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CN-122005846-A - Atropine-carried responsive disintegrating nanoparticle, preparation method and application thereof in myopia treatment

CN122005846ACN 122005846 ACN122005846 ACN 122005846ACN-122005846-A

Abstract

The invention belongs to the technical field of biological medicines, relates to a responsive disintegrating nanoparticle carrying atropine, a preparation method and application thereof in myopia treatment, and in particular relates to the responsive disintegrating nanoparticle carrying atropine, the preparation method of the nanoparticle and the application of the responsive disintegrating nanoparticle carrying atropine in myopia treatment through accurate space-time regulation of scleral fiber microenvironment. The invention firstly provides a nanoparticle targeting ROS responsive disintegration, which takes Zn 2+ as a center and reacts with a ligand H 2 L to form spherical nanoparticles, wherein L represents C 11 H 18 O 4 S 2 2‑ .

Inventors

  • SHI YI
  • JIANG LINGXI
  • PENG GUISEN
  • MIAO YANGBAO

Assignees

  • 四川省医学科学院·四川省人民医院

Dates

Publication Date
20260512
Application Date
20260204

Claims (10)

  1. 1. The targeted ROS responsive disintegrated nanoparticle is characterized by being self-assembled by taking Zn 2+ as a center and reacting with a ligand H 2 L to form a spherical nanoparticle, wherein L represents C 11 H 18 O 4 S 2 2- , and the ligand provides-SH and-COOH to react with Zn 2+ in a coordination manner to form the targeted ROS responsive disintegrated nanoparticle.
  2. 2. The ROS-responsive disintegrating-targeted nanoparticle of claim 1, wherein the nanoparticle has a pore structure inside.
  3. 3. The ROS-responsive disintegrating-targeted nanoparticle of claim 1, wherein the nanoparticle has a particle size in the range of 100-200nm.
  4. 4. The ROS-responsive disintegrating-targeted nanoparticle of claim 1, wherein the nanoparticle is loaded with an anti-inflammatory drug, wherein the anti-inflammatory drug comprises atropine.
  5. 5. The method of preparing ROS-responsive disintegrated targeted nanoparticles of claim 4, comprising the steps of: S01, weighing zinc ion powder and ligand powder, dissolving the ligand powder in a polar solvent, wherein the ligand powder is propane-2, 2-diylbis (sulfanediyl) dipropionic acid, the mass ratio of the zinc ion powder to the ligand powder is 5:2-5:4, and carrying out high-temperature oil bath reaction for 3-10h, wherein the temperature of the high-temperature oil bath reaction is higher than 120 ℃ to obtain a metal organic framework Zn NPs stock solution; s02, centrifuging, collecting and washing to obtain Zn NPs nano particles; s03, mixing the Zn NPs nanoparticle solution with the atropine solution in equal proportion, and performing ultrasonic treatment under ice bath conditions to synthesize Zn@atophine NPs nanoparticles.
  6. 6. The method according to claim 5, wherein the high temperature oil bath has a reaction time of 3 hours and a reaction temperature of 150 ℃.
  7. 7. Use of the ROS-responsive disintegrated nanoparticle of claim 4 for the manufacture of a medicament for the treatment of ocular inflammatory diseases.
  8. 8. Use of the ROS-responsive disintegrated nanoparticle of claim 4 for the manufacture of a medicament for the treatment of myopia.
  9. 9. The use according to claim 7 or 8, wherein the dosage form of the medicament comprises drops.
  10. 10. An ocular drop for treating myopia, comprising the ROS-responsive disintegrating-targeted nanoparticle of any one of claims 1-4.

Description

Atropine-carried responsive disintegrating nanoparticle, preparation method and application thereof in myopia treatment Technical Field The invention belongs to the technical field of biological medicines, relates to a responsive disintegrating nanoparticle carrying atropine, a preparation method and application thereof in myopia treatment, and in particular relates to the responsive disintegrating nanoparticle carrying atropine, the preparation method of the nanoparticle and the application of the responsive disintegrating nanoparticle carrying atropine in myopia treatment through accurate space-time regulation of scleral fiber microenvironment. Background Myopia has become one of the most common vision disorders worldwide affecting nearly one third of the population, and is mainly characterized by excessive elongation of the eyeball and remodelling of the sclera, ultimately leading to irreversible structural and functional impairment of high myopia and pathologic myopia. Current mainstream clinical strategies (including optical correction, low-dose atropine treatment, and lifestyle intervention) can only alleviate symptoms or delay progression because they do not address the underlying cellular mechanisms behind scleral remodeling. Recent studies have revealed that scleral fibroblasts play a key role in posterior extra-articular matrix (ECM) renewal and mechanical homeostasis. A deregulation of fibroblast activity can disrupt collagen cross-linking and induce abnormal biomechanical signals, driving eye elongation. Notably, emerging studies indicate that there is dynamic assembly of membraneless biomolecular microenvironments within fibroblasts, which in turn regulate transcriptional networks associated with ECM synthesis. However, the spatial and temporal regulatory mechanisms in ocular fibroblasts are still unclear, and precise regulation of this process has not been achieved due to the complex intracellular environment and lack of efficient delivery tools. The anticholinergic drug atropine is the most widely accepted means of pharmaceutical intervention to control myopia progression. Although the low-dose atropine eyedrops have clinical effects, the effects are limited by the problems of poor ocular permeability, rapid removal through the nasolacrimal duct, limited bioavailability of the posterior segment, and the like. In addition, it is difficult for the conventional pharmaceutical formulation to reach the fibroblast compartment at physiological concentration, and thus the conventional atropine formulation cannot exert therapeutic effects by modulating biophysical processes such as intracellular signaling or oxidative stress. In view of the above, there is a need for new pharmaceutical formulations that alleviate the deficiencies of the prior art. Disclosure of Invention The invention aims to provide a responsive disintegrating nanoparticle and a scheme for releasing a drug to treat myopia by targeting ROS disintegration, and the invention adopts the following technical scheme. In a first aspect, the present invention provides a nanoparticle and a method for preparing the same. A targeted ROS-responsive disintegrated nanoparticle, said nanoparticle being self-assembled to form a spherical nanoparticle by reaction with a ligand H 2 L centered on Zn 2+, wherein L represents C 11H18O4S22-, said ligand providing a coordination reaction of-SH and-COOH with Zn 2+ to form said targeted ROS-responsive disintegrated nanoparticle. The ligand structure is as follows: HOOC-(CH2)3-S-C(CH3)2-S-(CH2)3-COOH; molecular formula C 11H20O4S2; The reaction equation is as follows: Ligand H 2L（L = C11H18O4S2²-, a fully deprotonated form, each L2 - can provide 4 coordinating atoms (2O from carboxylate, 2S from thioether) coordinated to Zn2 +. The net equation (regardless of the exact MOF stoichiometry) can be written as: ; wherein [ ZnL ] n represents the metal-organic framework polymer formed. Further, the nanoparticle has a pore structure inside. Further, the particle size of the nanoparticle ranges from 100 to 200nm. Further, the nanoparticle carries a drug with anti-inflammatory effect, including, but not limited to, atropine. The preparation method of the nanoparticle targeting ROS responsive disintegration comprises the following steps: S01, weighing zinc ion powder and ligand powder, dissolving the ligand powder in a polar solvent, wherein the ligand powder is propane-2, 2-diylbis (sulfanediyl) dipropionic acid, the mass ratio of the zinc ion powder to the ligand powder is 5:2-5:4, and carrying out high-temperature oil bath reaction for 3-10 hours, wherein the temperature of the high-temperature oil bath reaction is higher than 120 ℃ to obtain a metal organic framework Zn NPs stock solution; s02, centrifuging, collecting and washing to obtain Zn NPs nano particles; s03, mixing the Zn NPs nanoparticle solution with the atropine solution in equal proportion, and performing ultrasonic treatment under ice bath conditions