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Tumor-associated macrophage dual-targeting polypeptide, nanoparticle, preparation and application

A technology of macrophages and nanoparticles, which is applied in the fields of biological science and drug carriers, can solve safety problems and other problems, and achieve the effects of uniform particle size, no aggregation phenomenon, and simple preparation process

Active Publication Date: 2020-09-25
HUAZHONG UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these non-targeted therapies may have safety concerns due to the important role of macrophages in the innate immune response and their systemic distribution properties

Method used

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  • Tumor-associated macrophage dual-targeting polypeptide, nanoparticle, preparation and application
  • Tumor-associated macrophage dual-targeting polypeptide, nanoparticle, preparation and application
  • Tumor-associated macrophage dual-targeting polypeptide, nanoparticle, preparation and application

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Example 1: Tumor-associated macrophage dual-targeting polypeptide

[0033] An embodiment of the present invention provides a dual-targeting polypeptide for tumor-associated macrophages. The dual-targeting polypeptide is composed of an α-helical polypeptide, a linker sequence, and an M2-type macrophage targeting peptide connected in series in the form of covalent bonds. The amino acid sequence of the α-helical polypeptide is FAEKFKEAVKDYFAKFWD, and the amino acid sequence of the α-helical polypeptide is shown in SEQ ID NO.1 in the sequence listing. The amino acid sequence of the linker sequence is GSG. The amino acid sequence of the M2 macrophage targeting peptide is YEQDPWGVKWWY, and the amino acid sequence of the M2 macrophage targeting peptide is shown in SEQ ID NO.2 in the sequence listing.

Embodiment 2

[0034] Example 2: Nanoparticles Targeting Tumor-Associated Macrophages

[0035] An embodiment of the present invention provides a nanoparticle targeting tumor-associated macrophages. The nanoparticle is composed of dual targeting polypeptides, phospholipids, cholesteryl lipids and fat-soluble optical probes. The phospholipid is one or a combination of dimyristoylphosphatidylcholine (DMPC) and distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG2000). The liposoluble optical probe is DiR-BOA.

Embodiment 3

[0036] Example 3: Preparation method of nanoparticles targeting tumor-associated macrophages

[0037] An embodiment of the present invention provides a method for preparing nanoparticles targeting tumor-associated macrophages, comprising the following steps:

[0038] S1, 3 μmol DMPC, 0.0114 μmol DSPE-PEG2000, 0.2 μmol DiR-BOA and 0.1 μmol C.O (cholesteryl ester) were dissolved in 200 μL chloroform. After mixing, the mixture was placed in a nitrogen blower and dried with nitrogen gas. The dried mixture was placed in a vacuum desiccator and dried at room temperature for 1 hour. The dried mixture was dissolved in 2 mL of phosphate buffer, mixed with a vortex shaker, and then ultrasonicated at 48° C. for 1 hour using a sonicator.

[0039] S2. Weigh 0.4 μmol of the dual-targeting polypeptide using an analytical balance, and dissolve it in 3 mL of phosphate buffer. Add the peptide solution dropwise to the hydrated phospholipid and cholesterol mixture and mix well. The peptide, p...

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Abstract

The invention discloses double-target polypeptide of a tumor-associated macrophage, a nano particle, preparation and an application and relates to the technical field of bioscience and drug carriers.The double-target polypeptide is prepared by series connection of alpha helix polypeptide, a catenation sequence and M2 macrophage target peptide in a covalent bond form. The nano particle prepared bythe double-target polypeptide can perform efficient targeted transportation of drugs to the tumor-associated macrophage, so that the tumor-associated macrophage is specifically eliminated and tumor growth is inhibited; a preparation technology of the nano particle targeting to the tumor-associated macrophage is simple; large-scale production is facilitated; most raw materials for preparing the nano particle are used clinically or used in clinical experiments; and a detection result shows that no toxic or side effects are caused on physiologic and biochemical indexes of a mouse.

Description

technical field [0001] The invention relates to the technical fields of biological sciences and drug carriers, in particular to providing a tumor-associated macrophage dual-targeting polypeptide, nanoparticles, preparation and application. Background technique [0002] Tumor-associated macrophages (TAMs) are one of the most abundant leukocytes in tumor tissues, but due to the immunosuppressive effect of the tumor microenvironment, they cannot prevent the development of tumors through normal phagocytosis and antigen presentation reactions. Conversely, TAMs promote tumor growth and progression in a variety of ways. For example, by expressing vascular endothelial growth shadow (VEGF) to promote tumor angiogenesis, thereby providing sufficient nutrients for tumor cells; by expressing inhibitory ligands such as PD-L1, inhibiting the activity of T cells with tumor cell killing ability; by Secrete heterogeneous cytokines such as IL-10, inhibit anti-tumor immune response and so on....

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K9/51A61K47/42A61K47/24A61K47/28A61P35/00
Inventor 骆清铭张智红钱源乔莎
Owner HUAZHONG UNIV OF SCI & TECH
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