Preparation method and application of realgar nanoparticles

A nanoparticle, realgar technology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of limited clinical application, low bioavailability, insoluble in water, etc., to prolong the residence time in the body and reduce toxic and side effects. , the effect of maximizing the curative effect

Active Publication Date: 2020-11-20
CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But As 4 S 4 It is extremely difficult to dissolve in water, has poor druggability, low bioavailability, and high toxicity, which limits its clinical application

Method used

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  • Preparation method and application of realgar nanoparticles
  • Preparation method and application of realgar nanoparticles
  • Preparation method and application of realgar nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] A realgar nanoparticle, comprising realgar and bovine serum albumin.

[0040] The nano-realgar compound drug of the present embodiment is prepared by the following method:

[0041] Will As 4 S 4 Dissolve it in ethylenediamine at a concentration of 20 mg / mL, sonicate for 15 minutes, centrifuge at 15,000 rpm for 5 minutes, and take the supernatant. 2mLAs 4 S 4 Disperse the supernatant in 8mL of water, add 3ml of 20mg / ml BSA solution, stir for 5min, add 7mL of 4MHCl, stir for 30min, and dialyze in water for 8h with a dialysis bag with MWCO=3500Da to obtain realgar nanoparticles: As 4 S 4 @BSA NPs.

Embodiment 2

[0043] A kind of realgar nanoparticles, including realgar, bovine serum albumin and folic acid.

[0044] The realgar nanoparticles of the present embodiment are prepared by the following method:

[0045] (1) According to the molar ratio of FA, EDC, and NHS: 1:2:1, it was dissolved in DMSO and stirred for 30 minutes in the dark to obtain FA with a concentration of 25 mg / ml. Slowly add the FA solution into the BSA carbonate buffer solution dropwise, stir at room temperature for 24 hours, dialyze in PBS (10mm, pH=7.4) with a dialysis bag of MWCO=3500Da for 2 days, dialyze in water for 1 day, collect and lyophilize to obtain BSA -FA.

[0046] (2) As 4 S 4 Dissolve it in ethylenediamine at a concentration of 20 mg / mL, sonicate for 15 minutes, centrifuge at 15,000 rpm for 5 minutes, and take the supernatant. At the same time, 60 mg of lyophilized BSA-FA was dissolved in 3 ml of ultrapure water, and then 2 mL of As 4 S 4 Disperse the supernatant in 8mL of water, slowly add BSA-...

Embodiment 1 and Embodiment 2

[0054] Example 1 and Example 2 The cytotoxicity of realgar nanoparticles to human chronic myelogenous leukemia cell K562:

[0055] (1) The logarithmic growth K562 cells were taken, diluted with IMDM medium containing 10% fetal bovine serum to a cell suspension with a density of 50000 cells / mL, and inoculated into a 96-well culture plate at 100 μL per well. In a carbon dioxide incubator (37°C, 5% CO 2 , saturated humidity) after culturing for 2 h, the culture medium was discarded by centrifugation.

[0056] (2) Add 100 μL of As diluted to different concentrations with culture medium to each well 4 S 4 @BSA-FA, As 4 S 4 @BSA (concentration in As 4 S 4 Concentration meter, respectively 0, 0.5, 1, 5, 10, 20, 50μg / ml), the same concentration was repeated for 6 replicate wells, and incubated for 48h.

[0057] (3) Centrifuge to remove the medium, add 100 μL of MTT solution (0.5 mg / mL, diluted in IMDM) to each well, continue to incubate for 4 hours, terminate the culture, and d...

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Abstract

The invention provides a preparation method and application of realgar nanoparticles. The realgar nanoparticles mainly comprise As4S4, BSA and FA. The preparation method comprises the following steps:by taking an As4S4-ethylenediamine molecular cluster solution as a precursor, carrying out nucleation growth on As4S4 under the stability of BSA by utilizing an acid-base reaction, thereby forming the nanoparticles. The realgar nanoparticles can be further subjected to targeting ligand modification, and the targeting property and the treatment index of tumor cells are increased. The realgar nanoparticles provided by the invention can down-regulate the BCR-ABL protein level, induce apoptosis of chronic granulocytic leukemia cells from a mitochondrial pathway, and reduce potential toxic and side effects.

Description

technical field [0001] The invention relates to the field of nanobiology technology, in particular to a preparation method and application of realgar nanoparticles. Background technique [0002] Chronic myeloid leukemia (CML) is a malignant clonal proliferative hematopoietic disease originating from pluripotent hematopoietic stem cells in bone marrow, accounting for 15-20% of all leukemias. Genetic studies have shown that more than 95% of CML patients have a Philadelphia chromosome (ph), and its pathogenesis is formed by the mutual translocation of the proto-oncogene abl on chromosome 9 and BCR (broken cluster region) on chromosome 22 t(9;22)(q34;q11), according to the BCR gene break site, can form three bcr-abl fusion proteins: p210, p230, p190. BCR-ABL fusion protein is an abnormal receptor tyrosine kinase (PTK), which can significantly increase the phosphorylation level of specific substrate protein molecules downstream of the signal transduction pathway. Under normal ci...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/36A61K47/54A61K47/64A61P35/02B82Y5/00
CPCA61K33/36A61K47/643A61K47/545A61P35/02B82Y5/00
Inventor 周文虎李辉余梦真刘炫均王胜玫
Owner CENT SOUTH UNIV
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