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The construction and application of catalytic nanoparticles based on glucose oxidase/iron phosphate

A glucose oxidase and nanoparticle technology, applied in the field of nanodiagnostic agent preparation, can solve the problems of insufficient Fenton reaction to maintain high efficiency, Fenton reaction obstruction, etc., and achieve enhanced chemodynamic therapy, significant inhibitory effect, and mild preparation process. Effect

Active Publication Date: 2022-05-27
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the slightly acidic solid tumor microenvironment (pH 6.5-6.9) blocks the Fenton response
Again, although H 2 o 2 Overexpressed (0.1-1.0 mM) in solid tumors, but levels are still insufficient to maintain an efficient Fenton response

Method used

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  • The construction and application of catalytic nanoparticles based on glucose oxidase/iron phosphate
  • The construction and application of catalytic nanoparticles based on glucose oxidase/iron phosphate
  • The construction and application of catalytic nanoparticles based on glucose oxidase/iron phosphate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Take 2.6 mL of ammonia water, 90 mL of ethanol, and 40 mL of distilled water, respectively, and magnetically stir them in a water bath at 45 °C to fully mix them. After 15 minutes, 10 mL of a 50 mg / mL dopamine monomer aqueous solution was added. After 12 h of reaction, centrifuge purification (16000 rpm, 10 min) to collect polydopamine nanoparticles (PDA).

[0045] According to the mass ratio of 1:1, the prepared polydopamine nanoparticles and glucose oxidase were mixed in 10 mM Tris buffer with pH 8.5, stirred in a water bath at 37 °C for 24 hours, and purified by centrifugation to obtain the loaded glucose oxidized. Enzymatic polydopamine nanoparticles (PDA-GOx).

[0046] The aqueous solutions of PDA-GOx and bovine serum albumin BSA were mixed in a mass ratio of 1:2, and the reaction solution was a phosphate buffer at pH 7.4. After 24 hours of magnetic stirring at room temperature, the BSA-encapsulated PDA-GOx nanoparticles (PDA-GOx-BSA) were obtained by centrifugat...

Embodiment 2

[0050] The PDA-GOx-BSA-FePi nanoparticles prepared in Example 1 were taken and prepared into aqueous solutions of 50, 100, 200, 300, and 400 ppm, and placed in a quartz dish for laser irradiation. The laser wavelength used is 808 nm and the power per unit area is 1.0W / cm 2 . Temperatures were recorded every 0.5 min during the laser process for a total of 10 min.

[0051] Heat production test results ( figure 2 ) showed that the temperature of the solution gradually increased with the laser irradiation. The magnitude of the temperature rise is positively correlated with the nanoparticle concentration. This indicates that the obtained composite nanoparticles have good photothermal effect.

Embodiment 3

[0053] The PDA-GOx-BSA-FePi nanoparticles prepared in Example 1 were mixed with glucose, and the pH value was monitored in real time by a pH meter. 1.44 mg of PDA-GOx-BSA-FePi nanoparticles were mixed with 10 mL of glucose at different concentrations (200, 400, 600, 800 ppm) and stirred in a 37 °C water bath, which was continuously fed with oxygen. Changes in pH were recorded at different time points (1, 3, 6, 9 h).

[0054] Take the PDA-GOx-BSA nanoparticles prepared in Example 1, and use ammonium titanium oxalate as an indicator to measure H 2 O 2 concentration. 1.00 mg of PDA-GOx-BSA was mixed with 2 mL of glucose at various concentrations (25, 50, 100, 200, 300 ppm). At certain time points (1, 3, 6, 9 h), the mixture was centrifuged to collect the supernatant. Then 0.8 mL of the supernatant was mixed with 0.2 mL of 0.01 M ammonium oxalate solution, and the absorbance at 405 nm was analyzed with a UV-Vis spectrophotometer to calculate H 2 O 2 concentration.

[0055] ...

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Abstract

The invention relates to the construction and application of a catalytic nanoparticle based on glucose oxidase / iron phosphate, comprising: preparing polydopamine nanoparticles; loading glucose oxidase, bovine serum albumin and iron phosphate on the polydopamine nanoparticles in sequence . Among them, glucose oxidase can consume glucose at the tumor site to generate gluconic acid and hydrogen peroxide to achieve starvation therapy; iron phosphate can generate ferrous iron under the reducing effect of polydopamine; hydrogen peroxide can be decomposed by divalent iron under acidic conditions Iron catalyzes the generation of highly toxic hydroxyl radicals to achieve self-enhanced chemodynamic therapy; polydopamine can respond to near-infrared light to achieve low-temperature photothermal therapy with the assistance of starvation therapy. Under the guidance of photoacoustic imaging, the obtained composite nanoparticles can achieve significant inhibition of tumor growth through the combination therapy of three modalities, and provide new ideas for the diagnosis and treatment of malignant tumors.

Description

technical field [0001] The invention belongs to the field of preparation of nano-diagnostic agents for tumors, in particular to the construction of a catalytic nano-particle based on glucose oxidase / iron phosphate, and its application in tumor photoacoustic imaging / starvation therapy / chemodynamic therapy / low temperature photothermal therapy diagnostic applications. Background technique [0002] Chemodynamic therapy (CDT), proposed in 2016, is considered to be a promising tumor therapy. Using the chemical energy in metal ion-mediated Fenton or Fenton-like reactions, hydrogen peroxide (H 2 O 2 ) produces highly toxic hydroxyl radicals ( OH). This strategy has pH and H 2 O 2 It shows high tumor specificity depending on the intrinsic characteristics. These characteristics enable CDT to have better biocompatibility and lower toxicity to normal tissues. In addition, compared to other reactive oxygen species (ROS)-based strategies such as photodynamic therapy (requiring exte...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K41/00A61K38/44A61K9/51A61K47/42A61K47/34A61P35/00B82Y5/00B82Y40/00B82Y20/00
CPCA61K49/221A61K49/225A61K41/0052A61K38/443C12Y101/03004A61K9/5169A61K9/5192A61K9/513A61P35/00B82Y5/00B82Y40/00B82Y20/00
Inventor 刘辉王静静陆世玉胡洁唐薇阳文婷
Owner SOUTHWEST UNIV
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