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Nano catalyst for tumor treatment, and preparation method and application thereof

A nano-catalyst and tumor treatment technology, applied in the field of nano-catalyst for tumor treatment and its preparation, can solve the problems of tumor metastasis, limiting treatment efficiency, etc., and achieve the effects of prolonging circulation time, high catalytic efficiency, and warm working conditions

Active Publication Date: 2020-04-10
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It is well known that in the common treatments of cancer, such as chemotherapy, photodynamic therapy and photothermal therapy, there are various problems that limit their therapeutic efficiency or easily induce undesired tumor metastasis.

Method used

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  • Nano catalyst for tumor treatment, and preparation method and application thereof
  • Nano catalyst for tumor treatment, and preparation method and application thereof
  • Nano catalyst for tumor treatment, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] The preparation of embodiment 1 nanometer catalyst

[0050] 1. Preparation of composite nanozyme encapsulating iron core in glucose oxidase:

[0051] At 25°C, 5 mg of glucose oxidase and 1 mL of 25 mmol / L ferrous ammonium sulfate were dissolved in deoxygenated deionized water, and the solution was magnetically stirred for 30 min under nitrogen protection. Then, 2.5 mL of 7.5 mmol / L sodium borohydride (NaBH 4 ). After reacting for 2 hours, purify the product with an ultrafiltration tube. The molecular weight cut-off of the ultrafiltration membrane is 10000KDa, the centrifugation speed is 4000rpm, and the centrifugation time is 10min. Nanozyme, named GOx-Fe.

[0052] 2. Preparation of red blood cell membrane:

[0053] Take 5mL of mouse whole blood, centrifuge at 4°C, 2500rpm for 5min, remove the upper liquid; add 5mL of normal saline to the lower layer, pipette repeatedly, centrifuge at 4°C, 2500rpm for 5min, remove the supernatant, repeatedly wash the lower layer wit...

Embodiment 2

[0061] Embodiment 2 drug release experiment in vitro

[0062] The prepared GOx-Fe@RI-A was dissolved in 1 mol / L PBS with pH=7.4 and pH=5.4, respectively. The nanoparticle solution of each group was sealed in a dialysis bag with a molecular weight cut-off of 3500 Da and dialyzed in 10 ml of PBS. At certain intervals, 100 μl aliquots were taken from the solution outside the dialysis bag for ICP-MS detection, the content of Fe was calculated, and the drug release curve of Fe was obtained. The results were as follows: figure 2 shown. It was observed that under light irradiation, the release rate of ferrous ions at pH 7.4 was very slow, and after 48 hours, only 12.5% ​​was released. However, under light irradiation at pH 6.5 and pH 5.4, the release of ferrous ions increased to 77.3% and 82.7%, showing a clear pH-dependent ionization. It is noteworthy that under the condition of no light at pH 5.4, it exhibited reluctant release of ferrous ions. These results indicate that ligh...

Embodiment 3

[0063] Generation and measurement of embodiment 3 hydroxyl radicals

[0064] Benzoic acid (BA) was dissolved in 1 mol / L PBS at different pH (7.4, 6.5 and 5.4). GOx-Fe@RI-A (0.3 mL, 100 μg / mL) was added to a mixture solution (3 mL) containing glucose (2 mmol / L) and BA (2 mmol / L) at different pHs. At 808nm (1W / cm 2 ) after light irradiation, the change in the fluorescence spectrum of BA was monitored for 60 minutes, and the emission intensity of OHBA at 410 nm was plotted against time. The result is as image 3 shown. Such as image 3 As shown in A, after GOx-Fe@RI-A was mixed with glucose, the fluorescence spectrum of the mixture solution showed negligible changes under the conditions of pH 7.4 and light. It is worth noting that, under the same light irradiation, in the presence of glucose, GOx-Fe@RI-A at pH 6.5 and pH 5.4 ( image 3 B and 3C), with significantly enhanced fluorescence of hydroxybenzoic acid in solution, indicating that GOx-Fe@RI-A can undergo a catalytic ...

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Abstract

The invention provides a nano catalyst for tumor treatment, and a preparation method and application thereof. The nano catalyst provided by the invention comprises an erythrocyte membrane, and a composite nano enzyme and a photosensitizer which are coated in the erythrocyte membrane, wherein the composite nano enzyme comprises glucose oxidase and iron nanoparticles which are coated in an inner cavity of the glucose oxidase. The nano catalyst is preferentially accumulated at a target tumor site through targeted biomimetic delivery, and release of the composite nano enzyme is realized under irradiation of near infrared light. Based on high glucose uptake and a weakly acidic environment at the tumor site, glucose oxidase converts glucose into H2O2, induces iron nano particles to start an in-situ Fenton reaction, generates hydroxyl free radicals after sequential catalysis, induces tumor cells to be subjected to oxidative damage, and further kills the tumor cells. The nano catalyst not onlycan realize high-efficiency loading of the catalyst, but also can effectively prolong in-vivo circulation time, so that accurate and sustained release on a tumor focus part is realized, and a new thought and platform are provided for tumor treatment.

Description

technical field [0001] The invention relates to the technical field of nano-medicine, in particular to a nano-catalyst for tumor treatment and its preparation method and application. Background technique [0002] At present, cancer has become the second leading cause of death in the world. It is well known that in the common treatments of cancer, such as chemotherapy, photodynamic therapy and photothermal therapy, there are various problems that limit their therapeutic efficiency or easily induce undesired tumor metastasis. Therefore, many researchers have explored different therapeutic strategies to improve the efficiency of tumor treatment methods and achieve more focused and effective tumor-specific treatments. [0003] The microenvironment of the tumor lesion area has its particularity, such as weak acidity, high glutathione (GSH) level, hypoxia, etc., which play an extremely important role in the occurrence, development and metastasis of tumors. Nano-agents that can r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K9/50A61K47/46A61K33/26A61K38/44A61K41/00A61K47/54A61K47/62A61P35/00
CPCA61K41/0042A61K41/0057A61K33/26A61K47/6901A61K47/62A61K47/545A61K9/5068A61K38/443A61P35/00C12Y101/03004A61K2300/00Y02A50/30
Inventor 戴箭刘雯薛巍
Owner JINAN UNIVERSITY
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