CN-121971608-A - Bionic sound-sensitive nano-drug and preparation method and application thereof

Abstract

The invention relates to the technical field of medicines and provides a bionic sound-sensitive nano-drug which is formed by coating nano-particles with macrophage membranes, and the preparation method comprises the following steps of S1, respectively dissolving sound-sensitive agents and epigenetic regulation drugs in organic solvents to obtain sound-sensitive agent solutions and drug solutions with consistent concentrations, uniformly mixing the sound-sensitive agent solutions and the drug solutions, then dripping the sound-sensitive agent solutions and the drug solutions into ultrapure water to prepare nano-particles, S2, fully mixing the macrophage membranes with the nano-particles prepared by the S1, extruding the nano-particles to obtain the multifunctional nano-drug with sound power and epigenetic regulation, and further coating the multifunctional nano-drug with the macrophage membranes by effectively combining the sound-sensitive agents with the epigenetic regulation drugs, so that the purposes of tumor targeted delivery, controllable release and dual immune activation and synergistic treatment of oral squamous cell carcinoma and jaw invasion inhibition can be achieved.

Inventors

• CAO MINGXIN
• YANG ZIJING
• Ju Duan
• LI XINMING
• WANG YUE
• ZHOU NAN

Assignees

• 天津医科大学口腔医院

Dates

Publication Date

20260505

Application Date

20260407

Claims (9)

1. 1. A bionic sound-sensitive nano-drug is characterized by comprising macrophage membrane coated nano-particles, wherein the nano-particles are formed by combining sound-sensitive agents and epigenetic regulation and control drugs through hydrophobic interaction; The preparation method of the bionic sound-sensitive nano-drug comprises the following steps: S1, respectively dissolving an acoustic sensitizer and an epigenetic regulation drug in an organic solvent to obtain an acoustic sensitizer solution and a drug solution with consistent concentration, uniformly mixing the acoustic sensitizer solution and the drug solution, then dripping the mixed solution into ultrapure water, and stirring for a period of time to obtain nanoparticles; S2, adding macrophages into a buffer solution for resuspension, carrying out probe ultrasound in an ice bath environment, centrifuging, collecting supernatant and sediment, resuspension of sediment with the buffer solution, continuing probe ultrasound, centrifuging, collecting supernatant and sediment, repeating the operation for a plurality of times until no obvious cell morphology exists in the lower sediment under a microscope; and S3, fully mixing the macrophage membrane prepared by the S2 and the nano particles prepared by the S1, and extruding to obtain the multifunctional nano medicament with acoustic power and epigenetic regulation.
2. 2. The biomimetic acoustic sensitive nano-drug according to claim 1, wherein the macrophage membrane is reformed in structure by external pressure and coated on the surface of the nanoparticle to form a uniform and stable membrane shell.
3. 3. The biomimetic sound-sensitive nano-drug according to claim 1, wherein the sound-sensitive agent is verteporfin and the epigenetic regulatory drug is tazistat.
4. 4. The biomimetic acoustic drug according to claim 1, wherein the concentration of the acoustic sensitizer solution and drug solution is 15-25mg/mL.
5. 5. The biomimetic acoustic drug nano-composition of claim 1, wherein the acoustic agent solution and the drug solution are mixed in a volume ratio of 1:1-5.
6. 6. The bionic sound-sensitive nano-drug according to claim 1, wherein in S1, the sound-sensitive agent solution and the drug solution are mixed and stirred at 1000-1500rpm for 10-20min, and when the mixture is dropped into ultra-pure water under stirring, the mixture is stirred at 1000-1500rpm for 10-20min.
7. 7. The biomimetic acoustic sensitive nano-drug according to claim 1, wherein in S2, centrifugation is performed at 1000-1500rpm for 10-20min.
8. 8. The bionic acoustic drug according to claim 1, wherein in S3, a nanoliposome extruder is used and repeatedly extruded 10-20 times with a 200-300nm pore size filter.
9. 9. Use of a biomimetic sound-sensitive nano-drug according to any one of claims 1-8 for the preparation of a medicament for the treatment of oral squamous carcinoma while inhibiting jaw invasion.

Description

Bionic sound-sensitive nano-drug and preparation method and application thereof Technical Field The invention relates to the technical field of medicines, in particular to a bionic sound-sensitive nano-drug and a preparation method and application thereof. Background Oral squamous carcinoma is the highest malignant tumor of the oral and maxillofacial area, and the onset is often caused by congenital inheritance, HPV virus infection and long-term smoking and drinking and betel nut chewing. The characteristics are that the invasion is strong, the malignancy is high, the recurrence and transfer are easy, and the invasion of jawbone is easy when the occurrence part is adjacent to jawbone. The existing treatment modes for patients with oral squamous carcinoma mainly comprise operation excision radiotherapy and chemotherapy, targeted treatment and immunotherapy, the operation can excision superficial tumors, but the beauty of the face of the patient is affected, the physiological and psychological effects of the patient are affected, the radiotherapy and chemotherapy toxic and side effects are strong, the prognosis of the patient is poor, and the survival rate of the patient in 5 years is only 40% -50%. Targeting therapy and immunotherapy have become promising therapeutic approaches for oral squamous cell carcinoma in recent years, but single immunotherapy effect is limited due to multi-channel immune imbalance of tumor. Thus, it is particularly necessary to employ a combination therapeutic strategy to achieve synergistic therapeutic effects. Unlike traditional treatment modes, acoustic dynamic therapy (SDT) has the advantages of no wound, difficult tolerance, deep penetrating capacity and the like, and can kill tumor cells through generated active oxygen, release tumor-related antigens and exert vaccine-like effects. At the same time, the immunogenic death of tumor cells induced by it produces a number of lesion-associated molecular patterns, recruiting and activating antigen presenting cells, and initiating T-cell mediated anti-tumor immunity. However, SDT-mediated immune activation is insufficient to inhibit tumor recurrence or metastasis, and studies have shown that synergistic therapeutic effects can be achieved by combined immunotherapy strategies. In oral squamous cell carcinoma, low expression of Major Histocompatibility Complex (MHC) class I molecules is a key factor in tumor immune escape and failure of immunotherapy. The transcription inhibition is mainly related to modification of 27 th lysine trimethylation (H3K 27me 3) of histone H3, and a Zeste gene enhancer homolog (EZH 2) inhibitor, namely, the tazistat can down regulate H3K27me3 expression, weaken the transcription inhibition of MHC-I molecules, further enhance tumor antigen presentation and promote activation of cytotoxic CD8 + T cells. At the same time, the tazistat can promote the expression of the factors epigenetic through inhibiting H3K27me3 modification of the promoter region of the negative regulatory factor gene of the bone fracture, inhibit the differentiation of the bone fracture, and further inhibit the bone invasion process. However, how to avoid leakage of the drug in the process of body transportation, target tumor delivery and controllable release of the drug at the tumor site are key scientific problems to be solved in order to realize synergistic attenuation treatment of oral squamous cell carcinoma. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a bionic sound-sensitive nano-drug and a preparation method and application thereof, which can realize tumor targeted delivery, controllable release and dual immune activation by effectively combining sound-sensitive agents with epigenetic regulation drugs and further coating the sound-sensitive agents with macrophage membranes, thereby achieving the aims of cooperatively treating oral squamous cell carcinoma and inhibiting jawbone invasion. The implementation mode of the invention is realized by the following technical scheme: A bionic sound-sensitive nano-drug is composed of nanoparticles coated by macrophage membranes, wherein the nanoparticles are formed by combining sound-sensitive agents and epigenetic regulation drugs through hydrophobic interaction, and the macrophage membranes are subjected to structure rearrangement through external pressure and coated on the surfaces of the nanoparticles to form uniform and stable membrane shells. A preparation method of a bionic sound-sensitive nano-drug comprises the following steps: S1, respectively dissolving the verteporfin and the tazistat in an organic solvent to respectively obtain a verteporfin solution and a tazistat solution with the concentration of 15-25mg/mL, then mixing the verteporfin solution and the tazistat solution in a volume ratio of 1:1-5, stirring for 10-20min at 1000-1500rpm, taking out the mixed medicine, dripping the mixed medicine into ultrapure water in a stirring st