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A kind of fluorinated fluorescent phospholipid and its synthesis method and application

A technology of fluorescent phospholipid and synthesis method, which is applied in chemical instruments and methods, compounds of Group 5/15 elements of the periodic table, organic chemistry, etc., can solve the problem that contrast agents cannot be effectively detected by MRI, affect the loading of other functional molecules, fluorine-based The problems of low encapsulation efficiency of compounds can increase the stability and application value, increase the water solubility and biocompatibility, and improve the poor water solubility.

Active Publication Date: 2020-01-24
WUHAN INST OF PHYSICS & MATHEMATICS CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The stability is relatively poor, and the packaged contrast agent is easy to leak; the encapsulation efficiency of the poorly water-soluble fluorine compound is low, so that the contrast agent cannot be effectively and accurately used for MRI detection of the target site (Adv.Drug Deliver.Rev., 2013 ,65,36-48)
In addition, after a large amount of contrast agent is encapsulated inside the liposome, it will affect the loading of other functional molecules (drugs)

Method used

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  • A kind of fluorinated fluorescent phospholipid and its synthesis method and application
  • A kind of fluorinated fluorescent phospholipid and its synthesis method and application
  • A kind of fluorinated fluorescent phospholipid and its synthesis method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] A synthetic method for fluorinated fluorescent phospholipids, comprising the steps of:

[0053] (1) Dissolve 1g (3.62mM) of 4-bromo-1,8-naphthalene anhydride in 30ml of ethanol, add 323mg (3.62mM) of alanine, then reflux at 80°C for 8h, and monitor the reaction progress by thin-layer chromatography. After the reaction solution changed from gray to brown, the reaction was stopped, and the reaction product was subjected to vacuum filtration, and the solid obtained by suction filtration was redissolved in 30ml of ethanol, and then subjected to suction filtration, and the obtained solid was vacuum-dried to obtain a brown solid compound 1 with a yield of about 90% %, no need for further purification, directly used in the next step; wherein, the structural formula of compound 1 is:

[0054]

[0055] As can be seen from the above, the reaction formula of this step is as follows:

[0056]

[0057] (2) Dissolve 1g (2.88mM) of compound 1 prepared in step (1) in 20ml of DMF...

Embodiment 2

[0071] The specific process of labeling fluorinated thermosensitive liposomes with fluorinated fluorescent phospholipids described in Example 1 is:

[0072] Dissolve 14.68mg DPPC, 1.57mg MPPC, 2.49mg PEG2000-DSPE, 2.19mg F-PC (90:10:4:10, molar ratio) in 5ml chloroform, remove the organic solvent by rotary evaporation, and make the phospholipids form a film. Vacuum dry overnight. Then add 4ml of 3.75mg DOX (1:0.2, mass ratio of phospholipid to drug) aqueous solution, ultrasonicate at 60°C for 10min, and extrude 10 times with a 200nm filter membrane. The prepared liposome was dialyzed, the molecular weight cut-off of the dialysis bag was 10KD, the solvent was deionized water, and the dialyzed for 12h. The liquid in the dialysis bag is freeze-dried to obtain the freeze-dried powder of the liposome.

Embodiment 3

[0074] Example 2 Application of fluorinated thermosensitive liposomes labeled with fluorinated fluorescent phospholipids in nuclear magnetic imaging:

[0075] Taking the fluorinated fluorescent phospholipid-labeled fluorinated thermosensitive liposome synthesized in Example 2 as an example to conduct a temperature responsive experiment in an aqueous medium, and to illustrate its use for fluorine imaging under heating conditions.

[0076] Test method: Liposomes are made into different concentrations of aqueous solutions (10, 20, 40, 60, 80 mg / ml, 10% D 2 O+90%H 2 O), 19F NMR at different temperatures (25, 37, 38, 39, 40, 41, 42° C.) were tested with a 500 MHz nuclear magnetic spectrometer. Another 40mg / ml liposome sample was prepared, and its 19F NMR was tested at 42°C at different times (1, 3, 5, 10, 20, 30min) with a 500MHz nuclear magnetic spectrometer, to verify that it was slightly higher than body temperature. temperature responsiveness. Another 20mg / ml liposome sample...

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Abstract

The invention discloses a fluorinated fluorescence phospholipid, synthesis method, and applications of same, and belongs to the technical field of preparation and application of novel phospholipids. The method includes steps of: performing a reaction to 4-bromo-1,8-anhydride naphthalene with alanine to obtain a compound (1); performing a reaction to the compound (1) with sodium azide to obtain a compound (2); performing a click chemical reaction to the compound (2) with trifluorophenylacetylene to prepare a compound (3); performing a reaction to the compound (3) with stearoyl lysoph-osphatidylcholine to obtain a target product (4). The fluorinated fluorescence phospholipid can be used for labeling a temperature-sensitive lipidosome, which can achieve on / off conversion of fluorine nuclear magnetism signals and achieve multi-time reversible conversion under temperature control, and also allows fluorescence imaging and nuclear magnetism imaging at the same time. The fluorinated fluorescence phospholipid effectively improves problems of poor water solubility and biocompatibility of a fluorine-type contrast medium, can increase carrier utilization rate by means of the multi-time reversible nuclear magnetism signal control, can increase detection accuracy and effectiveness of a target by means of the nano system and temperature control, and has great application value.

Description

technical field [0001] The invention belongs to the technical field of preparation of fluorescent / NMR multifunctional probe molecules and biological detection, and specifically relates to a fluorinated fluorescent phospholipid and its synthesis method and application. The fluorinated phospholipid can label a carrier with an amphiphilic structure, making it 19F MRI and fluorescence imaging can be performed simultaneously. It not only solves the problem of poor water solubility of many fluorine-based molecular probes, but also increases biocompatibility, and realizes multiple functions at the same time, and has a prospect of wide application. Background technique [0002] 19F (fluorine) is one of the commonly used non-proton nuclei for magnetic resonance imaging. Its natural abundance is 100%, its spin is 1 / 2, and its detection sensitivity is high; its content in the human body is very small, and there is almost no background signal. Effective information can be obtained afte...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F9/6558A61K49/00A61K49/10
CPCA61K49/0002A61K49/0021A61K49/10C07F9/65583
Inventor 周欣任莉莉陈世桢孙献平刘买利
Owner WUHAN INST OF PHYSICS & MATHEMATICS CHINESE ACADEMY OF SCI
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