Composite liposome, preparation method and application thereof

A compound lipid and plastid technology, applied in the field of medicine and chemical industry, can solve problems such as difficult to effectively control tumor growth and metastasis process, achieve the effects of promoting drug action, inhibiting growth and proliferation, and improving tumor immune microenvironment

Active Publication Date: 2022-02-18
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, photothermal therapy is often accompanied by rapid tumor recurrence, and it is difficult to effectively control the growth and metastasis of tumors.

Method used

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  • Composite liposome, preparation method and application thereof
  • Composite liposome, preparation method and application thereof
  • Composite liposome, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0068] Preparation Example 1: Synthesis of Carboxylated Palmitoyl Lysolecithin 1

[0069]

[0070] P-LysoPC (300mg, 0.6mmol) and succinic anhydride (120mg, 1.2mmol) were dissolved in 5.0mL of dichloromethane, and N,N-dimethylaminopyridine (150mg, 1.2mmol) was added thereto, heated to After reacting at 40° C. for 36 h, the solvent was spun off, and carboxylated palmitoyl lysolecithin 1 (325.7 mg) was separated by a reverse-phase column with a yield of 90.5%.

preparation Embodiment 2

[0071] Preparation Example 2: Synthesis of JQ1-phospholipid conjugate JPC

[0072]

[0073] (S)-(+)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-F][1,2,4] Triazolo[4,3-A][1,4]diazepine-6-yl) tert-butyl acetate (JQ1) (200mg, 0.44mmol) was dissolved in 10.0mL 40% (v / v%) tri In dichloromethane solution of fluoroacetic acid, react at room temperature for 3h. After the reaction was completed, the solvent was spun off, and compound 2 (168 mg) was obtained by column separation with a yield of 95.8%.

[0074] Compound 2 (160 mg, 0.4 mmol) was dissolved in 5.0 mL of dichloromethane, and N,N-dimethylaminopyridine (146.8 mg, 1.2 mmol), 1-(3-dimethylaminopropyl)- 3-Ethylcarbodiimide hydrochloride (230mg, 1.2mmol) and N,N-diisopropylethylamine (198.4μL, 1.2mmol), after activation in ice bath for 2h, add 2-hydroxyethyl di Sulfide (144μL, 1.2mmol), reacted at room temperature for 24h. After the reaction was completed, the solvent was spun off, and compound 3 (165 mg) was obtain...

preparation Embodiment 3

[0076] Preparation Example 3: IR-1061-GPLGLAG-PEG 5k Synthesis

[0077]

[0078] Fmoc-GPLGLAG (250mg, 0.3mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72.4mg, 0.37mmol), 1-hydroxybenzotriazole ( 51.0mg, 0.37mmol) was dissolved in 2.0mL of anhydrous DMF, after activation at room temperature for 1h, mPEG was added 5k -NH 2 (500mg, 0.1mmol), react at room temperature for 24h. After the reaction was completed, the solvent was removed by ethanol dialysis, and the ethanol was spin-dried to obtain compound 4 (430 mg), with a yield of 74.1%.

[0079] Compound 4 (425 mg, 0.073 mmol) was dissolved in 5.0 mL of 20% (v / v%) 4-methylpiperidine in anhydrous DMF, and reacted at room temperature for 24 h. After the reaction was completed, the solvent was removed by ethanol dialysis, and the ethanol was spin-dried to obtain compound 5 (370 mg), with a yield of 90.2%.

[0080] Carboxylated IR-1061 (50mg, 0.062mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydr...

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Abstract

The invention relates to a composite liposome, a preparation method and application thereof. The composite liposome comprises the following components: 1) an immunomodulator-phospholipid conjugate; 2) a PEGylated photosensitive molecule; 3) a tumor treatment drug; and 4) phospholipid, in the composite liposome, the immunomodulator-phospholipid conjugate 1), the PEGylated photosensitive molecule 2) and the phospholipid 4) form a liposome, and the tumor treatment drug 3) is loaded in a physical entrapment form. The compound liposome can selectively target a tumor area, photosensitive molecules in the liposome can be activated to generate heat through local illumination on the tumor area, the permeability of the liposome is changed while tumor cells are killed, and release of loaded drugs in the liposome is promoted.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a composite liposome, its preparation method and its application in tumor immunotherapy. Background technique [0002] Liposome is a closed vesicle with a bilayer structure formed by phospholipids and cholesterol. Its structure is similar to that of the phospholipid bilayer on the cell membrane, which is conducive to its fusion with the cell membrane structure. It is often used as a drug for small molecules and genes. carrier. [0003] Photothermal therapy is to use photosensitive molecules to be activated under local laser irradiation at the tumor site to generate heat, resulting in an increase in local temperature, so as to achieve its destruction of tumor tissue and tumor cell killing. However, photothermal therapy is often accompanied by rapid tumor recurrence, and it is difficult to effectively control the growth and metastasis of tumors. By activa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61K47/54A61K47/60A61K41/00A61K31/704A61K45/06A61P35/00
CPCA61K9/127A61K47/24A61K47/544A61K47/60A61K41/0057A61K41/0028A61K31/704A61K45/06A61P35/00A61K2300/00
Inventor 于海军周丰琦高晶祝奇文
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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