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Oxygen consumption type inorganic nano-enzyme treatment reagent as well as preparation method and application thereof

A therapeutic reagent and inorganic nanotechnology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of unrealizable process simplification and large-scale preparation, achieve precise and specific tumor treatment, prevent recurrence and metastasis, well-structured effect

Pending Publication Date: 2022-07-22
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] CcO-like inorganic nanozymes are still in the initial stage of research, and the reported CcO-like inorganic nanozymes are all single-atom nanozymes with complex synthetic structures and preparation processes, which cannot achieve process simplification and large-scale preparation process requirements

Method used

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  • Oxygen consumption type inorganic nano-enzyme treatment reagent as well as preparation method and application thereof
  • Oxygen consumption type inorganic nano-enzyme treatment reagent as well as preparation method and application thereof
  • Oxygen consumption type inorganic nano-enzyme treatment reagent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Synthesis of AQ4N@Cu-Ag NPs

[0050] Step (1), add silver nitrate solution (1mL, 0.2M), copper nitrate solution (1mL, 0.1M) and polyvinylpyrrolidone K15 solution (100mL, 5g / L) into a 500mL beaker, stir at room temperature for 30min and mix well to obtain Mixed solution, add the hydrazine hydrate mixed solution containing L-ascorbic acid and sodium hydroxide to the mixed solution (consisting of 100mL concentration of 50mM L-ascorbic acid aqueous solution, 100mL concentration of 5g / L sodium hydroxide aqueous solution and 30μL concentration of 35wt% Mixed with hydrazine hydrate), reacted at room temperature for 10 min, centrifuged, washed three times with absolute ethanol, and dried to obtain copper-silver alloy nanoparticles (Cu-AgNPs), which were brown-gray solid powder; SEM image of Cu-Ag NPs and transmission electron microscope images, see figure 1 and figure 2 , indicating that the Cu-Ag NPs exhibit a porous spherical shape, and the size of the synthesized Cu-Ag NP...

Embodiment 2

[0054] Cu-Ag NPs consume O 2 performance

[0055] A portable dissolved oxygen meter was used to test the ability of nanoparticles to catalyze oxygen consumption under different conditions. The test was divided into 5 groups: the first group was the blank control group, which was 10 mL of deionized water; the second group was the Cytc control group, which was 10 mL of the Cytc solution ( The concentration was 10 μg / mL, prepared with deionized water, and the pH value was 6.75); the third group was the Cu-Ag NPs control group, which was 10 mL of Cu-Ag NPs dispersion (concentration of 100 μg / mL, prepared with deionized water, The pH value is 6.75); the fourth group is the Cu-Ag+Cytc control group, 10 μL Cytc (10 mg / mL) was added to 10 mL Cu-Ag NPs dispersion (concentration 100 μg / mL, prepared with deionized water, pH value was 7.35, simulating the neutral environment of normal tissue); the fifth group was the Cu-Ag+Cytc group, 10 μL Cytc (10 mg / mL) was added to 10 mL Cu-Ag NPs di...

Embodiment 3

[0069] Apoptosis test of AQ4N@Cu-Ag NPs

[0070] In order to explore the apoptosis mechanism of AQ4N@Cu-Ag NPs, 4T1 breast cancer cells were tested by flow cytometry. @Cu-AgNPs dispersion, Cu-Ag NPs dispersion with a concentration of 100 μg / mL, and AQ4N solution with a concentration of 100 μg / mL; 4T1 breast cancer cells were grown in a hexagonal medium containing 2 mL of 1640 medium at 37 °C with 5% carbon dioxide. After incubation in the well plate for 24 hours, 4T1 breast cancer cells were treated differently: i) blank control group (Control): 100 μL of pH 7.4 phosphate buffer was added; ii) the first treatment group (AQ4N): 100 μL of 100 μg / mL AQ4N solution; iii) the second treatment group (Cu-AgNPs): add 100 μL 100 μg / mL Cu-Ag NPs dispersion; iv) the third treatment group (AQ4N@Cu-Ag NPs): add 100 μL 100 μg / mL AQ4N @Cu-Ag NPs dispersion. The 4T1 breast cancer cells were further incubated at 37°C with 5% carbon dioxide for 24 hours, and the dead cells were stained with pr...

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Abstract

The invention discloses a CcO-imitated inorganic nano-enzyme treatment reagent which is an AQ4N-coated Cu-Ag nano-material formed by taking copper-silver alloy nano-particles as a carrier, loading a hypoxia activated chemotherapeutic drug AQ4N in pores of the copper-silver alloy nano-particles and modifying the surfaces of the copper-silver alloy nano-particles with hydrophilic aminated polyethylene glycol. The invention also discloses an application of the simulated CcO inorganic nano-enzyme treatment reagent in preparation of hunger therapy / active oxygen therapy / chemotherapy synergistic tumor therapy drugs. The mimic CcO inorganic nano-enzyme treatment reagent is clear in structure and simple in synthesis process, has enzyme-like activity, can cooperate with cancer cell endogenous overexpressed Cytc to reduce oxygen and effectively improve the oxygen concentration of a tumor microenvironment, and can be efficiently enriched at a tumor site to generate a hunger effect, cut off energy supply and generate toxic active oxygen species, so that the treatment effect is remarkable. And AQ4N is activated to generate AQ4 to kill tumor cells, so that recurrence and metastasis of tumors are effectively prevented.

Description

technical field [0001] The invention belongs to the field of nano-medicine, and relates to an oxygen-consuming inorganic nano-enzyme therapeutic reagent and a preparation method thereof, and the application of the oxygen-consuming inorganic nano-enzyme reagent in the preparation of synergistic anti-tumor drugs. Background technique [0002] At present, chemotherapy is still the mainstream treatment in the field of cancer treatment. Recently, a class of small-molecule hypoxia-activated chemotherapeutics has been clinically developed, which can effectively utilize the condition of insufficient local oxygen at the tumor site to activate chemotherapeutic drugs to produce toxicity, thereby specifically killing cancer cells. Toxic side effects of normal cells, reducing possible complications of chemotherapy. For example, AQ4N (banoxantronedihydrochloride), a class of hypoxia-activated prodrugs that have been used clinically, is not toxic by itself and can remain stable in an envi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/38A61K47/60A61K47/69A61P35/00A61P35/04B82Y5/00B82Y40/00B22F9/24B22F1/054B22F1/18A61K33/34A61K31/14
CPCA61K33/38A61K33/34A61K31/14A61K47/60A61K47/6935A61K9/0019A61P35/00A61P35/04B82Y5/00B82Y40/00B22F9/24A61K2300/00Y02A50/30
Inventor 董晓臣曹长宇宋雪娇杨楠邵进军
Owner NANJING UNIV OF TECH
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