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Immune targeting functional liposome as well as preparation method and application thereof

A liposome and functional technology, applied in the field of medicine, can solve problems such as inability to obtain teaching and prompting

Active Publication Date: 2020-04-28
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Then, on the basis of PEGylated phospholipids, modify mannose (Man) or galactose (Gal) to obtain PEGylated phospholipids modified by carbohydrate ligands, and then use PEGylated phospholipids modified by carbohydrate ligands as membrane materials , to construct a blank liposome that does not contain drugs, will it have a good effect or a bad effect on the immunotherapy of tumors? There is no literature report yet, and it is impossible to obtain teaching and hints from existing comparative documents

Method used

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  • Immune targeting functional liposome as well as preparation method and application thereof
  • Immune targeting functional liposome as well as preparation method and application thereof
  • Immune targeting functional liposome as well as preparation method and application thereof

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preparation example

[0048] Mannose-modified phospholipids: Accurately weigh 4-aminophenyl α-D-mannopyranoside, add DMSO solvent, and dissolve with magnetic stirring to make a solution with a concentration of 1 mg / mL; add distearoylphosphatidylethanolamine- PEG 2000 - Aminosuccinimide, the amount added is about 5 times the mass of 4-aminophenyl α-D-mannopyranoside; filled with nitrogen protection, stirred at room temperature and protected from light for 48 hours; dialyzed the reacted solution in DMSO 24 hours to remove unreacted 4-aminophenyl α-D-mannopyranoside, then dialyzed in pure water for 24 hours to remove DMSO, freeze-dried to obtain mannose-modified phospholipids: distearoylphosphatidylethanolamine -PEG 2000 - Mannose;

[0049] Galactose-modified phospholipids: Accurately weigh 4-aminophenyl α-D-galactopyranoside, add DMSO, and dissolve with magnetic stirring to make a solution with a concentration of 1mg / mL; add distearoylphosphatidylethanolamine- PEG 2000 - Aminosuccinimide, the add...

Embodiment 1

[0050] Embodiment 1: the liposome of mannose modification

[0051] Soy Lecithin, Cholesterol, Distearoyl Phosphatidylethanolamine-PEG 2000 and distearoylphosphatidylethanolamine-PEG 2000 - Mannose, add chloroform to dissolve to prepare solutions with concentrations of 20mg / ml, 10mg / ml, 30mg / mL and 30mg / mL, store at -20°C for later use; measure according to the specified mass ratio and the ratio in Table 1 Put various lipid material solutions in a round bottom flask, 40°C, 100rpm under reduced pressure rotary evaporation to remove chloroform, continue rotary evaporation for 1h, add 4mL 55°C preheated PBS (10mM, pH7.4) buffer, 55°C, 100rpm conditions After hydration for 1 h, the mannose-modified liposome suspension was obtained. According to the liposome particle size measurement method in the summary of the invention, the particle size of the prepared liposomes was measured, and the results are shown in Table 1.

[0052] Table 1 The composition of mannose-modified liposome f...

Embodiment 2

[0054] Embodiment 2: the liposome of galactose modification

[0055] Soy Lecithin, Cholesterol, Distearoyl Phosphatidylethanolamine-PEG 2000 and distearoylphosphatidylethanolamine-PEG 2000 -Galactose, add chloroform to dissolve and make solutions with concentrations of 20mg / ml, 10mg / ml, 30mg / mL and 30mg / mL respectively, store at -20°C for later use; Phosphatidylethanolamine-PEG 2000 15% by weight, distearoylphosphatidylethanolamine-PEG 2000 - The weight percentage of galactose is 10%, and the weight percentage of cholesterol is 15%. Measure the above solution in a round bottom flask, remove chloroform by rotary evaporation at 40°C and 100rpm under reduced pressure, continue rotary evaporation for 1h, add 4mL of PBS preheated at 55°C (10 mM, pH 7.4) buffer solution, hydrated for 1 h at 55° C. and 100 rpm to obtain a galactose-modified liposome suspension. According to the liposome particle size measurement method in the summary of the invention, the particle size of the pre...

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to an immune targeting functional liposome as well as a preparation method and application thereof. The functional liposome disclosed by the invention is a blank liposome which does not entrap a drug, a membrane material contains carbohydrate ligand modified PEGylated phospholipid, the average particle size is 50-500nm, and the functional liposome has a targeting function on immunosuppressive cells in a tumor microenvironment and can promote tumor-associated macrophages to differentiate into M1 type macrophages; the polypeptide has a certain capacity of inhibiting tumor growth, can be used as an adjuvant of a tumor immune treatment, and can also be used as an entrapped delivery tool of an immunomodulator oran anti-tumor drug.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an immune-targeting functional liposome, a preparation method and application of the liposome. Background technique [0002] Immunotherapy is a therapeutic measure to fight diseases by regulating the body's own immune system. It has important clinical significance for the treatment of viral infections, autoimmune diseases and cancer, especially the immunotherapy of cancer, which has attracted widespread attention at home and abroad. . Different from chemotherapy, tumor immunotherapy acts on the cells of the immune system, especially the immune cells in the tumor microenvironment, to stimulate and enhance the immune function of the body, and improve the anti-tumor immunity of the tumor microenvironment, so as to control and kill tumor cells antitumor therapy. Its target is immune cells in the tumor microenvironment rather than tumor cells, which has the advantage of...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/60A61K47/54A61K9/127A61P35/00
CPCA61K47/6911A61K47/60A61K47/549A61K9/1277A61P35/00
Inventor 刘玉玲叶军杨艳芳陈晓光孟盈盈高越刘东东冯遇季鸣金晶
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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