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Construction of high-penetrability tumor target lipid insert and effect thereof in promoting cell and cell membrane preparation to aggregate toward tumor

A tumor-targeting, high-penetration technology, applied in the direction of anti-tumor drugs, allergic diseases, non-active ingredients of polymer compounds, etc., can solve the problems of slow progress in the treatment of solid tumors, achieve good tumor targeting, The effect of good reproducibility and simple preparation process

Inactive Publication Date: 2017-07-07
NANJING DRUM TOWER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the field of immune cell therapy, which is attracting more and more attention, although there are tumor targeting similar to chimeric antigen receptor T cell therapy, the progress in the treatment of solid tumors is slow

Method used

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  • Construction of high-penetrability tumor target lipid insert and effect thereof in promoting cell and cell membrane preparation to aggregate toward tumor
  • Construction of high-penetrability tumor target lipid insert and effect thereof in promoting cell and cell membrane preparation to aggregate toward tumor
  • Construction of high-penetrability tumor target lipid insert and effect thereof in promoting cell and cell membrane preparation to aggregate toward tumor

Examples

Experimental program
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Effect test

Embodiment 1

[0062] Take iRGD-PEG-DSPE modified T cells as an example to modify cells with lipid plug-in containing penetrating peptide iRGD components.

[0063] The technical idea of ​​the present invention is: inserting lipid chain-modified iRGD onto the surface of immune cells activated in various ways, promoting the targeted aggregation of cells in tumors, and improving the curative effect of immune cell therapy. The present invention takes cytotoxic T lymphocyte (CTL) cells stimulated by Epstein-Barr virus antigen peptides as an example, but is not limited to such immune cells.

[0064] Figure 1-Figure 9 Taking iRGD-PEG-DSPE modified T cells as an example to introduce the lipid plug-in modified cells containing penetrating peptide iRGD components. However, the present invention is not limited by the type and molecular phenotype of the cells.

[0065] The preparation of the penetrating peptide plug-in with active tumor targeting ability and its functional verification are as follows...

Embodiment 2

[0098] Taking anti-EGFR-iRGD-PEG-DSPE modified erythrocyte membrane drug-loaded particles as an example, the lipid plug-in modified cell membrane preparation containing penetrating peptide iRGD component was carried out.

[0099] The technical idea of ​​the present invention is: obtain anti-EGFR-iRGD gene coding fragment through gene recombination technology, transfer it into prokaryotic expression vector, activate expression, extract, purify and identify after expression. Subsequently, the prepared nanobody fusion protein is lipid-modified and inserted into various cell membrane carriers to achieve tumor targeting of the carrier.

[0100] Figure 10-Figure 18 Taking anti-EGFR-iRGD-PEG-DSPE modified erythrocyte membrane drug-loaded particles as an example to introduce the lipid plug-in modified cell membrane preparation containing penetrating peptide iRGD component. But the present invention is not limited to the type of anti-EGFR-iRGD fusion protein, cell membrane and entrap...

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Abstract

The invention relates to a high-penetrability tumor target lipid insert and a preparation method thereof. The insert is prepared from a high-penetrability peptide iRGD containing ingredient and DSPE-PEG-MAL, and can be inserted onto a plurality of drug-loaded systems and cells to realize active tumor target. According to the preparation method, the substance of the high-penetrability peptide iRGD containing ingredient serving as a molecule for realizing tumor active target and high penetrability is used for modifying a segment of lipid molecules to form a multi-functional tumor target insert capable of definitely reinforcing tumor target. Repeated experiments after successful construction verify that the tumor target lipid insert has definite tumor targeting and can be used for actually reinforcing tumor local aggregation of cell and cell membrane preparations and improving the anti-tumor treatment effect.

Description

technical field [0001] The invention belongs to the technical field of biology and new medicine, and in particular relates to the preparation of a high-penetration tumor-targeting biofilm drug-carrying system, active-targeting high-penetration cells and their application in antitumor. Background technique [0002] Before the present invention, various anti-tumor drugs including traditional chemotherapeutic drugs and anti-tumor drug nano-preparations mostly lack active tumor targeting, and the therapeutic effect is unsatisfactory. The distribution of these drugs after entering the human body is mostly non-tissue-specific, and due to the complex tumor microenvironment, the drugs cannot penetrate deep into the tumor lesion, affecting their anti-tumor effect. So far, through the continuous efforts of researchers, different types of active tumor-targeting nanocarriers have been developed, but these technologies are mostly limited to experimental research. In the past ten years, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61P35/00A61P37/02
CPCA61K47/42
Inventor 刘宝瑞沙慧子丁乃清
Owner NANJING DRUM TOWER HOSPITAL
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