Search

CN-122005850-A - Supermolecule nano enzyme antagonist with multiple-effect synergistic effect and preparation method and application thereof

CN122005850ACN 122005850 ACN122005850 ACN 122005850ACN-122005850-A

Abstract

The invention discloses a supermolecule nano enzyme antagonist with multiple-effect synergistic effect, and a preparation method and application thereof, and belongs to the technical field of biological nano engineering materials. The invention drives the formation of nano-assembly through Mannich reaction, amino on aminoglycoside compound and EGCG ring A form benzoxazine structure, while EGCG has polyphenol part with metal ion chelating ability, then selenium ion is led into reaction system, and the selenium ion is adsorbed onto nano-assembly surface, finally selenium ion is reduced to simple substance selenium under reduction of ascorbic acid, and nano-selenium particles are formed in situ due to nano-constraint effect, thus constructing supermolecule nano-enzyme antagonist with high cfDNA capturing and ROS scavenging ability.

Inventors

  • CHEN LEI
  • XIAO JIAN
  • GAO QI

Assignees

  • 温州医科大学

Dates

Publication Date
20260512
Application Date
20260227

Claims (10)

  1. 1. The preparation method of the supermolecule nano enzyme antagonist with multiple-effect synergistic effect is characterized by comprising the following steps: (1) Mixing an epigallocatechin gallate aqueous solution and a formaldehyde aqueous solution, reacting, and then dropwise adding an aminoglycoside compound aqueous solution to perform a Mannich reaction to obtain a Mannich nano-assembly; (2) Dispersing the Mannich nano-assembly in water, adding sodium selenite aqueous solution, stirring uniformly, and then adding ascorbic acid solution for reduction reaction to obtain the supermolecule nano-enzyme antagonist.
  2. 2. The preparation method of the epigallocatechin gallate aqueous solution is characterized in that in the step (1), the concentration of the epigallocatechin gallate aqueous solution is 5-20 mmol/L, the concentration of the formaldehyde aqueous solution is 12.3mmol/L, and the volume ratio of the epigallocatechin gallate aqueous solution to the formaldehyde aqueous solution is 200:1-20.
  3. 3. The method according to claim 1, wherein in the step (1), the reaction time is 5 to 30 minutes.
  4. 4. The preparation method of claim 1, wherein in the step (1), the aminoglycoside compound in the aqueous aminoglycoside compound solution is at least one selected from hygromycin, netilmicin, kanamycin, tobramycin and neomycin, the concentration of the aqueous aminoglycoside compound solution is 5-20 mmol/L, and the volume ratio of the aqueous aminoglycoside compound solution to the aqueous epigallocatechin gallate solution is 1:1.
  5. 5. The preparation method of claim 1, wherein in the step (1), the dropping speed is 5-10 s/drop, and the Mannich reaction time after the dropping is finished is 2-12 h.
  6. 6. The preparation method of claim 1, wherein in the step (2), the concentration of the sodium selenite aqueous solution is 10-100 mmol/L, and the volume ratio of the sodium selenite aqueous solution to the Mannich nano-assembly is 1:5.
  7. 7. The method according to claim 1, wherein in the step (2), the concentration of the ascorbic acid solution is 40mmol/L, and the volume ratio of the ascorbic acid solution to the Mannich nano-assembly is 2:5.
  8. 8. The method according to claim 1, wherein in the step (2), the reduction reaction time is 12 to 24 hours.
  9. 9. A multi-effect synergistic supramolecular nanoenzyme antagonist, characterized in that it is prepared by the preparation method according to any one of claims 1-8.
  10. 10. Use of a pleiotropic synergistic supramolecular nanoenzyme antagonist of claim 9 in the preparation of a medicament for alleviating psoriasis.

Description

Supermolecule nano enzyme antagonist with multiple-effect synergistic effect and preparation method and application thereof Technical Field The invention belongs to the technical field of biological nano engineering materials, and particularly relates to a supermolecule nano enzyme antagonist with multiple-effect synergistic effect, and a preparation method and application thereof. Background Psoriasis is a common inflammatory skin disease, which is mainly characterized by thickening of the epidermis of the skin, erythema plaques and covering silvery white, hardened scales, and about 2-3% of the population worldwide suffers from this disease. Currently, the clinical treatment of psoriasis is largely dependent on the drug controlling inflammatory response, including glucocorticoids, vitamin D derivatives, targeted biological agents, folic acid antagonists, calcineurin inhibitors, and the like. However, prolonged use of these drugs may lead to immunosuppression, increasing the risk of infection and skin cancer in the patient. Therefore, there is an urgent need to develop new drug replacement therapies to effectively alleviate the psoriasis inflammatory response and mitigate its side effects. In recent years, researchers have developed a range of cationic nanomaterials that effect modulation of the inflammatory response by scavenging nucleic acids released from dead cells. Thus, designing cationic nanomaterials to capture cfDNA to block inflammatory signaling pathways is a potential psoriasis treatment strategy. For example, chen Yongming team （Z. Liu, Y. Wang, Y. Zhang, et al. Biguanide chitosan microneedles with cell-free DNA scavenging ability for psoriasis therapy [J]. Bioactive Materials: 2024, 33: 497-505.） designs and synthesizes a series of poly (2- (dimethylamino) ethyl methacrylate) (PDMA) grafted hairy silicon particles (cSPs) which are used as cfDNA capturing agents, can be used for removing cfDNA in dermis, and has good treatment effect on psoriasis. On the other hand, reactive Oxygen Species (ROS), such as superoxide anions (.o 2-) and hydrogen peroxide (H 2O2), are capable of activating the mTOR-NF- κb pathway in keratinocytes and stimulating the release of inflammatory factors, thereby initiating and maintaining the progression of psoriasis. In psoriatic patients, deregulation of the oxidation/reduction balance can lead to excessive accumulation of ROS, which in turn increases oxidative damage to keratinocytes, which after death release more cfDNA, forming an inflammatory vicious cycle. Thus, scavenging excessive accumulation of ROS at the site of inflammation, and reducing the level of oxidative stress in skin tissue are considered as a potential strategy for the treatment of psoriasis. For example, a gel microneedle patch is developed by the university of Huazhong science and technology Zhu Jintao/Liu Yijing team （D. Bi, F. Qu, W. Xiao, et al. Reactive oxygen species-responsive gel-based microneedle patches for prolonged and intelligent psoriasis management [J]. ACS Nano: 2023, 17 (5): 4346-4357）, and can simultaneously deliver an anti-cell proliferation drug of Methotrexate (MTX) and an ROS scavenging drug of epigallocatechin gallate (EGCG) for the combined treatment of psoriasis, wherein the release of MTX can inhibit the proliferation of keratinocytes, and the sustained release of EGCG can scavenge intracellular ROS and inhibit the activation of NF- κB, so that the anti-inflammatory effect is realized. The human body itself has a natural antioxidant system mainly composed of antioxidant enzymes such as Catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), which scavenge intracellular ROS by catalytic reactions to maintain oxidative/reductive homeostasis. However, studies have found that these antioxidant enzymes are under-expressed in the skin tissue of psoriasis patients, resulting in the inability of ROS accumulated in the skin to be cleared in time, leading to exacerbation of the condition. Therefore, the nano material with the antioxidant enzyme-like activity is used for removing excessive ROS in the skin of psoriasis, and restoring the oxidation/reduction steady state of the skin, so that the nano material is a potential treatment scheme. Currently, cfDNA capture strategies based on cationic nanomaterials and ROS scavenging strategies based on antioxidant enzyme-like active nanomaterials both show a certain efficacy in alleviating the symptoms of psoriasis, but nanomaterials with a single mechanism of action still face challenges of efficacy limitation due to the complex microenvironment of psoriasis inflammation. Therefore, how to construct a nano hybrid material with both high cfDNA capturing and ROS scavenging capabilities becomes a technical problem to be solved in the art. Disclosure of Invention In order to solve the technical problems, the invention provides a supermolecule nano enzyme antagonist with multiple-effect synergistic effect, and a preparation