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Preparation and application of targeted mitochondrion nano particles on the basis of composite porcelain body

A technology targeting nanoparticles and porposomes, which can be used in liposome delivery, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc., which can solve the problems of unstable liposomes and limited applications.

Inactive Publication Date: 2016-07-06
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the morphological instability of liposome itself limits its application.

Method used

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  • Preparation and application of targeted mitochondrion nano particles on the basis of composite porcelain body
  • Preparation and application of targeted mitochondrion nano particles on the basis of composite porcelain body
  • Preparation and application of targeted mitochondrion nano particles on the basis of composite porcelain body

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Experimental program
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Effect test

Embodiment 1

[0032] Preparation of targeted nanocomposite drug-loaded porcelain bodies:

[0033] 1) Synthesis of porcelain body monomer: The hydrophobic chain of the porcelain body monomer is condensed by dihexadecane amine and hexadecane bromide. By introducing succinic anhydride as Linker, a carboxyl group is introduced at the hydrophobic end, and the carboxyl end is combined with aminopropanol Hydrophilic silicon ends were introduced by amidation reaction with triethoxysilane.

[0034] 2) Monomers self-assemble to form porcelain bodies: Take 0.1 mmol of amphiphilic porcelain body monomers, place them in pH 3.0 HCl acidic aqueous solution, vortex and shake at room temperature for 15 minutes, ultrasonically probe for 15 minutes, and let the ethoxy silicon A Si-O-Si network structure is formed by condensation. The self-assembly is achieved by vortex sonication, the vortex makes the multilayer capsule structure formed, and the ultrasound disperses the multilayer capsule structure into a bi...

Embodiment 2

[0037] Characterization of targeted nanocomposite drug-loaded porcelain plastids:

[0038](1) Nanoparticle size and particle size distribution: The prepared nanoparticles are placed in an acidic aqueous solution, centrifuged to precipitate large particles, and the dynamic light scattering (DLS) method is used to detect the particle size, particle size distribution and nanoparticle size of the nanoparticles. polydispersity coefficient. DLS detects that the particle size distribution of nanoparticles is around 213.6nm, and the polydispersity index (PDI) is 0.106 ( figure 1 ).

[0039] (2) Nanoparticle TEM: ultrasonically disperse the nanoparticles evenly in a water bath, drop one drop onto the ordinary carbon film with a transmission electron microscope of 200-230 mesh, observe with a transmission microscope after 2-3 minutes. The TEM image shows that the nanoparticles are uniformly distributed, and the particle size distribution is 38.15±7.89nm ( figure 2 ).

[0040] (3) T...

Embodiment 3

[0043] Investigation of the targeting effect of nanoparticles:

[0044] The mitochondrial targeting small molecule TPP is used as the model targeting molecule, and the targeting is modified on the surface of nanoparticles loaded with the hydrophilic fluorescent drug doxorubicin hydrochloride. Non-target-modified nanoparticles and target-modified nanoparticles were dialyzed in PBS for 72 hours to remove impurity small molecules. After the purified nanoparticles were concentrated, they were co-incubated with HeLa cells for 4 hours. After incubation, the mitochondrial fluorescent probe MitotrackerDeepRed was added and co-incubated with Hela cells for 30 min. The cells were washed three times with PBS to avoid the interference of nanoparticles and mitochondrial fluorescent probes in the medium that did not enter the cells. The small dishes were observed under a confocal laser microscope. Judging from the co-localization effect of nanoparticles and MitotrackerDeepRed in mitochon...

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Abstract

The invention discloses the preparation and application of a target mitochondrial nanoparticle based on a composite porcelain plastid. It uses nano-porcelain as a drug carrier, and modifies targeted small molecules on its surface after embedding the drug by self-assembly method. The nanoporcelain has stable structure, time stability and structural stability, and the drug embedded in it can be released slowly. After surface modification of targeted small molecules, nanoparticles can achieve targeted slow release. In cells, nanoparticles achieve a good effect of targeting organelles. It has important application significance for chronic diseases such as Kinson's disease and cancer that require long-term treatment.

Description

technical field [0001] The invention relates to the preparation and application of targeting mitochondrial nanoparticles, in particular to the preparation and application of nano drug-loaded composite liposomes modified with targeting factors. Background technique [0002] Mitochondrial dysfunction is the cause of many human diseases, such as Alzheimer's disease, Parkinson's disease, obesity, diabetes, etc. (Document 1: DuchenMR. Galluzzi L., Kroemer G., Nat Rev Drug Discov (2010) 9: 447-464; Document 3: Galluzzi L, et al., Mol Aspects Med (2010) 31: 1-20). Many drugs have been developed now, which can treat mitochondrial diseases well under in vitro conditions, such as antioxidants for the treatment of Alzheimer's disease (document 4: JayaR.P.Prasanthi, Matthew Schrag, et al., Journal of Alzheimer's (2012) 30:167-182), chemotherapy drugs for cancer treatment (Document 5: NeuzilJ, et al., JBioenerg Biomembr (2007) 39:65-72), anti-oxidative phosphorylation decoupling agents ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61K31/704A61P35/00
Inventor 谭明乾王艳妨马小军
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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