Liposome for cancer targeting immunotherapy by natural sugar antibody and preparation method of liposome

A technology of liposomes and phospholipids, which is applied in the direction of antineoplastic drugs, medical preparations of non-active ingredients, and pharmaceutical formulas, and can solve the problems of limiting the application of liposome-encapsulated drugs, large toxic and side effects, and easy leakage.

Inactive Publication Date: 2016-11-23
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, liposome drug loading generally faces a major problem, that is, the encapsulation efficiency is not high and it is easy to leak, and many drugs themselves have high toxicity and side effects, which greatly limit the application of liposome-encapsulated drugs.

Method used

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  • Liposome for cancer targeting immunotherapy by natural sugar antibody and preparation method of liposome
  • Liposome for cancer targeting immunotherapy by natural sugar antibody and preparation method of liposome
  • Liposome for cancer targeting immunotherapy by natural sugar antibody and preparation method of liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Example 1: Rhamnose-coupled polyethylene glycol distearate phosphate ethanolamine

[0098] Accurately weigh 40mg RhaNBuacid, dissolve it in 0.78ml dimethyl sulfoxide (DMSO), and then add 27mg 1,2 distearic acid-3 phosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG2000- NH2) and 0.39ml pyridine (pyridine), then add 81mg dicyclohexylcarbodiimide, react at room temperature for 4 hours. After forming a mist mixture, pyridine was removed by rotary evaporation, and 10 ml of single distilled water was added. The supernatant was collected by centrifugation, and the supernatant was dialyzed twice with 3000 molecular weight dialysis membrane, 50mM 2L saline solution, and 2L deionized water three times, and finally DSPE-PEG2000-Rhamnose was obtained as a white solid by lyophilizing the dialyzate. Synthetic route such as Figure 2-2 shown.

Embodiment 2

[0099] Example 2: Polyethylene glycol distearate phosphoethanolamine coupled with folic acid

[0100] Accurately weigh 79mg of folic acid, dissolve it in 2ml of dimethyl sulfoxide (DMSO), and then add 50mg of 1,2 distearic acid-3 phosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG2000-NH2 ) and 1ml of pyridine (pyridine), followed by adding 96mg of dicyclohexylcarbodiimide and reacting at room temperature for 4 hours. After forming a mist mixture, pyridine was removed by rotary evaporation, and 10 ml of single distilled water was added. The supernatant was collected by centrifugation, and the supernatant was dialyzed twice with 50mM 2L saline solution and three times with 2L deionized water on a dialysis membrane with a molecular weight of 1000. Finally, DSPE-PEG2000-Folate, a yellow solid, was obtained by freeze-drying the dialyzate. Synthetic route such as Figure 2-1 shown.

Embodiment 3

[0101] Example 3: Preparation of immune targeting liposomes

[0102] Preparation of 1,2-dioleoyl-SN-glycerol-3-phosphatidylethanolamine (DOPE), the rhamnose-coupled polyethylene glycol distearate phosphate ethanolamine (DSPE-PEG2000-Rhamnose) obtained in Example 1 , The folic acid-coupled polyethylene glycol distearic acid phosphodylethanolamine (DSPE-PEG2000-Folate) mother solution obtained in Example 2 with three component concentrations of 0.1M, 0.01M and 0.001M were stored at -80°C.

[0103]Take 20μl DOPE, 200μL DSPE-PEG2000-Rhamnose and 2μl DSPE-PEG2000-Folate to make a mixture with a molar ratio of 1000:1000:1 (diluted in 10ml chloroform / methanol (9 / 1)), and place in 250ml clean In a round bottom flask, spin dry on a rotary evaporator at 60 rpm. During rotary evaporation, the round-bottomed flask should be immersed in a 40°C water bath and spin-dried until a uniform lipid film appears. After 15 minutes, the round-bottomed flask left the water surface, and after passing...

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Abstract

The invention provides a novel phospholipid derived compound shaped like phospholipid-PEG (polyethylene glycol)-folic acid or phospholipid-PEG-rhamnose, and further provides a liposome medicine combination containing the phospholipid derived compound and a preparation method of the liposome medicine combination. The novel phospholipid derived compound can be used for cancer targeting immunotherapy, and cancer cells are killed by complement dependent toxicity immuno-targeting. Rhamnose and folic acid modified phospholipid is used as a raw material to prepare liposome, targeting property is fine, the cancer cells are efficiently killed by making full use of human natural immunity, toxic and side effects are small, and the liposome is suitable for clinical application research and industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a liposome for targeted immunotherapy of tumors using natural carbohydrate antibodies, a preparation method and application thereof. Background technique [0002] Rhamnose (Rha) is a monosaccharide that exists in many bacteria but cannot be synthesized in the human body. Numerous studies have shown that rhamnose is immunogenic. Recent studies have found that human serum has a high titer of rhamnose antibodies, and its content is more abundant than α-Gal, and the modified α-Gal has been used to effectively kill tumor cells by using multivalent effects. Moreover, in wild-type mice, the amount of anti-Rha is much larger than that of anti-α-Gal, and there is almost no anti-α-Gal. Knockout of the lactosyltransferase gene is not required by using anti-Rha; in addition, the structure of rhamnose is simpler than that of α-Gal, and it is easier to be modified by chemical methods. Thi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G65/333A61K47/48A61P35/00
CPCC08G65/33396C08G2650/38C08G2650/50
Inventor 易文饶雄剑
Owner ZHEJIANG UNIV
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