Preparation and application of nanoparticle doped RNA hydrogel for targeted triple negative breast cancer

A triple-negative breast cancer and hydrogel technology, applied in the field of biochemical nanomaterials, can solve the problem of unsatisfactory prognosis of a single microRNA, and achieve the effect of inhibiting cancer metastasis and recurrence, inhibiting growth, and having good biocompatibility.

Inactive Publication Date: 2019-10-15
LINYI UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

MicroRNAs are statistically significant in cancer treatment, but individual microRNAs are not as prognostic, study shows

Method used

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  • Preparation and application of nanoparticle doped RNA hydrogel for targeted triple negative breast cancer
  • Preparation and application of nanoparticle doped RNA hydrogel for targeted triple negative breast cancer
  • Preparation and application of nanoparticle doped RNA hydrogel for targeted triple negative breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] RNA hydrogel carriers for targeted therapy of triple-negative breast cancer, including:

[0052] (1) RNA hydrogels formed by rolling circle transcription from linear DNA transcription templates (ssDNA in Table 1),

[0053] (2) RNA hydrogel has therapeutic genes microRNA-182 and microRNA-205.

[0054] First, design a single-stranded DNA template (ssDNA in Table 1) whose two ends can be complementary to the T7 promoter (T7promotor in Table 1) primers. This single-stranded DNA contains the complementarity of each shRNA we have involved Sequence (antisense sequence of microRNA-182 and microRNA-205), a large number of copies of shRNA-182 and shRNA-205 are transcribed at low cost through rolling circle transcription as gene therapy fragments and as DOX and immune gene CpG Carrier, a multifunctional intelligent nanomedicine integrating gene therapy, chemical drug therapy and immunocombined therapy, realizes the integrated research of diagnosis and treatment of triple-negative b...

Embodiment 2

[0060] RNA hydrogel complexes for targeted therapy of triple-negative breast cancer, including:

[0061] (1) RNA hydrogels formed by rolling circle transcription from linear DNA transcription templates (ssDNA in Table 1),

[0062] (2) RNA hydrogel has therapeutic genes microRNA-182 and microRNA-205.

[0063] (3) On the RNA hydrogel, there are nucleic acid aptamers (F-C-LXLapt-Chol in Table 1), CpG fragments (CpG in Table 1) and DOX (Adriamycin);

[0064] (4) Colloidal MnO adhered by electrostatic interaction 2 @Ce6 cationic nanoparticles.

[0065] The preparation method of the RNA hydrogel complex firstly designs a straight-chain DNA transcription template, and designs antisense sequences of microRNA-182 and microRNA-205 in the straight-chain DNA, and forms a hydrogel of a pure RNA system by means of rolling circle transcription Carrier, add CpG fragments, nucleic acid aptamers and DOX, centrifuge to form RNA triple helix hydrogel, and then add colloidal MnO 2 @Ce6 cationi...

experiment example

[0074] (1) In order to determine the formation of hydrogels at each stage, we carried out transmission electron microscopy on the hydrogel products at each stage ( image 3 RNA hydrogel carrier loaded with DOX, Figure 4 Loaded with MnO 2 Hydrogel carrier of @Ce6), agarose gel electrophoresis ( figure 2 As shown, the first band is the linear DNA, the second band is the circular DNA transcription template, the third band is the rolling circle product, the fourth band is the modified CPG band, and the fifth band is the modified The band of nucleic acid aptamer, the sixth is the band of modified CPG and nucleic acid aptamer, the seventh is a 500bp marker) and particle size analyzer ( Figure 5 particle size, Figure 6 Zeta potential, where Rtrs is the transcript, Hydrogel is the hydrogel modified with nucleic acid aptamers and CpG fragments, HD is Hydrogel loaded with DOX, HDMC is Hydroge loaded with DOX and MnO 2 The characterization of the binding of @Ce6).

[0075] (2) F...

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Abstract

The invention discloses preparation and application of nanoparticle doped RNA hydrogel for targeted triple negative breast cancer. The RNA hydrogel is a pure RNA system formed in a rolling loop transcription mode, a large number of GC bonds are generated in the transcription process, a large number of sites are provided for introduction of DOX, a large number of RNA replica structures generated through rolling loop replication are polyanion aggregate, in view of strong electronegativity of the polyanion aggregate, electropositive MnO2@Ce6 nanoparticles are introduced, and the polyanion hydrogel can stabilize the colloidal positive ion MnO2@Ce6 particles, and thus enters breast cancer cells in a targeting mode for collaborative treatment. The nanoparticle doped RNA hydrogel can be used fora drug sustained release system, is good in biocompatibility, and has wide prospects in the fields such as growth inhibition effects of targeted cells, namely MDA-MB-231 tumor cells and inhibition ofcancer metastasis and recurrence.

Description

technical field [0001] The invention relates to the technical field of biochemical nanomaterials, in particular to the preparation and application of a nanoparticle-doped RNA hydrogel targeting triple-negative breast cancer, so as to realize multiple synergistic and gain-inducing treatments for triple-negative breast cancer. Background technique [0002] Breast cancer is one of the most common cancers in women, and triple-negative breast cancers (TNBCs) refer to a type of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) type. Clinical studies have proved that TNBCs is the most aggressive type of breast cancer compared with other types of breast cancer. Its prognosis is poor, and its mortality and metastasis tend to be more difficult to control. Traditional therapy includes hormone therapy, targeting the three receptors, but the therapeutic effect is not satisfactory. Therefore...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/06A61K31/704A61K31/7088A61K47/54A61P35/00A61P15/14
CPCA61K9/06A61K31/704A61K31/7088A61K41/0057A61K41/0071A61K47/549A61K47/554A61P15/14A61P35/00A61K2300/00A61K9/0024C12N15/111C12N15/87C12N2310/141C12N2320/32C12N15/113C12N15/115C12N15/85C12N2310/11C12N2310/16C12N2310/3515C12N2330/30C12N2800/00
Inventor 李雪梅刘霄凡丁来荣张书圣
Owner LINYI UNIVERSITY
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