the present invention, the concentration of ROS is 0.01 μM-100 μM; preferably 0.01 μM-10 μM.

[0021] In one embodiment of the present invention, the reaction mechanism of the chiral manganese dioxide nanoparticles with ROS is that tetravalent manganese is reduced to divalent manganese and oxygen; and divalent manganese is further oxidized to tetravalent manganese and water.

[0022] The fourth object of the present invention is to provide a composition comprising the chiral manganese dioxide nanoparticles.

[0023] The fifth object of the present invention is to provide the use of the chiral manganese dioxide nanoparticles or the composition in the preparation of anti-aging skin care products; effectively removing excessive ROS accumulation in aging skin.

[0024] In one embodiment of the present invention, the skin care product is a lotion, cream, facial mask, essence, skin care water, facial cleanser or gel.

[0025] The sixth object of the present invention is to provide the use of the chiral manganese dioxide nanoparticles or the composition in the preparation of anti-aging drugs or health products.

[0026] In one embodiment of the present invention, the chiral manganese dioxide nanoparticles are administered by intraperitoneal injection.

[0027] In one embodiment of the present invention, the dosage of the chiral manganese dioxide nanoparticles is 40 mg / kg-60 mg / kg.

[0028] In one embodiment of the present invention, the injection frequency of the chiral manganese dioxide is once every 1-3 days for 1-2 consecutive months.

[0029] The above technical solution of the present invention has the following advantages over the prior art:

[0030] The present invention provides chiral manganese dioxide nanoparticles and a preparation method and application thereof. The chiral manganese dioxide nanoparticles prepared by the present invention have strong circular dichroism signals in the visible light region, which can avoid interference from ultraviolet region signals of small molecules in the body.

[0031] The chiral manganese dioxide nanoparticles prepared in the present invention undergo a redox reaction with ROS, and the resulting circular dichroism signal intensity change shows a good linear relationship with the ROS concentration, thereby achieving quantitative detection of ROS.

[0032] The chiral manganese dioxide nanoparticles prepared in the present invention can effectively remove ROS in aging skin, increase dermal thickness and collagen ratio, reduce the level of oxidative stress in skin tissue, and help delay skin aging. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below based on specific embodiments of the present invention in conjunction with the accompanying drawings, wherein

[0034] FIG1 is a transmission electron microscope image of chiral manganese dioxide nanoparticles in Example 1 of the present invention;

[0035] FIG2 is a circular dichroism spectrum of chiral manganese dioxide nanoparticles in Example 1 of the present invention;

[0036] FIG3 is a graph showing the circular dichroism spectrum of chiral manganese dioxide nanoparticles according to Example 2 of the present invention as a function of hydrogen peroxide concentration;

[0037] FIG4 is a diagram showing the reaction mechanism of chiral manganese dioxide nanoparticles scavenging active oxygen in Example 3 of the present invention;

[0038] FIG5 is a diagram showing how chiral manganese dioxide nanoparticles improve the skin condition of aging mice in Example 4 of the present invention;

[0039] FIG6 is a statistical diagram showing that chiral manganese dioxide reduces the oxidative stress level in skin tissue and increases the expression of oxidoreductases in Example 5 of the present invention. DETAILED DESCRIPTION

[0040] The present invention will be further described below with reference to the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it. However, the embodiments are not intended to limit the present invention.

[0041] Example 1 Preparation method of chiral manganese dioxide nanoparticles.

[0042] Chiral MnO2 nanoparticles were synthesized using D-gluconic acid as a ligand: 50 mL of ethylene glycol solution, 10 mL of 100 mmol / L manganese chloride solution, and 20 mL of 100 mmol / L D-gluconic acid solution were uniformly mixed at room temperature and stirred for 10 minutes. Then, 20 mL of 1 mmol / L sodium hydroxide solution was added and stirred at room temperature for 6 hours, until the solution eventually turned brownish red. The obtained product was added to anhydrous ethanol at a volume ratio of 1:3 to obtain a milky white turbid liquid. The solution was then centrifuged at 8000 rpm / min for 10 minutes. The precipitate, which was the chiral manganese dioxide nanoparticles, was resuspended in ultrapure water for characterization and subsequent experiments.

[0043] From the transmission electron microscopy characterization in Figure 1, it can be seen that the prepared chiral particles have good dispersion and uniform particle size, with a diameter of about 5 nm. At the same time, from the circular dichroism spectrum in Figure 2, it can be seen that the MnO2 nanoparticles have a strong chiral signal, and the circular dichroism spectrum shows two obvious peaks at 440 nm and 553 nm.

[0044] Example 2 Quantitative detection method of ROS using chiral manganese dioxide nanoparticles.

[0045] In an in vitro experiment, different concentrations of hydrogen peroxide were added to a solution of chiral manganese dioxide nanoparticles at the same concentration. After a 30-second reaction, the circular dichroism signal was analyzed. The results showed that the circular dichroism signal decreased linearly with increasing hydrogen peroxide concentration (Figure 3). The intensity of the circular dichroism signal at 553 nm can be used to quantitatively measure the hydrogen peroxide concentration in the system.

[0046] Example 3 Reaction mechanism between chiral manganese dioxide nanoparticles and ROS.

[0047] X-ray photoelectron spectroscopy was used to measure the valence state of manganese in the solution before and after the reaction in Example 2. There was no significant change in divalent manganese and tetravalent manganese before and after the reaction. In the presence of hydrogen peroxide, tetravalent manganese was reduced to divalent manganese and oxygen. Furthermore, divalent manganese further reacted with hydrogen peroxide, becoming dioxide and water (Figure 4).

[0048] Example 4 Chiral manganese dioxide improves the thickness and collagen ratio of mouse dermal tissue.

[0049] Wild-type mice were randomly divided into three groups, with three mice in each group. One group was subcutaneously injected with 0.2 mL of normal saline as a negative control, and one group was injected with 0.2 mL of D-galactose (200 mg / kg) once a day for 8 weeks to induce a skin aging model; one group was injected with 0.2 mL of D-galactose (200 mg / kg) once a day for 8 weeks, and from the fifth week, 0.2 mL of chiral manganese dioxide nanoparticles were injected again 6 hours after the daily injection of D-galactose at a dose of 50 mg / kg. After 8 weeks, all mice were killed and skin tissues were collected to detect the thickness of the mouse dermis and the proportion of collagen. The test results in Figure 5 show that the dermis thickness and collagen ratio of the skin-aging mice injected with chiral manganese dioxide nanoparticles increased significantly.

[0050] Example 5 Chiral manganese dioxide reduces the oxidative stress level in skin tissue and increases the activity of oxidoreductase.

[0051] The skin tissue samples obtained in Example 4 were tested using a kit to detect the oxidative stress level and antioxidant enzyme activity in the skin tissue. As shown in Figure 6, the oxidative stress level in the skin tissue of mice injected with chiral manganese dioxide nanoparticles was reduced, and the antioxidant enzyme activity was increased.

[0052] In this example, the hydrogen peroxide kit was purchased from Beyotime Biotechnology Co., Ltd. with the item number S0038; the lipid oxidation kit was purchased from Beyotime Biotechnology Co., Ltd. with the item number S0131S; the glutathione kit was purchased from Beyotime Biotechnology Co., Ltd. with the item number S0052; the glutathione peroxidase kit was purchased from Beyotime Biotechnology Co., Ltd. with the item number S0056; and the catalase kit was purchased from Beyotime Biotechnology Co., Ltd. with the item number S0051.

[0053] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will appreciate that other variations or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A method for preparing chiral manganese dioxide nanoparticles, characterized in that: The following steps are involved: The manganese source and chiral gluconic acid are mixed in a solvent, and the pH is adjusted to alkaline to obtain the chiral manganese dioxide nanoparticles.

2. The preparation method according to claim 1, characterized in that: One or more of the following conditions are met: (1) The chiral gluconic acid is D-gluconic acid or L-gluconic acid; (2) the manganese source is selected from manganese chloride and / or manganese nitrate; (3) The solvent is selected from one or more of ethylene glycol, ethanol and polyethylene glycol.

3. Chiral manganese dioxide nanoparticles prepared by the preparation method according to any one of claims 1-2.

4. The chiral manganese dioxide nanoparticles according to claim 3, characterized in that: One or both of the following conditions are met: (a) The particle size of the chiral manganese dioxide nanoparticles is 3nm-20nm; (b) The circular dichroism signal of the chiral manganese dioxide particles is between 400nm and 700nm.

5. Use of the chiral manganese dioxide nanoparticles according to claim 3 or 4 in detecting ROS.

6. The use according to claim 5, characterized in that: The concentration of the ROS is 0.01 μM-100 μM.

7. A composition, characterized in that Comprising the chiral manganese dioxide nanoparticles according to claim 3 or 4.

8. Use of the chiral manganese dioxide nanoparticles according to claim 3 or 4 or the composition according to claim 7 in the preparation of anti-aging skin care products.

9. The use according to claim 8, characterized in that: The skin care products are lotions, creams, facial masks, essences, skin care water, facial cleansers or gels.

10. Use of the chiral manganese dioxide nanoparticles according to claim 3 or 4 or the composition according to claim 7 in the preparation of anti-aging drugs or health products.

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