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Gas synergistic sonodynamic modified albumin drug nanoparticles, and preparation method and application thereof

A nanoparticle and albumin technology, applied in the field of new biomedical materials, can solve the problems of inability to achieve the effect of gas synergistic sonodynamic therapy, uncontrollable release of drugs, and no consideration of albumin modification, etc., to facilitate large-scale preparation , good dispersibility, sufficient effect of releasing NO signal molecules

Inactive Publication Date: 2021-11-02
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In short, the existing technology has the problem that albumin nanoparticles cannot controlly release drugs under physiological conditions, and can only release drugs slowly under endogenous stimuli such as acidity or reduction, while light-controlled release has poor tissue penetration, resulting in Defects such as low drug release need to be solved urgently
[0005] Chinese invention patent (application) CN202010186222.2 discloses an albumin nanoparticle that can be activated by ultrasound to release drugs, its preparation method and application. It uses an azo cross-linking agent and carries a chemotherapeutic drug for ultrasound release, but the patent uses Albumin is unmodified albumin, without considering the modification of albumin, it does not involve the release of NO signal molecules, does not involve the entrapment of sound sensitizer drugs, and cannot achieve the therapeutic effect of gas synergy with sonodynamics

Method used

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  • Gas synergistic sonodynamic modified albumin drug nanoparticles, and preparation method and application thereof
  • Gas synergistic sonodynamic modified albumin drug nanoparticles, and preparation method and application thereof
  • Gas synergistic sonodynamic modified albumin drug nanoparticles, and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0051] Preparation of Modified Albumin Containing SNO Structure Capable of Ultrasonic Release of NO Gas

[0052] Weigh 90 mg of bovine serum albumin and dissolve it in 3 ml of ultrapure water, stir for 1 h, add 37 ul of tert-butyl nitrite, and react at room temperature for 12 h under stirring conditions (stirring at 400-600 rpm), then use The dialysis bag was dialyzed to obtain a modified albumin (BSA-SNO) solution containing a SNO structure capable of ultrasonically releasing NO gas.

Embodiment 2

[0054] Preparation of Molecular Active Ester of Chemical Crosslinker

[0055] Weigh 50 mg of 4,4'-azobis(4-cyanovaleric acid) into a 25 mL flask, add 2 mL of anhydrous dimethyl sulfoxide to it, and magnetically stir until completely dissolved. Under stirring conditions, 50 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 80 mg of N-hydroxysuccinimide were successively added until all were dissolved. After reacting for two hours at 37°C, a colorless and clear 4,4'-azobis(4-cyanovaleric acid) active ester solution was obtained.

Embodiment 3

[0057] Preparation of Albumin Drug Nanoparticles Modified by Gas and Acoustic Dynamics

[0058] Modified bovine serum albumin-based nanoparticles (BSASNO-ACVA-sonosensitizer) were prepared by a desolvation-chemical crosslinking method. In principle, measure 3ml of the BSA-SNO solution prepared in Example 1, measure 4mg of the sound sensitizer TCA and add it to the BSA-SNO solution, stir at room temperature, fully dissolve for 2 hours, and dissolve with 0.1M NaOH to adjust the pH value to 8. Add 8 mL of absolute ethanol dropwise at a constant speed of 4 mL / min. After the desolvation process is completed, slowly add the crosslinking agent solution prepared in Example 2 (4,4'-azobis(4-cyanovaleric acid ) active ester solution) 80 μL for cross-linking and solidification, and react overnight at 37°C in the dark to obtain a stable modified albumin BSASNO-ACVA-sound sensitizer nanoparticle solution, high-speed centrifugation, and freeze-drying to obtain gas synergistic sonodynamic mo...

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Abstract

The invention discloses a gas synergistic sonodynamic modified albumin drug nanoparticle and a preparation method and application thereof. The nanoparticle comprises a modified albumin molecule, a sound-sensitive agent and a chemical crosslinking molecule, and modified albumin molecules are used as a nanoparticle skeleton, small molecules containing azo groups are used as a chemical cross-linking agent, and a sound-sensitive agent is coated. The modified albumin has a donor structure capable of effectively performing ultrasonic excitation to release NO, NO reacts with superoxide anions to form peroxynitrite, protein functions can be changed, DNA can be damaged, and the modified albumin is helpful to cooperate with a sound-sensitive agent to kill tumor cells and intracellular pathogens; and through the chemical cross-linking agent with the azo group, the azo bond can be broken under the ultrasonic action to generate free radicals, so that the nanoparticles are damaged to release the entrapped medicine, and the release amount of the medicine is related to the ultrasonic time and intensity, so that the purpose of controllable medicine release is achieved.

Description

technical field [0001] The invention belongs to the field of biomedical new materials, and in particular relates to a gas synergistic sonodynamically modified albumin drug nanoparticle, a preparation method thereof, and an application of the drug release through ultrasonic action. Background technique [0002] Albumin is the most abundant serum protein in the blood. It is often selected as a drug carrier due to its high water solubility, good stability, and high biocompatibility. There are a large number of amino acid residues in the primary structure of albumin, which is Several small molecules (ligands) provide binding sites and are capable of payloads for many different classes of drugs. As the carrier of drug delivery, human serum albumin (HSA) and bovine serum albumin (BSA) are the most studied. HAS is a soluble single-chain globular protein with a molecular weight of 67kDa and composed of 585 amino acids. HAS has many drug binding sites and can bind to salicylic acid,...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/655A61K47/64A61K47/69A61P35/00
CPCA61K41/0033A61K31/655A61K47/643A61K47/6931A61P35/00A61K2300/00
Inventor 杜健军张苇杭时天聪樊江莉彭孝军
Owner DALIAN UNIV OF TECH
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