CN-122005495-A - Grapefruit extracellular vesicle modified bionic phase change nanoparticle and preparation method and application thereof

Abstract

The invention discloses a bionic phase-change nanoparticle EV@NP modified by an extracellular vesicle of a grapefruit, which is obtained by compounding the phase-change nanoparticle NP with the extracellular vesicle GFEV of the grapefruit, and relates to the technical field of nano drug delivery systems and intracranial nerve disease treatment. The phase change nano particles provided by the invention can be coated by the membrane through the grape fruit-derived extracellular vesicles to prepare the bionic phase change nano drug carrier, and the bionic phase change nano drug carrier is used for in-vivo drug delivery, and the phase change nano drug carrier directly acts on nerve cells through carrying drugs or functional molecules, so that a new treatment scheme is provided for the effective treatment of intracranial nervous system diseases such as glioma and the like.

Inventors

• SUN CHUNYANG
• HU WEIJIE
• ZHAO FENGNIAN

Assignees

• 天津医科大学总医院

Dates

Publication Date

20260512

Application Date

20260309

Claims (9)

1. 1. The bionic phase change nano particle modified by the grape fruit extracellular vesicles is named EV@NP, the bionic phase change nano particle is obtained by compounding phase change nano particle NP carrying a sound sensitive agent with grape fruit extracellular vesicles GFEV, the NP is obtained by compounding disulfide bond bridged polyphosphate SS-PPE, perfluoro-n-pentane PFP and hematoporphyrin monomethyl ether HMME, the surface of the EV@NP is provided with a membranous structure, and GFEV is coated on the surface of the NP, and the diameter of the EV@NP is 110-150nm.
2. 2. The method for preparing the bionic phase change nanoparticle according to claim 1, comprising the steps of preparing NP, preparing GFEV and preparing EV@NP.
3. 3. The preparation method of claim 2, wherein the NP is prepared by dissolving SS-PPE, PFP and HMME in a mass ratio of 8:2:1 in anhydrous chloroform simultaneously, uniformly mixing with water, emulsifying by an ultrasonic cytoclasis instrument, and performing rotary evaporation under reduced pressure.
4. 4. The method of claim 2, wherein GFEV is prepared by squeezing grapefruit pulp, subjecting to four differential centrifugation at 4 ℃ under conditions of 500 g,0.16 h;2000 g,0.33 h;5000 g,0.5 h; 10000 g, 1h each time collecting supernatant, followed by an ultracentrifugation of 100000 g for a period of 2h, collecting the precipitate after centrifugation and performing density gradient centrifugation using a sucrose gradient system, the sucrose concentration being 8%, 30%, 45% and 60% in order from low to high, the centrifugation temperature being 4 ℃, the centrifugal force being 150000 g, the centrifugation duration being 2h, and finally collecting the product between 30% and 45% concentration gradients.
5. 5. The preparation method of claim 2, wherein the preparation of ev@np comprises uniformly mixing NP and GFEV in water in a mass ratio of 1:1, treating 2: 2 min with an ultrasonic cleaner, performing ten continuous extrusion treatments with a liposome extruder with a pore size of 400 nm, centrifuging to collect precipitate at a centrifugal force of 3000 g for a centrifugal time of 0.25 h, and collecting precipitate to obtain the grapefruit extracellular vesicle-modified bionic phase change nanoparticle ev@np.
6. 6. Use of the grapefruit extracellular vesicle modified biomimetic phase-change nanoparticle of claim 1 or obtained by the preparation method of any one of claims 2-5 for the production of ROS.
7. 7. Use of the grapefruit extracellular vesicle modified biomimetic phase-change nanoparticle of claim 1 or obtained by the preparation method of any one of claims 2-5 in the preparation of a medicament for killing glioma cells.
8. 8. Use of the grapefruit extracellular vesicle modified biomimetic phase change nanoparticle of claim 1 or obtained by the preparation method of any one of claims 2-5 in the preparation of a medicament for modulating the iron death effect of glioma cells.
9. 9. Use of the grapefruit extracellular vesicle modified biomimetic phase-change nanoparticle of claim 1 or obtained by the preparation method of any one of claims 2-5 in the preparation of a medicament for treating neurological diseases.

Description

Grapefruit extracellular vesicle modified bionic phase change nanoparticle and preparation method and application thereof Technical Field The invention relates to the technical field of nano drug delivery systems and intracranial nerve disease treatment, in particular to a drug delivery system for targeting malignant glioma, and especially relates to a bionic phase change nano particle modified by an extracellular vesicle of a grapefruit and a preparation method thereof, thereby being further applied to the field of glioma treatment. Background Gliomas are the most invasive and fatal tumors in the central nervous system, with a high degree of wettability, invasiveness, heterogeneity and recurrent. In addition to surgical treatment, chemotherapy is a routine clinical treatment for gliomas. However, due to the presence of physiological Blood Brain Barrier (BBB) and blood Brain Tumor Barrier (BTB), chemotherapeutic agents tend to have difficulty effectively entering glioma cells, limiting their therapeutic efficacy. To address this challenge, researchers have explored a variety of nanoparticle drug delivery systems aimed at improving the efficacy of glioma treatment by bypassing the BBB/BTB. Extracellular Vesicles (EVs) are distributed almost universally in all body fluids. With the continuous development of nanotechnology, EVs secreted by plants have become a research hotspot in recent years due to their low-cost and abundant raw material sources and good regeneration capability. EVs biogenesis processes typically include the vacuolar pathway, the multivesicular pathway, and the extracellular positive organelle pathway. As natural nanoparticles, plant-derived Extracellular Vesicles (EVs) have been demonstrated to be able to cross BBB/BTB with high efficiency, providing powerful support for their use as intracranial drug carriers. These mechanisms by which EVs are able to cross the BBB/BTB are mainly due to their surface-rich membrane proteins that promote endothelial cell uptake. For example, recent studies have shown that EVs from ginseng and grapefruit can spontaneously promote the entry of chemotherapeutic drugs into the brain. The cell membrane coated bionic nano-particle is a novel nano-carrier, and the surface of the nano-carrier is imitated to the biological membrane structure of a specific cell membrane. Due to their cell membrane-like properties, such nanoparticles have significant advantages and potential applications in the fields of drug delivery, cancer treatment, immunomodulation, etc. By inheriting the components and characteristics of cell membranes, such particles generally have good biocompatibility and can reduce immune responses and toxic and side effects to the body. Meanwhile, as the receptor and the molecule on the cell membrane can identify specific cells, the receptor and the molecule can realize high-efficiency targeted delivery through the combination with the receptor on the surface of the target cells in the blood circulation, so that the concentration of the drug at the target site is increased, and the influence on non-target tissues is reduced. In addition, the cell membrane provides a natural barrier that protects the drug-carrying molecule from premature degradation, thereby improving the stability and bioavailability of the drug. Therefore, the surface modification of the nanoparticle by using the plant-derived extracellular vesicles may provide a more effective strategy for the treatment of intracranial nervous system diseases such as glioma. Disclosure of Invention The invention aims to provide a bionic phase change nanoparticle modified by an extracellular vesicle of a grapefruit, which can automatically cross BBB/BTB, overcome biological barriers of intracranial administration, and directly act on nerve cells by carrying medicines or functional molecules, thereby providing a new treatment scheme for effectively treating intracranial nervous system diseases such as glioma and the like. Specifically, the invention adopts the following technical scheme: the bionic phase change nanoparticle modified by the grape fruit extracellular vesicles is named EV@NP, the bionic phase change nanoparticle is obtained by compounding phase change nanoparticle NP carrying a sound sensitive agent with grape fruit extracellular vesicles GFEV, and the NP is obtained by compounding disulfide bridge polyphosphate SS-PPE, perfluoro-n-pentane PFP and hematoporphyrin monomethyl ether HMME. Wherein hematoporphyrin monomethyl ether HMME is an acoustic sensitizer, perfluoro-n-pentane is a phase change material, and the acoustic sensitizer has the main function of generating active oxygen to kill cells after ultrasonic stimulation (namely acoustic power treatment). The EV@NP surface is provided with a membranous structure, and the grape fruit extracellular vesicles GFEV are coated on the phase-change nano-particle NP surface, wherein the diameter of the EV@NP is 110-150nm, preferably 110-120nm. The inv