Graphdiyne derivatives capable of treating leukemia

A technology of graphyne and derivatives, applied in the field of biomedicine, can solve problems such as effective concentration multidrug resistance, tumor drug concentration not reaching, drug aggregation, etc.

Active Publication Date: 2020-11-17
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] One of the most common ways to treat leukemia is chemotherapy, but there are a series of problems in chemotherapy, such as the accumulation of drugs in normal tissues, the concentration of tumor drugs cannot reach the effective concentration, and multidrug resistance, etc.

Method used

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  • Graphdiyne derivatives capable of treating leukemia
  • Graphdiyne derivatives capable of treating leukemia
  • Graphdiyne derivatives capable of treating leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Graphdiyne and graphdiyne oxide were ultrasonically dispersed in ultrapure water at a concentration of 10 mg / mL. Detect the relevant properties of graphyne and graphyne oxide: including overall size (transmission electron microscope), hydrodynamic size and Zeta potential (particle size potential analyzer). Graphdiyne and graphdiyne oxide were dispersed in ultrapure water at a concentration of 10 mg / mL. see results figure 1 with table 1.

[0030] Table 1 Characterization results of graphyne and graphyne oxide

[0031] TEM particle size (μm) Hydrated particle size (nm) Zeta potential (mV) graphyne 82.11±21.57 104.1±69.98 -17.5±6.23 graphyne oxide 85.65±16.53 117.56±81.18 -32.4±8.95

Embodiment 2

[0033] α-MEM (purchased from Gibco, product number A1049001) and FBS (purchased from Gibco, product number 10100147) were prepared according to the volume ratio of 80:20, and stored at -4°C until use.

[0034] After OCI-AML3 and OCI-AML2 cells were recovered from liquid nitrogen, the above medium was used at 10 per ml 6 The proportion of cells was inoculated and cultured, subcultured once every 3 days, and the cells entered the logarithmic growth phase to start subsequent experiments.

Embodiment 3

[0036] Take logarithmic growth OCI-AML3 and OCI-AML2 cells, after centrifugation and counting, resuspend the cells with medium to 10 5 / mL, 100 μL per well was planted into a 96-well plate, and different concentrations of graphyne and graphyne oxide were added respectively. After incubation for 24 hours, the cell viability was measured by the CCK-8 method. The results are shown in figure 2 .

[0037] Experimental group:

[0038] Group: graphyne, graphyne oxide;

[0039] Concentration: negative control (0), 10, 20, 30, 40, 50 μg / mL;

[0040] Cell type: OCI-AML3, OCI-AML2, HSPC;

[0041] Co-incubation time: 24h.

[0042] Three replicate wells were performed in each group, and the average value was taken as the final result.

[0043] Add graphyne and graphyne oxide to twice the corresponding working concentration and the prepared medium in Example 2, add 100 μL of mixed solution to each well, and gently blow the cells away. At this time, graphyne and graphyne oxide are the ...

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Abstract

The invention provides an application of a two-dimensional carbon-based nano material in killing leukemia cells. The two-dimensional carbon-based nano material comprises graphdiyne (GDY), graphdiyne oxide (GDYO) and other graphdiyne derivatives. The leukemia cells are an acute myeloid leukemia (AML) cell line which is mutated by DNMT3A. The GDY and the GDYO are of nanosheet layer structures, the size ranges from 50 nm to 500 nm, the GDY and the GDYO are added into different types of AML cells cultured in vitro according to a certain dosage or injected into an AML mouse model body, specific killing only for DNMT3A mutant cells can be achieved, and no obvious influence is caused on normal cells. The graphdiyne derivatives have great application potential in the clinical and scientific research fields of research and development of anti-leukemia drugs, drug effect research, leukemia cell drug resistance research and the like.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to the application of a two-dimensional carbon-based nanometer material to specifically kill DNMT3A mutant acute myeloid leukemia cells in in vitro culture and mouse models. Background technique [0002] Among the malignant tumor mortality rates in my country, leukemia ranks first among children and adults under the age of 35, causing immeasurable losses to patients' families and society. Among all leukemia types, acute myeloid leukemia (AML) has the highest incidence rate (1.62 / 100,000). AML is a group of clonal hematopoietic diseases (Clonal Hematopoiesis, CH) originating from myeloid hematopoietic stem cells. It is mainly characterized by abnormal differentiation and malignant proliferation of myeloid primitive cells in bone marrow and peripheral blood, which inhibit normal hematopoiesis. Its clinical manifestation is anemia , bleeding, infiltration and infection. Based on the...

Claims

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Application Information

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IPC IPC(8): A61K33/44A61P35/02
CPCA61K9/0019A61K33/44A61P35/02
Inventor钱鹏旭王琪炜韩颖丽
OwnerZHEJIANG UNIV