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CN-122010125-A - Bowl-shaped Janus mesoporous silica nano motor and preparation method and application thereof

CN122010125ACN 122010125 ACN122010125 ACN 122010125ACN-122010125-A

Abstract

The invention provides a bowl-shaped Janus mesoporous silica nano motor and a preparation method and application thereof, belonging to the technical field of novel biomedical materials and eye disease treatment. According to the invention, ZIF-8 nanocubes are used as seeds, tetraethoxysilane is used as a silicon source to prepare ZIF-8& mSiO 2 anisotropic nanometer hybrids, then amino functional modification is carried out, ZIF-8 inner cores are removed by etching, amino functional bowl-shaped mesoporous silica is obtained, and catalase is asymmetrically and covalently grafted on the outer surface of the bowl-shaped Janus mesoporous silica nanometer motor through amino active sites on the surface of B-mSiO 2 &NH 2 . The nano motor prepared by the invention can realize directional autonomous movement in the presence of an infection part H 2 O 2 , effectively enhance the penetration capability of the drug across the cornea barrier, penetrate deep into the cornea stroma and the bacterial biofilm, and solve the problem of low delivery efficiency of the traditional drug.

Inventors

  • ZHANG HENGRUI
  • XIE LIXIN
  • LI XIAOMIN
  • LIU MINCHAO
  • REN HUIFANG
  • ZHAN YATING

Assignees

  • 山东第一医科大学附属眼科研究所(山东省眼科研究所、山东第一医科大学附属青岛眼科医院)

Dates

Publication Date
20260512
Application Date
20260210

Claims (10)

  1. 1. The preparation method of the bowl-shaped Janus mesoporous silica nano motor is characterized by comprising the following steps of: (1) Taking a ZIF-8 nano cube with a truncated rhombic dodecahedron structure as a seed, taking tetraethoxysilane as a silicon source and triethylamine as a catalyst in a biphase reaction system containing a water phase and an organic phase, and enabling mesoporous silicon dioxide to grow on a {100} crystal face of the ZIF-8 nano cube to form a ZIF-8& mSiO 2 anisotropic nano hybrid; (2) Performing amino functional modification on the ZIF-8& mSiO 2 anisotropic nano hybrid to obtain ZIF-8& mSiO 2 &NH 2 ; (3) Etching to remove ZIF-8 kernel in the ZIF-8& mSiO 2 &NH 2 to obtain amino functionalized bowl-shaped mesoporous silica; (4) And (3) asymmetrically and covalently grafting catalase on the outer surface of the bowl-shaped mesoporous silica surface through the amino active site on the amino functionalized bowl-shaped mesoporous silica surface to form the B-mSiO 2 & CAT nano motor with a Janus structure, namely the bowl-shaped Janus mesoporous silica nano motor.
  2. 2. The method for preparing a bowl-shaped Janus mesoporous silica nanomotor according to claim 1, wherein in the step (1), the organic phase is cyclohexane, the reaction temperature is 60 ℃, and the reaction time is 12 hours; the dosage ratio of the ZIF-8 nanocube to the tetraethoxysilane is 15mg to 100 mu L.
  3. 3. The method for preparing a bowl-shaped Janus mesoporous silica nanomotor according to claim 1, wherein in the step (2), the step of performing amino-functional modification on the anisotropic nanohybrid specifically comprises: Dispersing the ZIF-8& mSiO 2 anisotropic nano hybrid in ethanol to obtain a dispersion liquid of 2mg/mL, then adding (3-aminopropyl) triethoxysilane, heating to 80 ℃ and reacting for 24 hours at constant temperature to obtain the ZIF-8& mSiO 2 &NH 2 ; The dosage ratio of the (3-aminopropyl) triethoxysilane to the ZIF-8& mSiO 2 anisotropic nanometer hybrid is 1mL to 200mg.
  4. 4. The method for preparing the bowl-shaped Janus mesoporous silica nano motor according to claim 1, wherein in the step (3), the step of etching and removing the ZIF-8 core in the ZIF-8& mSiO 2 &NH 2 specifically comprises the following steps: And dispersing the ZIF-8& mSiO 2 &NH 2 in a dilute hydrochloric acid solution, and stirring and reacting for 2 hours to obtain the amino-functionalized bowl-shaped mesoporous silica B-mSiO 2 &NH 2 .
  5. 5. The method for preparing the bowl-shaped Janus mesoporous silica nanomotor according to claim 1, wherein in the step (4), asymmetric grafting of catalase is realized by adopting EDC/NHS chemical coupling method, and the method specifically comprises the following steps: dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in a phosphate buffer solution, adding catalase to react at room temperature to obtain an activated catalase solution, and then adding the activated catalase solution into the dispersion of the amino-functionalized bowl-shaped mesoporous silica B-mSiO 2 &NH 2 , and stirring overnight at room temperature in a dark place to realize asymmetric grafting of the catalase.
  6. 6. The method for preparing the bowl-shaped Janus mesoporous silica nanomotor according to claim 5, wherein the mass ratio of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, the N-hydroxysuccinimide and the catalase is 30:40:1.
  7. 7. The method for preparing a bowl-shaped Janus mesoporous silica nanomotor according to claim 5, wherein the volume ratio of the activated catalase solution to the dispersion of the amino-functionalized bowl-shaped mesoporous silica B-mSiO 2 &NH 2 is (3-5) to 1.
  8. 8. A bowl-shaped Janus mesoporous silica nanomotor prepared according to the preparation method of any one of claims 1 to 7.
  9. 9. Use of a bowl-shaped Janus mesoporous silica nanomotor according to claim 8 for the manufacture of a medicament for the treatment of bacterial keratitis.
  10. 10. The use of a bowl-shaped Janus mesoporous silica nanomotor according to claim 9 for preparing a medicament for treating bacterial keratitis, comprising the steps of dispersing the bowl-shaped Janus mesoporous silica nanomotor in a riboflavin aqueous solution, loading riboflavin by mesoporous adsorption, and obtaining a bowl-shaped Janus mesoporous silica nanomotor active drug delivery system.

Description

Bowl-shaped Janus mesoporous silica nano motor and preparation method and application thereof Technical Field The invention belongs to the technical field of novel biomedical materials and eye disease treatment, and particularly relates to a bowl-shaped Janus mesoporous silica nano motor and a preparation method and application thereof. Background Bacterial keratitis is a corneal inflammatory disease caused by bacterial infection, and is one of the main causes of corneal blindness. The cornea, which is the outermost transparent tissue of the eyeball, plays an important role in light transmission and refraction, but its structural integrity is extremely susceptible to microbial attack. The bacteria can release protease and exotoxin after invading, destroy cornea collagen matrix, cause serious consequences such as matrix necrosis, perforation and the like, activate organism immune response, recruit immune cells to release inflammatory mediators, and further aggravate cornea injury. At present, the clinical treatment of bacterial keratitis mainly depends on the combination of antibiotics and anti-inflammatory drugs, but with the increasing number of multi-drug resistant (MDR) strains, the treatment effect of the traditional antibiotics is greatly reduced. In addition, the corneal biological barrier results in the difficulty of penetration of the drug into the deep stroma of the cornea, the biofilm formed at the site of infection can hinder the drug from contacting bacteria, and the hypoxic microenvironment induced by the infection further reduces the therapeutic efficiency, which factors together constitute a significant challenge in the treatment of bacterial keratitis. The cornea collagen Crosslinking (CXL) technology uses Riboflavin (RF) as a photosensitizer, and the covalent crosslinking of cornea stroma collagen is induced by ultraviolet A (UVA) irradiation, and meanwhile, reactive Oxygen Species (ROS) are generated to play an antibacterial role, so that a new direction is provided for the non-antibiotic treatment of multi-drug resistant bacterial infectious keratitis. However, the technology has obvious limitations that firstly, the bioavailability of the riboflavin is low, the riboflavin is difficult to penetrate through a biological membrane and cornea stroma to reach the deep part of infection, and secondly, the generation of ROS is highly dependent on oxygen, and the anaerobic environment of the infection part seriously weakens the antibacterial effect and the collagen crosslinking efficiency. The nano-carrier technology provides a new idea for improving the delivery of ocular medicaments, such as metal organic frameworks, mesoporous silica nano-particles and the like, which have been used for medicament loading and delivery, but the carriers depend on passive diffusion and have limited penetration capacity across cornea barriers. The nanomotor is used as an intelligent nanomaterial capable of converting chemical energy and the like into autonomous motion capability, and provides possibility for realizing active targeting drug delivery. In bacterial keratitis, the elevated levels of hydrogen peroxide (H 2O2) within the infectious microenvironment gives the unique advantage of Catalase (CAT) driven nanomotors that can use site-specific hydrogen peroxide to achieve autonomous propulsion while generating oxygen (O 2) to relieve hypoxia, thus becoming a highly efficient vehicle for riboflavin delivery in corneal collagen cross-linking therapy. The anisotropic distribution of enzymes is critical to optimize the performance of the catalase driven nanomotor. However, conventional nanocarriers generally have uniform surface chemistry and it is difficult to achieve spatially selective functionalization. Although interface-based masking strategies can achieve anisotropy, they involve complex multi-step synthesis processes, are inefficient and difficult to adapt to a wide variety of nanostructures. Therefore, development of a general and simplified preparation method, realizing in-situ site-specific masking in the nanoparticle synthesis process, has important significance for advancing biomedical applications based on nanomotors. Disclosure of Invention The invention provides a bowl-shaped Janus mesoporous silica nano motor and a preparation method and application thereof, and aims to solve the problems that the traditional medicine for treatment has poor penetration, the anaerobic environment influences the curative effect, and the drug-resistant bacteria are difficult to remove. In order to achieve the above purpose, the present invention provides the following technical solutions: the invention provides a preparation method of a bowl-shaped Janus mesoporous silica nano motor, which comprises the following steps: (1) Taking a ZIF-8 nano cube with a truncated rhombic dodecahedron structure as a seed, taking tetraethoxysilane as a silicon source and triethylamine as a catalyst in a biphase reaction system conta