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CN-121971406-A - Nanometer drug-carrying system for targeted removal of liver aging cells and regulation and control of oxidative stress, and preparation method and application thereof

CN121971406ACN 121971406 ACN121971406 ACN 121971406ACN-121971406-A

Abstract

The invention relates to a nanometer medicine carrying system for removing liver aging cells in a targeting way and regulating and controlling oxidative stress, and a preparation method and application thereof, wherein the nanometer medicine carrying system comprises the following components: cerium doped zinc-based metal organic framework nano particles, a drug loaded in a hollow mesoporous structure of the nano particles, and mesenchymal stem cell membranes modified on the surfaces of the nano particles. The invention constructs a nano medicine carrying system for breaking the aging-inflammation circulation based on the interaction relation between aging cells and non-alcoholic fatty liver, which can improve the enrichment efficiency and the residence time of the non-alcoholic fatty liver disease part, and improves the targeting of liver aging cells, the synergistic effect and the safety of removing the aging cells and regulating the inflammation environment and improves the liver lipid metabolism and the inflammation environment by utilizing hollow mesoporous metal organic framework nano particles with high-efficiency active oxygen removal and high medicine carrying rate to carry medicines and two links of medicine delivery and release.

Inventors

  • PEI RENJUN
  • WANG CHENGLONG
  • WANG LI

Assignees

  • 中国科学院苏州纳米技术与纳米仿生研究所

Dates

Publication Date
20260505
Application Date
20260211

Claims (10)

  1. 1. A nano medicine carrying system for eliminating liver aging cells in a targeting way and regulating and controlling oxidative stress is characterized by comprising cerium doped zinc-based metal organic framework nano particles, medicines loaded in a hollow mesoporous structure of the nano particles and mesenchymal stem cell membranes modified on the surfaces of the nano particles.
  2. 2. The nano-drug delivery system of claim 1, wherein the cerium doped zinc based metal organic framework nano-particles have a hollow spherical structure with a particle size of 60-80 nm.
  3. 3. The nano-drug delivery system according to claim 1 or 2, wherein the drug is a drug having liver senescent cell removal efficacy; Preferably, the drug comprises PROTAC drugs ARV825, ABT263, dasatinib, or quercetin.
  4. 4. The nanodrug delivery system according to any one of claims 1-3, wherein the thickness of the mesenchymal stem cell membrane is 10-15 nm.
  5. 5. The nanodrug delivery system of any of claims 1-4, wherein the mass ratio of cerium doped zinc based metal organic framework nanoparticles to drug is 1 (1-3).
  6. 6. The nano-drug delivery system according to any one of claims 1 to 5, wherein the cerium doped zinc-based metal organic framework nano-particles are prepared by mixing cerium ion salt and zinc ion salt as metal sources, organic ligands and surfactants and reacting the cerium ion salt and the zinc ion salt with each other; Preferably, the molar ratio of the cerium ion salt to the zinc ion salt is 1 (1-2); preferably, the organic ligand comprises imidazole-2-carbaldehyde; Preferably, the method comprises the steps of, the surfactant comprises polyvinylpyrrolidone; Preferably, the cerium ion salt comprises cerium acetylacetonate and the zinc ion salt comprises zinc acetate dihydrate.
  7. 7. The method of preparing a nanodrug delivery system according to any one of claims 1-6, comprising the steps of: (1) Dispersing cerium doped zinc-based metal organic framework nano particles in a drug solution, mixing, incubating, and carrying out solid-liquid separation to obtain drug-loaded nano particles; (2) Mixing the drug-loaded nano particles with bone marrow mesenchymal stem cell membranes, and performing ultrasonic incubation to perform membrane coating to obtain the nano drug-loading system.
  8. 8. Use of a nanodrug delivery system according to any of claims 1-6 for the preparation of a product for targeting and eliminating liver senescent cells.
  9. 9. Use of a nanodrug delivery system according to any of claims 1-6 for the preparation of a product targeting senescent cells of the liver and scavenging active oxygen.
  10. 10. Use of the nanodrug delivery system according to any one of claims 1-6 for the preparation of a product for preventing, alleviating or treating non-alcoholic fatty liver disease.

Description

Nanometer drug-carrying system for targeted removal of liver aging cells and regulation and control of oxidative stress, and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and relates to a nano medicine carrying system for targeted removal of liver aging cells and regulation and control of oxidative stress, and a preparation method and application thereof. Background Non-alcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome, with lifestyle changes, NAFLD has become one of the most common liver diseases, and the overall disease burden of NAFLD-related liver disease at different stages has increased. NAFLD has complex pathogenesis including race, genetic susceptibility, eating habits, metabolism, immunity, intestinal flora, insulin resistance, lipid metabolism disorders and interactions between their triggered inflammatory responses, etc. The existing common NAFLD treatment means comprise life style intervention, weight-reducing operation, regulation of intestinal microbiota, drug treatment including insulin sensitizer, antioxidant, cholesterol-lowering drug and the like, and only through metabolic regulation, the NAFLD treatment means is a mode for treating both symptoms and root causes. Clinical trial results have found that the presence of hepatocyte senescence, an irreversible cell cycle arrest state, in the liver of NAFLD patients can be induced by a variety of stressors, including telomere dysfunction, as well as genotoxicity and oxidative stress. Senescent cells often increase the secretion of large amounts of pro-inflammatory factors, collectively known as the senescence-associated secretory phenotype (SASP), which can induce tissue dysfunction in paracrine fashion. Aging cells impair hepatic mitochondrial beta oxidation, impaired fat metabolism, promote triglyceride accumulation, mitochondrial dysfunction, cell autonomous steatosis, reduced oxidative phosphorylation, and increased Reactive Oxygen Species (ROS) production. Reactive Oxygen Species (ROS) increase, disrupting cellular redox balance, leading to DNA damaging reactions, accelerating telomere erosion, and thus leading to cellular senescence, which can form a vicious circle. In conclusion, if the 'aging-inflammation' circulation is broken, the liver fat metabolism is improved, and the method is one of the problems to be solved for treating the non-alcoholic fatty liver. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a nano drug-carrying system for removing liver aging cells in a targeted way and regulating and controlling oxidative stress, and a preparation method and application thereof. According to the nano drug-carrying system, the nano particles are subjected to bionic modification through the mesenchymal stem cell membrane, so that the distribution rule of the nano particles in a human body is changed, the nano particles can be more efficiently enriched in a liver inflammation area, and the aged liver cells are precisely targeted, so that the removal of the aged cells and the removal of active oxygen are further realized. The product can effectively regulate local inflammation microenvironment of liver, improve lipid metabolism imbalance and inhibit further generation of new aging cells, thereby constructing a high-efficiency nanometer treatment system with dual functions of targeted aging cell removal and antioxidation. In order to achieve the aim of the invention, the invention adopts the following technical scheme: In a first aspect, the invention provides a nano drug delivery system for targeted removal of liver aging cells and regulation of oxidative stress, which comprises cerium doped zinc-based metal organic framework nano particles, drugs loaded in hollow mesoporous structures of the nano particles, and mesenchymal stem cell membranes modified on the surfaces of the nano particles. The invention develops a nano drug-carrying system capable of removing aging cells in a targeting way and regulating and controlling oxidative stress, and changes the distribution rule of nano particles in a body by carrying out surface modification on mesenchymal stem cell membranes, so that the nano particles are more efficiently enriched at liver inflammation parts. After reaching the liver inflammation part, the nano particles target to the aging cells, and the aging cells are selectively cleared through the medicine loaded in the nano particles, on the basis, the active oxygen in the whole liver inflammation environment is cleared by utilizing the characteristics of cerium doped zinc-based metal organic framework pseudoenzyme, the generation of the new aging cells is inhibited, and the multi-stage functional cascade of 'targeting the liver inflammation part', 'clearing the aging cells' and 'regulating the inflammation environment to inhibit the generation of the new aging cells' is realized