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Targeted telomerase nano-drug delivery system as well as preparation method and application thereof

A nano-drug and delivery system technology, applied in drug delivery, drug combination, pharmaceutical formulation, etc., can solve the problems of lack of targeting, poor stability, easy metabolism, etc., to improve drug efficacy, good stability, and easy metabolism Effect

Pending Publication Date: 2022-05-24
宿州学院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no matter the DNA nano-drug delivery system prepared by DNA origami or DNA template combination, in terms of therapeutic applications, these multifunctional polymer DNA nanomaterials still have disadvantages such as easy metabolism, lack of targeting, and poor stability in vivo.

Method used

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  • Targeted telomerase nano-drug delivery system as well as preparation method and application thereof
  • Targeted telomerase nano-drug delivery system as well as preparation method and application thereof
  • Targeted telomerase nano-drug delivery system as well as preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0073] A preparation method of a targeted telomerase nano-drug delivery system, comprising the following steps:

[0074] S1. Design targeting telomerase hairpin DNA: Synthesize a DNA hairpin structure in which the stem portion includes G-C bases with a length of 5-8 base pairs, and the middle loop portion includes A / C bases with a length of 15-20 bases. , and label the two ends of the DNA hairpin structure with a fluorescent group-quencher group, and the concentration of the telomerase hairpin DNA is 1-2mmol / L.

[0075] S2. Preparation of targeting core: Add 1-3mM small molecule antitumor drug in dimethylformamide solution to targeted telomerase hairpin DNA, first vortex at 1500-2500 times / min for 3-5 minutes, Stir for another 10-15 hours to mix the two evenly. At this time, the small-molecule anti-tumor drug is inserted into the stem of the hairpin DNA targeting telomerase to form a DNA-small-molecule anti-tumor drug mixed solution.

[0076]S3. Preparation of the core coordi...

Embodiment 1

[0083] The embodiment of the present application discloses a targeted telomerase nano-drug delivery system, comprising Fe 2+ , Targeting telomerase hairpin DNA, DOX, tannic acid, PEG-dopamine.

[0084] The 5'-end of the telomerase-targeting hairpin DNA is base-paired with the 3'-end para-G-C to form a stem, and the length of the stem is 7 base pairs. The 3' end starts with telomerase TTAGGG and is combined with a telomerase primer, which is 5'-AATCCCACCACCACCTCC-3'. The middle loop portion of the hairpin DNA is A / C base, and the middle loop portion is 15 bases in length. The 5' end of the hairpin DNA is labeled with a fluorophore 6-FAM, and the 3' end is labeled with a quenching group DABCYL. The hairpin structure of the target telomerase hairpin DNA molecular beacon designed in this example is 5'-6-FAM-TGGGATTGGGCGGGAAAAAAAAAAAAAACCCGCCCAATCCCAGGAGTGGTGGTGGGATT-DABCYL-3'.

[0085] DOX is loaded in the stem of the stem hairpin DNA, Fe 2+ Coordinate with the middle loop of ...

Embodiment 2

[0087] The embodiment of the present application discloses a preparation method of a targeted telomerase nano-drug delivery system, comprising the following steps:

[0088] S1. Design targeting telomerase hairpin DNA: Synthesize a DNA hairpin structure with a G-C base with a stem length of 7 base pairs and an A / C base with a middle loop length of 15 bases, and at 5 The '-end labeled 6-FAM and the 3'-end labeled DABCYL were used to synthesize the targeting telomerase DNA molecular beacon hairpin, and the concentration was 1.5 mmol / L.

[0089] S2. Preparation of targeting core: Add 100 μL (1 mM) DOX solution in dimethylformamide to 500 mL targeted telomerase hairpin DNA, first vortex at 2000 times / min for 3 minutes, and then stir for 12 hours to make The two are mixed evenly, and DOX is inserted into the stem of the telomerase-targeting hairpin DNA to form a DNA-DOX mixed solution.

[0090] S3. Preparation of core coordination solution: in Fe 2+ Add 30-80 μL (15 mmol / L) FeCl t...

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Abstract

The invention relates to the technical field of anti-tumor nano-drugs, in particular to a targeted telomerase nano-drug delivery system which comprises metal ions with coordination capacity, targeted telomerase hairpin DNA, a small-molecule anti-tumor drug, a polyphenol compound and an in-vivo imaging tracer. The stem part of the hairpin DNA is a G-C basic group of 5-8 basic group pairs and is used for loading a small-molecule anti-tumor drug; the middle ring part is an A / C basic group with 15-20 basic groups and is coordinated with metal ions; fluorophore-quenching groups are arranged at two ends; the metal ions are coordinated with the hairpin DNA-micromolecular antitumor drug, the polyphenol compound and the in-vivo imaging tracer agent to form an inner core, a surface and a periphery of the nano-drug delivery system. The nano-drug delivery system has targeting property, high drug loading capacity and good stability, the drug effect of the micromolecular antitumor drug is improved, the polyphenol and the micromolecular antitumor drug also have a synergistic drug effect, synchronous treatment of molecular imaging diagnosis and targeted chemotherapy is realized, and the purpose of precise treatment of malignant tumors is achieved.

Description

technical field [0001] The invention relates to the technical field of anti-tumor nano-drugs, in particular to a targeting telomerase nano-drug delivery system and a preparation method and application thereof. Background technique [0002] Malignant tumors, as a harmful and intractable disease, have always been the focus of research in various fields of life sciences. Currently, there are still three intractable problems in the treatment of tumors: tumor drug resistance, tumor metastasis and tumor progression. Microenvironment. As biologists continue to conduct in-depth research on malignant tumors, it is found that gene mutation signaling pathways are not only related to the occurrence of malignant tumors, but also related to metastasis and chemical drug resistance in tumor treatment. [0003] Anthracyclines, such as doxorubicin, epirubicin, and daunorubicin, are widely used chemotherapeutic drugs for cancer treatment, which can directly treat cancer. However, due to its ...

Claims

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Application Information

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IPC IPC(8): A61K47/54A61K47/52A61K9/51A61K45/00A61K49/00A61P35/00
CPCA61K47/549A61K45/00A61K47/52A61K49/0093A61K49/0052A61P35/00A61K9/5123
Inventor 单玲玲赵芳卢一飞徐冲吴雷
Owner 宿州学院
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