Nucleic acid nano-drug carrier as well as preparation method and application thereof

A nucleic acid nanotechnology and drug technology, applied in the field of nanomedicine, can solve the problems of large toxic and side effects of chemotherapy drugs, short blood circulation time, and high dosage, so as to promote the maturation of dendritic cells, kill and remove tumors, and inhibit cell viability. Effect

Pending Publication Date: 2022-03-15
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, traditional chemotherapeutic drugs have poor water solubility, low tumor specificity and short blood circulation time, which will cause large toxic side effects, high dosage and long treatment cycle of chemotherapeutic drugs
In addition, studies have shown that some chemotherapy drugs promote tumor immune escape mechanisms, which also increase the risk of cancer recurrence and metastasis

Method used

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  • Nucleic acid nano-drug carrier as well as preparation method and application thereof
  • Nucleic acid nano-drug carrier as well as preparation method and application thereof
  • Nucleic acid nano-drug carrier as well as preparation method and application thereof

Examples

Experimental program
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Embodiment 1

[0102] This embodiment provides a nucleic acid nano-drug carrier, which is prepared by the following preparation method:

[0103] (1) Preparation of DNA-RGD complex:

[0104] The DNA-RGD complex is obtained by a click reaction, in which the azide is modified at the 5' end of the DNA, that is, N3-TTTTAAACTCTTTGCGCAC; The reaction is carried out under the catalysis of divalent copper catalyst Cu(II)-TBTA complex;

[0105] The specific steps are as follows: the azide-modified DNA (N 3 -TTTTAAACTCTTTGCGCAC) and alkyne-modified RGD polypeptide (c(RGDfK)-GG-propargylglycine) were dissolved in PBS buffer to prepare 200 μM DNA stock solution and 400 μM RGD polypeptide stock solution; ascorbic acid was dissolved in water to prepare 10mM stock solution;; Mix 200μL DNA stock solution, 400µL RGD stock solution, 200µL DMSO, 200µL Cu(II)-TBTA complex (10mM) and 200µL ascorbic acid in a 1.5mL centrifuge tube, incubate at room temperature in the dark 12h, separated and purified by polyacry...

Embodiment 2

[0136] This embodiment provides a nucleic acid nano-drug carrier. The difference from Example 1 is that in the synthesis of the nucleic acid nano-drug carrier, the RGD polypeptide is replaced by a GPR polypeptide. In addition, other raw materials, preparation methods and reactions The conditions were the same as in Example 1, so as to prepare a nucleic acid nano drug carrier based on chemotherapy-immunotherapy combined treatment of tumors.

Embodiment 3

[0138] This embodiment provides a nucleic acid nano-drug carrier. The difference from Example 1 is that in the synthesis of the nucleic acid nano-drug carrier, the RGD polypeptide is replaced by the TAT polypeptide. In addition, other raw materials, preparation methods and reactions The conditions were the same as in Example 1, so as to prepare a nucleic acid nano drug carrier based on chemotherapy-immunotherapy combined treatment of tumors.

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Abstract

The invention provides a nucleic acid nano-drug carrier as well as a preparation method and application thereof. The nucleic acid nano-drug carrier comprises a DNA origami nano-structure, a cholesterol-disulfide bond-DNA compound, a tumor targeting peptide-DNA compound and a drug, and the origami structure contains a response element DNA molecular lock modified with a disulfide bond. The nucleic acid nano-drug carrier provided by the invention can deliver a chemotherapeutic drug to a tumor site in a targeted manner, responds to a tumor environment, opens the carrier to release the chemotherapeutic drug, reduces toxic and side effects of the chemotherapeutic drug on normal tissues and organs, triggers tumor cell immunogenic cell death, and activates anti-tumor immunity. And by combining with an immune checkpoint antibody, the aim of better treating tumors is fulfilled.

Description

technical field [0001] The invention belongs to the technical field of nanomedicine, and in particular relates to a nucleic acid nanomedicine carrier and a preparation method and application thereof. Background technique [0002] Cancer is one of the major diseases that threaten human life and health and cause human death worldwide. Chemotherapy is one of the main methods to treat cancer by inhibiting the proliferation, invasion and metastasis of cancer cells through the application of cytotoxic chemical drugs, and finally destroying cancer cells. However, traditional chemotherapeutic drugs have poor water solubility, low tumor specificity and short blood circulation time, which will cause severe side effects, high dosage and long treatment cycle of chemotherapeutic drugs. In addition, studies have shown that some chemotherapy drugs can promote tumor immune escape mechanisms, which can also increase the risk of cancer recurrence and metastasis. [0003] The emergence of na...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/54A61K47/62A61K31/337A61K31/4745A61K47/26A61P35/00B82Y5/00
CPCA61K47/6949A61K47/62A61K47/554A61K31/4745A61K31/337A61K47/26A61P35/00B82Y5/00A61K2300/00
Inventor 丁宝全王一鸣蒋乔
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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