Mitochondrial targeting lipoid carrier Mito-Aliposome, and compound, preparation method and application thereof

A lipid carrier and mito-a technology, applied in other methods of inserting foreign genetic materials, drug combinations, pharmaceutical formulations, etc., can solve the problems of carcinogenic risk and high price of viral vectors, and improve the efficiency and safety of gene transfection sexual effect

Pending Publication Date: 2020-09-01
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some diseases caused by eye gene mutations are mainly caused by mitochondrial DNA mutations. However, adeno-associated virus, the most widely used gene therapy carrier on the market, cannot pass through the mitochondrial double membrane structure. , expensive and other issues

Method used

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  • Mitochondrial targeting lipoid carrier Mito-Aliposome, and compound, preparation method and application thereof
  • Mitochondrial targeting lipoid carrier Mito-Aliposome, and compound, preparation method and application thereof
  • Mitochondrial targeting lipoid carrier Mito-Aliposome, and compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The mitochondrial targeting lipid carrier Mito-Aliposome of this embodiment is composed of auxiliary lipid, cationic lipid and Mito-A in a molar ratio of 9:2:0, 9:2:2 or 9:2:4, wherein In Mito-Aliposome, Mito means mitochondrial targeting group, A means polymer material or cholesterol; Mito-A means polymer material or cholesterol modified with mitochondrial targeting group, and Mito-Aliposome means high Lipid-like carriers of molecular materials or cholesterol.

[0028] The preparation method of the above-mentioned mitochondria-targeted lipid carrier Mito-Aliposome specifically includes the following steps:

[0029] (1) Synthesis of activated polymer material or cholesterol: add 1.2 times molar amount of dicyclohexylcarbodiimide (DCC) and 1.5 times molar amount of N-hydroxybutanediamide to the polymer material or cholesterol at the end of the carboxyl group Imide (NHS), stirred at 25°C-35°C for 12h; then the reaction solution was centrifuged at 10,000rpm for 5min, and ...

Embodiment 2

[0038] Mito-Aliposome / DNA complex particle size of mitochondria-targeting lipid-like carrier composed of helper lipid, cationic lipid and Mito-A in 9:2:0, 9:2:2, 9:2:4 molar ratio Figure; according to the co-incubation of the carrier material synthesized in Example 1 and protist DNA (0.2 μg / μL), 50 μL of complex nanoparticle solution is prepared, and its particle size is measured by dynamic light scattering (DLS), the result is as follows figure 1 shown. The particle size of the complex is a key indicator of the uptake and internalization of the complex by the target site. When the particle size of the complex reaches the micron level, it will hinder the passive targeting of the complex to the target site. In the present invention, the particle size of the complex is about 200nm, and there are It is beneficial for the complex to quickly and passively target the target site to play a role. In this embodiment, the mitochondrial targeting group is selected from triphenylphosphin...

Embodiment 3

[0040] Schematic diagram of the particle size stability of the mitochondria-targeted lipid carrier Mito-Aliposome / DNA complex; according to Example 2, different complex nanoparticle solutions were obtained and diluted with physiological saline, figure 2 Figures (a), (b) and (c) are nanoparticles mixed with helper lipids, cationic lipids and Mito-A at molar ratios of 9:2:0, 9:2:2, and 9:2:4, respectively. The stability of the solution. The particle size stability of the complex is the premise to ensure that the complex can be stored stably and function in vivo, and the complexes in the present invention can maintain good particle size stability within 24 hours. In this embodiment, the mitochondrial targeting group is selected from triphenylphosphine. The polymer material or cholesterol is selected from polylactic acid-glycolic acid copolymer-polyethylene glycol (PLGA-PEG, molecular weight 11K). The cationic lipid is selected from O-[(N,N-dimethylaminoethyl)-carbamoyl]cholest...

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Abstract

The invention discloses a mitochondrial targeting lipoid carrier Mito-A1iposome, and a compound, a preparation method and application thereof. The mitochondrial targeting lipoid carrier Mito-Aliposomecomprises an auxiliary lipid, a cationic lipid and Mito-A, wherein Mito in the Mito-Aliposome represents a mitochondrial targeting group, and A represents a high polymer material or cholesterol; theMito-A represents a mitochondrial targeting group modified high polymer material or cholesterol; and the Mito-Aliposome represents a lipoid carrier with the mitochondrial targeting group modified highpolymer material or cholesterol. The compound comprises the mitochondrial targeting lipoid carrier Mito-Aliposome and a therapeutic gene, and the compound is formed through electrostatic interactionafter co-incubation of the mitochondrial targeting lipoid carrier Mito-Aliposome and the therapeutic gene. The carrier can efficiently deliver the therapeutic gene into mitochondrial matrixes, and theeffect of radically treating eye mitochondrial gene mutation diseases is achieved.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to mitochondria-targeted lipid carrier Mito-Aliposome, its complex, preparation method and application. Background technique [0002] Gene therapy is a method of molecular biology to introduce normal or therapeutic genes into target cells to correct or compensate diseases caused by gene defects and abnormalities, so as to achieve the effect of treating or improving certain diseases . For some ocular mitochondrial gene mutation diseases, there is currently no effective treatment strategy. Currently, small molecule drugs are mainly used in clinical practice to alleviate the symptoms of the disease, which cannot fundamentally treat the disease. Gene therapy can intervene in the occurrence and development of diseases by manipulating genetic material, so as to achieve the goal of radical cure. Therefore, it is of great significance to develop mitochondrial-targeted gene ther...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61P21/00A61P27/02C12N15/88
CPCA61K48/0025A61K48/005A61P27/02A61P21/00C12N15/88
Inventor 姜虎林王译胡力凡邢磊戴昱孙建国
Owner CHINA PHARM UNIV
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