CN-122005826-A - Tannic acid and aptamer modified copper indium phosphorus sulfur nano-sheet and preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a tannic acid and aptamer modified copper indium phosphorus sulfur nano-sheet, and a preparation method and application thereof. The preparation method comprises the steps of preparing copper indium phosphorus sulfur nano-sheets, connecting tannic acid with the copper indium phosphorus sulfur nano-sheets through Fenton reaction to obtain tannic acid modified copper indium phosphorus sulfur nano-sheets, and finally jointly modifying amino modified aptamer and tannic acid on the copper indium phosphorus sulfur nano-sheets through reaction to obtain tannic acid and the aptamer modified copper indium phosphorus sulfur nano-sheets. The tannic acid and aptamer modified copper indium phosphorus sulfur nano-sheet can simultaneously have the binding capacity of dsDNA and NETs/EETs, the RONS clearing capacity and the antibacterial capacity, and has excellent regulation effect on deregulated inflammation in a secretory otitis media rat model so as to improve hearing loss.

Inventors

• TU ZHAOXU
• WEN WEIPING
• LIU MING
• XIAO YONGQIANG

Assignees

• 中山大学附属第六医院

Dates

Publication Date

20260512

Application Date

20250623

Claims (10)

1. 1. The preparation method of the tannic acid and aptamer modified copper indium phosphorus sulfur nano-sheet is characterized by comprising the following steps of: S1, preparing a crude copper indium phosphorus sulfur nano-sheet product by a lithium ion intercalation method, centrifuging the crude product to remove impurities, collecting a precipitate, continuously centrifuging the precipitate, collecting a supernatant, and dialyzing to obtain the copper indium phosphorus sulfur nano-sheet; S2, connecting tannic acid with the copper indium phosphorus sulfur nano-sheet through Fenton reaction to obtain the tannic acid modified copper indium phosphorus sulfur nano-sheet; s3, reacting the amino-modified aptamer with a tannic acid-modified copper indium phosphorus sulfur nano-sheet to prepare tannic acid and the aptamer-modified copper indium phosphorus sulfur nano-sheet; The mass ratio of the tannic acid to the copper indium phosphorus sulfur nano-sheet is 1:0.5-4; The amino-modified aptamer is at least one of an amino-modified EPX aptamer and an amino-modified histone H4 aptamer.
2. 2. The preparation method of claim 1, wherein the mass ratio of tannic acid to copper indium phosphorus sulfur nano-sheets is 1:1-3.
3. 3. The method according to claim 1 or 2, wherein the precipitate is further centrifuged at a rotational speed of at least 10000rpm, and the supernatant is collected.
4. 4. The preparation method of the copper indium phosphorus sulfur nano-sheet according to claim 1, wherein in the step S1, the operation of preparing the copper indium phosphorus sulfur nano-sheet crude product by adopting a lithium ion intercalation method is that raw materials of copper indium phosphorus sulfur, lithium salt and a solvent are mixed and stirred for reaction under a protective gas atmosphere, so that the copper indium phosphorus sulfur nano-sheet crude product is prepared.
5. 5. The preparation method according to claim 1, wherein in the step S2, the step of connecting the tannic acid with the copper indium phosphorus sulfur nano-sheets comprises the steps of mixing the tannic acid with the copper indium phosphorus sulfur nano-sheets under alkaline conditions for reaction and dialyzing to obtain the tannic acid modified copper indium phosphorus sulfur nano-sheets.
6. 6. The method according to claim 5, wherein in the step S1, the dialysis has a molecular weight cut-off of 3000 to 5000; and/or in said step S2, the dialysis has a molecular weight cut-off of 9000-11000.
7. 7. The method of claim 1, wherein the amino modified EPX aptamer has a sequence of 5'to 3' H 2 N-ATGCCATCCT ACCAACGGTC GATGGATGAG TAATACAGGC CGGATGGGTA CAGTCG and the amino modified histone H4 aptamer has a sequence of 5'to 3' H 2 N-AGACG TAAGT TAATT GGACT TGGTC GTGTG CGGCA CAGCG ATTGA AAT.
8. 8. The method of claim 1 or 7, wherein the amino modified aptamer is an amino modified histone H4 aptamer.
9. 9. The tannic acid and aptamer modified copper indium phosphorus sulfur nanoplatelets prepared by the preparation method of any one of claims 1-8.
10. 10. Use of tannic acid and aptamer modified copper indium phosphorus sulfur nanoplatelets as defined in claim 9 for the preparation of a medicament for the prevention and treatment of secretory otitis media, for the removal of active oxygen and/or for bacteriostasis.

Description

Tannic acid and aptamer modified copper indium phosphorus sulfur nano-sheet and preparation method and application thereof Technical Field The invention belongs to the technical field of biomedical materials, and particularly relates to a tannic acid and aptamer modified copper indium phosphorus sulfur nano-sheet, and a preparation method and application thereof. Background Neutrophil extracellular traps (fets) and Eosinophil Extracellular Traps (EETs) are large extracellular reticular chromatin structures released by stimulated neutrophils and eosinophils. Despite the control of pathogen infection, excessive NET/EET can also lead to inflammatory disorders. Recent studies have emphasized the presence of NET/EET in a variety of inflammation-related disorders, which are associated with exacerbation of inflammatory responses. Persistent secretory otitis media can lead to bacterial infections and chronic otitis media, and surgical and non-surgical treatments often cause complications or are ineffective. More serious otogenic complications, such as mastoiditis, labyrinthine, venous sinus thrombosis or intracranial complications, may also occur if not properly treated, possibly leading to fatal consequences. Recent reports also underscore the key role of NET/EETs in the onset and progression of otitis media, indicating that they are potential therapeutic targets. It is widely recognized that double stranded DNA (dsDNA) in NETs/EETs can be recognized by Pattern Recognition Receptors (PRRs) in immune cells. This recognition triggers an intracellular immune signaling cascade, inducing the release of pro-inflammatory cytokines. In addition, extracellular Traps (ET) have cytotoxic effects on healthy cells and tissues, promoting local inflammation and tissue damage. Accumulation of NET/EETs in blood and tissue can trigger systemic and local inflammatory responses, which are associated with a range of inflammatory and infectious diseases. Of particular interest, DNA molecules are key structural components of extracellular polymers in bacterial biofilms, making ET an attractive target for controlling biofilm-related infections. Furthermore, EETs are closely related to allergen-triggered type 2 immune cascades, playing a key role in many allergic inflammatory diseases. In view of this, therapeutic strategies directed to ET, particularly those involving neutrophil and eosinophil activation, migration and stimulation, are promising for the treatment of many inflammation-related disorders. Although NET/EET removal is promising in the treatment of ET related inflammatory diseases, there is currently no therapeutic strategy that is clinically targeted. Secretory otitis media (secretory otitis media) is a common ear disorder, mainly manifested by effusion of the middle ear and hearing loss, the tympanic membrane often being intact. The causes of secretory otitis media include (1) eustachian tube dysfunction, which is one of the main causes of secretory otitis media, including eustachian tube obstruction, eustachian tube cleaning and defense dysfunction, etc., such as adenoid hypertrophy, chronic sinusitis, nasopharyngeal carcinoma, etc. The conditions can cause poor ventilation function of eustachian tubes, negative pressure is formed by gradually absorbing gas in the middle ear, thus causing swelling of mucous membrane of the middle ear and increase of capillary permeability, and finally causing accumulation of liquid in the middle ear, (2) after upper respiratory tract infection, pathogens such as bacteria or viruses can enter the middle ear through the eustachian tubes, and cause inflammatory reaction of mucous membrane of the middle ear, so that mucous membrane edema and secretion are increased, and the eustachian tube lumen is blocked, thus causing negative pressure and effusion of the middle ear, (3) the immune system of the organism generates abnormal immune reaction to antigen entering the middle ear, and causes inflammation and edema of mucous membrane of the middle ear, thereby affecting the function of eustachian tubes and causing effusion of the middle ear. Two-dimensional nanoplatelets have been used as a study of novel therapeutic agents for related inflammation as functionalized biomaterials with good cfDNA clearance. For example, patent publication No. CN117285718A discloses aminopolyglycerol and modified black phosphorus nanoplatelets thereof, which have better dsDNA clearance ability, and show inflammation targeting in nasal cavity, thereby playing better role in regulating nasal inflammation. However, patients with secretory otitis media cannot be treated by single dsDNA clearance, elevated reactive oxygen species and reactive nitrogen species (ROS/RNS) and bacterial infections at the inflammatory sites in the patient still cause sustained damage to the airway epithelium, leading to the sustained progression of secretory otitis media. Disclosure of Invention Aiming at the prior art problems, the primary aim o