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Transmembrane anti-inflammatory peptide modified tumor-targeting multi-drug co-loaded liposome and preparation method thereof

A tumor-targeting and anti-tumor drug technology, which is applied to multi-drug co-carrier liposomes and their preparation, and the application fields of anti-inflammatory synergistic anti-tumor targeted therapy to achieve the effect of improving curative effect

Pending Publication Date: 2019-12-10
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there have been many reports on multi-drug combined DDS, and some results have been achieved. However, these multi-drug combined DDS designed for tumor cells or for the tumor microenvironment have limitations, and most of them lack the ability to control tumor cells and tumor microenvironment. In the overall consideration of the overall complex system of the environment, the effect of blocking certain pathways or killing certain cells is local and temporary. For a powerful and meticulous tissue like a tumor, other pathways will be activated and activated to promote its more malignant development

Method used

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  • Transmembrane anti-inflammatory peptide modified tumor-targeting multi-drug co-loaded liposome and preparation method thereof
  • Transmembrane anti-inflammatory peptide modified tumor-targeting multi-drug co-loaded liposome and preparation method thereof
  • Transmembrane anti-inflammatory peptide modified tumor-targeting multi-drug co-loaded liposome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] 1) Synthesis of CN-PEG-DSPE:

[0051] 2ml of DSPE-PEG containing 1μmol 2000 -MAL aqueous solution was added dropwise to 1 ml of CN (YGRKKRRQRRR-G-TTLDWSWLQMEC) aqueous solution containing 2 μmol, stirred at room temperature for 12 hours, and the reaction solution was freeze-dried to obtain a white loose solid, yielding CN-PEG-DSPE;

[0052] 2) Preparation of HA / CN-(CXB&DOX)LP

[0053] Weigh 5mg of DOTAP, 24mg of SPC, 3.6mg of cholesterol, 5.4mg of CN-PEG-DSPE and 3mg of CXB, dissolve in 1.5ml of chloroform-methanol (4:1, v / v) mixed solution, 40°C The organic solvent was removed by rotary evaporation to form a uniform lipid film. Add 3ml of PBS buffer solution (containing 0.3% Tween 80) at pH 5.7, rotate and hydrate at 40°C for half an hour, collect the suspension, and ultrasonically pulverize it for 3 minutes to obtain a liposome suspension with uniform particle size, centrifuge at 10,000rpm for 1h Collect the supernatant to obtain CN-(CXB)LP;

[0054] CN-(CXB)LP wa...

Embodiment 2

[0056] In the same preparation method as in Example 1, the amino acid sequence of CN in the prescription was changed to YGRRARRRARR-G-TALDWSWLQTEC with the same molar number, and the dosage of other components in the prescription was fixed to prepare another CN peptide-modified liposome.

Embodiment 3

[0058] With the same preparation method as in Example 1, the CXB in the prescription was changed to the same dose of CUR, and the dosage of other components in the prescription was fixed to prepare HA / CN-(CUR&DOX)LP.

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Abstract

The invention belongs to the technical fields of biomedicine technology and nanomedicine, and discloses a tumor-targeted liposome drug delivery system with three drugs co-loaded. A multifunctional drug delivery system which actively targets tumors is prepared by the steps that cationic liposome is used as a basic carrier, anti-inflammatory drugs and anti-tumor drugs are loaded in the liposome at the same time, a transmembrane anti-inflammatory peptide is covalently linked to the surface of the liposome, and then the outer layer of the cationic liposome is coated with hyaluronic acid. The liposome simultaneously has the functions such as targeted accumulation and deep penetration of tumor tissue, specific recognition of tumor cells and efficient uptake of the tumor cells and interstitial cells thereof. The multifunctional liposome carrier can co-deliver the transmembrane anti-inflammatory peptide, the anti-inflammatory drugs and the anti-tumor drugs to the tumors, fully exerts the synergistic therapeutic effect of the combined drugs, blocks the key signaling pathways of excessive activation of the tumor cells and the interstitial cells, can reduce the level of inflammation and immunosuppression in the tumors, destroy tumor microenvironment, cuts off tumor cell migration pathways, and finally clears the tumor cells and tumor stem cells.

Description

technical field [0001] The invention belongs to the fields of biomedicine technology and nanomedicine technology, and relates to a membrane-penetrating anti-inflammatory peptide-modified multi-drug co-carrying liposome, a preparation method thereof and an application in anti-inflammatory synergistic anti-tumor targeted therapy. Background technique [0002] Studies have shown that chronic "uncontrollable inflammation" plays an important role in the occurrence and development of malignant tumors; chronic inflammation can promote the occurrence of different types of cancer, not only patients with specific inflammatory diseases are prone to cancer, but also tumors that have nothing to do with inflammation (such as Inflammatory microenvironment also exists in breast cancer). In the process of chronic inflammation-mediated tumorigenesis, inflammatory factors can weave tumor cells and their microenvironment into an inflammatory network, and NF-κB and STAT3 are the two key transcri...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/64A61K47/61A61K31/704A61P35/00A61P29/00A61K31/635A61K31/12
CPCA61K47/6911A61K47/64A61K31/635A61K31/12A61K31/704A61K47/61A61P29/00A61P35/00A61K2300/00
Inventor 姜嫣嫣孙雨晴李绪乾刘敬璇
Owner FUDAN UNIV
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