Application of carbonyl iron-sulfur cluster compound nanoparticles in drug preparation

A nanoparticle and nanomedicine technology, applied in the field of nanomedicine, can solve the problems of toxicity, the treatment effect of malignant tumors needs to be improved, and achieve the effect of less toxic and side effects

Active Publication Date: 2020-06-16
SHANGHAI NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the therapeutic effect of pure chemodynamic therapy on malignant tumors still needs to be improved.
[0004] CO produced by heme oxygenase at low concentrations in living organisms has cytoprotective activity and, conversely, at very high concentrations is extremely toxic due to its accumulation in tissues

Method used

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  • Application of carbonyl iron-sulfur cluster compound nanoparticles in drug preparation
  • Application of carbonyl iron-sulfur cluster compound nanoparticles in drug preparation
  • Application of carbonyl iron-sulfur cluster compound nanoparticles in drug preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] C 8 h 4 Fe 2 o 6 S 2 -Chemical kinetic experiment of PSMA-PEG NPs in response to hydrogen peroxide

[0059] (1) Effects of different pH values: acetic acid-sodium acetate system is used as a buffer solution, and 3,3',5,5'-tetramethylbenzidine (TMB) is used as an indicator for detecting hydroxyl radicals ( OH) , add acetic acid-sodium acetate (0.1M, pH=7.4, pH=5.2), C 8 h 4 Fe 2 o 6 S 2 -PSMA-PEG NPs (50μM, calculated based on the concentration of Fe), TMB solution (0.3mM), H 2 o 2 Solution (0.1mM), the total volume of the above solution is 3mL, mix it evenly and place it in a water bath at 37°C for 50min, and test the absorbance of the mixed solution, as shown in Image 6 shown.

[0060] The tumor microenvironment is a slightly acidic environment (pH=5.2), while the normal tissue is a neutral environment (pH=7.4). Depend on Image 6 It can be seen that at pH=5.2, C 8 h 4 Fe 2 o 6 S 2 -PSMA-PEG NPs can react with hydrogen peroxide to generate OH,...

Embodiment 2

[0081] C 8 h 4 Fe 2 o 6 S 2 -PSMA-PEG NPs cell experiment

[0082] (1) Cytotoxicity evaluation: mouse melanoma (B16-F10) cells and human umbilical vein endothelial cells (HUVEC) were selected. Take the logarithmic phase cells, digest with trypsin, collect by centrifugation after termination, and make the cell concentration 5×10 4 cells / mL cell suspension, according to this, add 100 μL of cell suspension to each well of the 96-well plate, and incubate in a 37°C incubator for 12 hours, so that the cells are fully adhered to the wall, and the material is mixed with high glucose medium (DMEM). Dilute to concentrations of clusters: 0, 20, 40, 100, 200, 400 μM C 8 h 4 Fe 2 o 6 S 2 - PSMA-PEG NPs solution. Take 100 μL of prepared nanomaterials with different concentrations and add them to a 96-well plate (5 parallel wells are set at every concentration), and put the 96-well plate into an incubator to continue incubation for 12 or 24 hours. After incubation, suck out...

Embodiment 3

[0090] In Vivo Therapeutic Experiments

[0091] The treatment was divided into two groups: (1) Control group (Saline) and (2) Treatment group (MNPs), the concentration of the material injected into the mice was 1.4mM (calculated by cluster concentration), that is, 5.21mg / kg . Taking the time of intravenous injection of mouse B16-F10 cells as the starting point, denoted as D0, the mice were intravenously injected with nanomaterials on the fourth day for treatment experiments, followed by the second treatment on the seventh day, and on the 10th day. The third treatment was carried out on the 13th day, the fourth treatment was carried out on the 13th day, and the treatment was terminated on the 16th day. Before each injection of nanomaterials (on the 4th, 7th, 10th, 13th, and 16th days), a mouse was dissected, its lungs were taken out, the weight of the lungs was weighed, and photos were taken. The body weight of the mice was monitored, and the results were as follows: Figu...

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Abstract

The invention belongs to the technical field of nano medicine, and discloses an application of carbonyl iron-sulfur cluster compound nanoparticles in drug preparation, in particular to application ofcarbonyl iron-sulfur cluster compound nanoparticles (C8H4Fe2O6S2-PSMA-PEG NPs) in preparation and screening of medicine for treating/preventing melanoma pulmonary metastasis. The nanoparticles have aspherical structure taking a carbonyl iron-sulfur cluster compound (C8H4Fe2O6S2) as a core and taking an amphiphilic block polymer (PSMA-PEG) as a coating layer; by means of the synergistic effect ofchemical dynamics and CO gas treatment in a special microenvironment in a tumor, melanoma pulmonary metastasis is accurately treated, and the treatment effect is remarkable.

Description

technical field [0001] The invention belongs to the technical field of nanomedicine, in particular to a carbonyl iron-sulfur cluster nanoparticle (C 8 h 4 Fe 2 o 6 S 2 -PSMA-PEG NPs), its preparation method and its application in the preparation and screening of drugs for the treatment / prevention of melanoma lung metastasis. Background technique [0002] At present, there are 100 different types of human cancers known. Malignant melanoma is the most aggressive type of malignant tumors. Generally, local recurrence will not occur, but local and distant metastasis, especially lung metastasis, may occur. However, the current treatment methods chemotherapy and radiotherapy are not ideal for this kind of metastasis, and the side effects are relatively large. Many malignant melanoma patients die of tumor metastasis. Importantly, the treatment and prevention of melanoma metastasis are still major challenges, and with the development of nanotechnology, there is an urgent need to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K31/555A61K33/00A61P35/00A61P35/04C12Q1/02
CPCA61K9/5146A61K31/555A61K33/00A61P35/00A61P35/04G01N33/5011C12N2503/02G01N2500/10A61K2300/00
Inventor 杨红翟田莉宋云鹏
Owner SHANGHAI NORMAL UNIVERSITY
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