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Application of gold nanocages in DAN injury resistance

A DNA damage and gold nanocage technology is applied in the field of biomedical material technology and biomedicine, which can solve the problems of high side effects, inability to quickly and efficiently remove free radicals, lack of specificity, etc., and achieve increased cell activity and good Effects on Biosecurity, Facilitating Quantity and Function

Inactive Publication Date: 2019-09-06
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The current approach against DNA damage is mainly the use of inhibitors of pathways related to the DNA damage response, such as polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, ataxia telangiectasia mutations / ataxia telangiectasia Rad3-associated protein (ATM / ATR) kinase inhibitors, DNA-dependent protein kinase (DNA-PKcs) inhibitors, checkpoint kinase (Chk1 / 2) inhibitors, cyclin-dependent kinase (CDK) inhibitors and DNA alpha Methyltransferase (MGMT) inhibitors, etc., or oxygen free radical scavengers (such as W2721), anti-inflammatory drugs (such as glucocorticoids), cytokines (such as G-CSF), however, these inhibitors generally act on protein Kinases may act on all cells through the phenomenon of synergistic lethality, while hormonal drugs have relatively large side effects, lack of specificity, and have certain destructive power on normal tissues and cells, and these drugs cannot quickly and efficiently remove a large amount of DNA damage produced by the body. Free radicals, also have certain drug resistance
[0004] With the rapid development of the field of nanomaterials, various types of nanomaterials have shown good application prospects in the prevention, treatment and targeted drug delivery of tumors, but no nanomaterials can resist various types of DNA damage. and scavenging reactive oxygen species in cells and promoting cell anti-aging

Method used

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  • Application of gold nanocages in DAN injury resistance
  • Application of gold nanocages in DAN injury resistance
  • Application of gold nanocages in DAN injury resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The preparation method of embodiment 1 gold nanocage

[0038] The present invention proves the application of gold nanocages in resisting DNA damage and death. The gold nanocages are cubic nanocage structures with hollow inside and porous side walls. The average diameter of the particles is between 50-120nm, preferably 70- 100nm, the particle size is uniform, and its shape under the transmission electron microscope is as follows figure 1 ; In the near-infrared region (wavelength 700-900nm), there is a characteristic peak absorption, preferably 780-810nm, and its ultraviolet absorption peak is as figure 2 .

[0039] Gold nanocages are synthesized by electrochemical substitution method, including the following steps:

[0040] 1) Heat 50mL of ethylene glycol to 150 degrees under magnetic stirring, then add 0.6mL of 3.0mM Na 2 S. After 2 minutes, PVP solution in ethylene glycol (20 mg / mL, 12.5 mL) and hydrochloric acid solution (3.0 mM, 5 mL) were added rapidly. After...

Embodiment 2

[0047] Example 2 Gold nanocages promote the proliferative activity of cells

[0048] DNA damage can be caused by DNA metabolism, chemical drug (reagent) mutagenesis, ionizing radiation and reactive oxygen damage. DNA damage directly affects DNA replication, transcription and protein synthesis, and then affects life activities such as cell growth, development, inheritance, metabolism and reproduction. In order to study whether gold nanocage materials can protect cell growth activity under different drug stimuli , we treated RAW264.7 cells with different concentrations of hydroxyurea and low-glucose medium to induce cell damage, by adding the gold nanocage material synthesized in Example 1, and using commercially available gold nanorod material (Deco island gold, DKAU- 5.4) As a control, the CCK8 assay was used to detect the effect of different nanomaterials on the cell proliferation activity.

[0049] experimental method:

[0050] First, mononuclear cells RAW264.7 (mouse-deri...

Embodiment 3

[0052] Example 3 Gold nanocage material reduces apoptosis caused by DNA damage and its mechanism

[0053] In order to verify the rescue effect of gold nanocages on cell damage, we further used hydroxyurea to induce DNA damage state to study the effect of gold nanocages on cell apoptosis.

[0054] Experiment 1: Changes in cell apoptosis detected by flow cytometry

[0055] (1) Cell treatment: first seed RAW264.7 cells in a 6-well cell culture plate and culture them with 10% FBS at 37°C and 5% CO 2 Cultivate in the incubator for 4 hours, and then replace with the medium containing 0.5mM hydroxyurea; at the same time, add 10 μg / mL of the gold nanocage material synthesized in Example 1 to the experimental group, and add an equal volume of double-distilled water to the control group. In order to study the effect of gold nanocages on short-term damage resistance and long-term induction repair of cells, the experimental group was divided into two groups: ① test after 12 hours of cult...

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Abstract

The invention discloses application of gold nanocages in DAN injury resistance. Experiments prove that the gold nanocages help relieve cellular DNA injury induced by active oxygen, chemotherapeutic drugs (such as hydroxyurea) and physical irradiations (such as ultraviolet and X-ray); in manifesting, the gold nanocages promote proliferative activity of cells with DNA injury and inhibit apoptosis ofcells caused by DNA injury; the gold nanocages can evidently inhibit fibroblast apoptosis caused by ultraviolet irradiation and are applicable to the preparation of anti-aging or anti-radiation cosmetics; the gold nanocages as drug carriers feature optothermal release, never stay in the body for long time, and have good biosafety; X-ray irradiation for a mouse model verifies that the gold nanocages can promote reconstruction of the bone marrow blood-producing system, maintain the steady state of the immune system and extend the survival rate, and are applicable to the preparation of drugs toprevent and treat radiation-caused marrow injury or drugs to treat aplastic anemia.

Description

technical field [0001] The invention belongs to the field of biomedical material technology and biomedicine, and specifically relates to the application of gold nanocage materials in anti-DNA damage, reduction of cell apoptosis and prevention and treatment of bone marrow damage. Background technique [0002] DNA is the most important genetic material in the life activities of the body, and the maintenance of its molecular structure integrity and stability is of great significance to the survival of cells and the normal physiological activities. However, DNA always faces invasion from inside or outside the organism. DNA damage generally occurs in the life activities of cells, which may lead to cell mutation, cancer and even death. DNA damage can be caused by DNA metabolism, chemical drug (reagent) mutagenesis, ionizing radiation and reactive oxygen damage. DNA damage directly affects DNA replication, transcription and protein synthesis, and further affects life activities su...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/242A61K41/00A61K47/02A61P39/00A61P39/06A61P7/00A61P7/06A61P37/02A61K8/19A61Q19/08A61Q17/04
CPCA61K8/19A61K33/242A61K41/0042A61K41/0052A61K47/02A61P7/00A61P7/06A61P37/02A61P39/00A61P39/06A61Q17/04A61Q19/08
Inventor 张玉峰时缪斯赵彦兵边专理查德·米勒
Owner WUHAN UNIV
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