Nano-composite of DNA tetrahedron and temozolomide

A technology of temozolomide and tetrahedron, which is applied in the field of nanocomposites of DNA tetrahedron and temozolomide, can solve the problems of drug resistance and no acquired drug resistance of temozolomide, so as to reduce drug resistance, reduce drug usage, and improve efficiency effect

Active Publication Date: 2021-03-05
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although TMZ can effectively penetrate the blood-brain barrier and target and kill glioma cells, long-term use of TMZ is prone to myelosuppression, and nearly 50% of patients will quickly develop drug resis

Method used

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  • Nano-composite of DNA tetrahedron and temozolomide
  • Nano-composite of DNA tetrahedron and temozolomide
  • Nano-composite of DNA tetrahedron and temozolomide

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1 The preparation method of the complex of the present invention

[0040] The DNA single strand with Cy5 fluorescent labeling group (only responsible for labeling), nucleic acid aptamer AS1411 and nucleic acid aptamer GS24 is formed into a tetrahedron, and the complex of the present invention is obtained after co-incubation with TMZ. The process is as follows figure 1 shown.

[0041] 1 Synthesis of DNA tetrahedron

[0042] Add four special DNA single strands at the same molar concentration to TM buffer (containing 10mM Tris-Hcl, 50mM MgCl 2 , PH=8). The solution was vortexed, centrifuged and placed in a thermal cycler. React at 95° C. for 10 minutes, then rapidly cool to 4° C. and react for 20 minutes, and the synthesis of tFNA is completed. The tFNA solution was stored in a refrigerator at 4°C.

[0043] The sequences of the four single strands involved are shown in Table 1. The corresponding relationship between the sequences in Table 1 and the sequenc...

Embodiment 2

[0065] Embodiment 2 The preparation method of the complex of the present invention

[0066] 1 Synthesis of DNA tetrahedron

[0067] With the 1.1 section of embodiment 1.

[0068] 2 Preparation of TMZ and standard curve

[0069] With the 1.2 section of embodiment 1.

[0070] 3 DNA tetrahedron combined with TMZ

[0071] The TMZ stock solution was diluted to 40 μg / ml, mixed with 250 nM tFNA (the volume ratio of TMZ and tFNA was 4:25), incubated at room temperature for 3 h at a vibration rate of 100 rpm, and then the mixture was centrifuged at 6000 rpm for 10 min to remove untreated tFNA. Combined TMZ, ie.

Embodiment 3

[0072] Embodiment 3 The preparation method of the complex of the present invention

[0073] 1 Synthesis of DNA tetrahedron

[0074] With the 1.1 section of embodiment 1.

[0075] 2 Preparation of TMZ and standard curve

[0076] With the 1.2 section of embodiment 1.

[0077] 3 DNA tetrahedron combined with TMZ

[0078] The TMZ stock solution was diluted to 60 μg / ml, mixed with 250 nM tFNA (the volume ratio of TMZ and tFNA was 4:25), incubated at room temperature at a vibration rate of 1000 rpm for 9 h, and then the mixture was centrifuged at 6000 rpm for 10 min to remove untreated tFNA. Combined TMZ, ie.

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Abstract

The invention provides a nano-composite formed by a DNA tetrahedron and temozolomide, and preferably, the nano-composite is also covalently connected with a nucleic acid aptamer AS1411 and/or a nucleic acid aptamer GS24. The invention also provides a preparation method of the composite.The method comprises the following steps of carrying out oscillation incubation on the DNA tetrahedron and the temozolomide, centrifuging, and taking the supernatant to obtain the composite The invention also provides application of the composite in preparation of anti-tumor drugs, especially anti-glioma drugs.Compared with the temozolomide, the composite has higher efficacy, can reverse the drug resistance of tumor cells to temozolomide, and has good application prospects.

Description

technical field [0001] The invention belongs to the field of antitumor drugs, in particular to a nanocomposite of DNA tetrahedron and temozolomide. Background technique [0002] DNA tetrahedral (Tetrahedral DNA, TDN), also known as tetrahedral framework nucleic acid (Tetrahedral Framework Nucleic Acid, tFNA), is an emerging nanomaterial in recent years. The DNA tetrahedron is a three-dimensional nanostructure with a tetrahedral shape that allows four DNA single strands of a specific sequence to self-assemble according to the principle of complementary base pairing under specific reaction conditions. Because tFNA has good biocompatibility, editability, low toxicity and mechanical rigidity, it has broad application prospects in the fields of biological detection, gene delivery, in vivo imaging and drug delivery. [0003] Temozolomide (TMZ) is currently the first-line targeted chemotherapy drug for the treatment of malignant glioblastoma (Glioblastoma, GBM). Although TMZ can ...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/54A61K31/4188A61K49/00A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K31/4188A61K47/549A61K47/6929B82Y5/00B82Y30/00B82Y40/00A61P35/00A61K49/0093A61K49/0052
Inventor 林云锋蔡潇潇符巍谭珺娅
Owner SICHUAN UNIV
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