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Nanoparticle targeting breast cancer cell and lymph node metastasis focus, preparation method and application

A technology for lymph node metastasis and breast cancer cells, which is applied in the field of preparation and dual-targeting of nanoparticles of breast cancer cells and their lymph node metastases, can solve the problems of low reliability of identification of breast cancer lymph node metastasis, and achieves good labeling effect and improved The effect of accuracy

Active Publication Date: 2020-11-27
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In order to solve the existing technical problem of low reliability in the identification of breast cancer lymph node metastasis, the present invention provides a double-targeting nanoparticle for breast cancer cells and their lymph node metastases, which can efficiently label breast cancer cells, and can effectively The target lymph nodes of the nanoparticles can be differentiated from the inflammatory lymph nodes and normal lymph nodes by the difference of the photoacoustic microscopy signal distribution of the nanoparticles in the lymph nodes of different states, and the accuracy of lymph node metastasis identification of breast cancer can be improved.

Method used

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  • Nanoparticle targeting breast cancer cell and lymph node metastasis focus, preparation method and application
  • Nanoparticle targeting breast cancer cell and lymph node metastasis focus, preparation method and application
  • Nanoparticle targeting breast cancer cell and lymph node metastasis focus, preparation method and application

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Embodiment 1

[0057] The embodiment of the present invention provides a preparation method of nanoparticles for double-targeting breast cancer cells and their lymph node metastases:

[0058] A1, first weigh 14mg HA and dissolve it in 5ml deionized solution, add 6mg carbodiimide (EDAC), and react at 37°C for 2h; then add 0.5mg DMPE phospholipid to the HA solution, and continue to react at 37°C for 24h. After purification, the HA-DMPE polymer is obtained, and finally the HA-DMPE polymer is verified by hydrogen nuclear magnetic resonance spectrum (1H NMR).

[0059] A2, weigh DMPC (3μmol), C.O (0.1μmol), DiR-BOA (0.2μmol), DSPE-PEG200 (0.0114μmol) and HA-DMPE (0.04μmol) respectively in glass test tubes, add 500μl chloroform solution to fully Mix and seal the tube with parafilm.

[0060] A3, vacuum drying

[0061] The mixture in step A2 was passed through a steady stream of nitrogen to dry the chloroform in the test tube, and then the test tube was dried in a vacuum desiccator for 1 h.

[006...

Embodiment 2

[0070] For the toxic effect of the dual-targeted nanoparticles prepared in Example 1 on 4T1 breast cancer cells, see figure 2 . figure 2 It is shown that in the range of 1-40 μM R4F polypeptide concentration of nanoparticles, the interaction between nanoparticles and 4T1 breast cancer cells for 24 hours has basically no great impact on the survival of breast cancer cells. These results indicate that hyaluronic acid-based nanoparticles have good biocompatibility for in vivo applications.

Embodiment 3

[0072] The effect of α-HA-NP prepared in Example 1 targeting lymph nodes is shown in image 3 . After the nanoparticles were subcutaneously injected from mouse footpads, the aggregation effect of nanoparticles in lymph nodes was observed at different time points using a whole-body fluorescence imaging system. The imaging results showed that the dual-targeted nanoparticle α-HA-NP can quickly (less than 10min) accumulate in the lymph nodes of the knee bend, and the fluorescence signal intensity in the lymph nodes is much stronger than that of the single-targeted nanoparticle α-NP in the control group and HA-e. At 6h, the fluorescence signal intensity in the lymph nodes of α-HA-NP group was 3.0 and 2.3 times that of α-NP and HA-e, respectively, and at 12h, it was 3.2 times and 2.5 times, respectively. This result shows that the dual-targeted nanoparticles can target lymph nodes quickly and efficiently, laying the foundation for in vivo labeling of lymph nodes with tumor metasta...

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Abstract

The invention provides a nanoparticle targeting breast cancer cell and lymph node metastasis focus, and belongs to the technical field of bioscience and drug carriers. The nanoparticle comprises phospholipid, cholesterol ester, a near infrared probe, a hyaluronic acid-phospholipid compound and alpha spiral polypeptide. The nanoparticle can effectively mark breast cancer cells and can effectively target lymph nodes, the lymph nodes with tumor metastasis can be distinguished from inflammatory lymph nodes and normal lymph nodes through the distribution difference of photoacoustic microimaging signals of the nanoparticle in the lymph nodes in different states, and the accuracy of breast cancer lymph node metastasis identification is improved. The invention further provides a preparation methodand application of the nanoparticle targeting breast cancer cell and lymph node metastasis focus.

Description

technical field [0001] The invention belongs to the technical field of biological science and drug carrier, and relates to a nanoparticle, a preparation method and an application of double-targeting breast cancer cells and lymph node metastases. Background technique [0002] Breast cancer is the most commonly diagnosed cancer in women and the leading cause of cancer-related mortality in women. Although great advances have been made in the diagnosis and treatment of breast cancer, metastatic breast cancer is often considered to be difficult to cure. Therefore, in order to strike a balance between the benefits of relieving pain and prolonging the patient's life and the harm caused by treatment, a reasonable treatment plan should be based on the different stages of tumor lymph node metastasis. At present, the clinical method for judging whether breast cancer has metastasized is mainly to use radioactive element 99m Tc-labeled nanocolloids or Evans blue dye were injected aroun...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22
CPCA61K49/221A61K49/225
Inventor 张智红戴艳锋骆清铭
Owner HUAZHONG UNIV OF SCI & TECH
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