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Multi-purpose cerium dioxide nanometer drug-loading system realizing targeted stimulation responsiveness

A stimuli-responsive, ceria-based technology, applied in the field of nano-biomedical materials, can solve problems affecting the toxicity of cancer cells, the limitation of synergy of cancer cells, etc., achieve good application and development prospects, and improve the effect of lethality

Active Publication Date: 2017-07-25
NORTHWEST A & F UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the process of controlled release of anticancer drugs, cyclodextrin is still wrapped on ceria nanoparticles. The toxicity of cancer cells, so that the synergistic effect of ceria and drugs on cancer cells is greatly limited

Method used

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  • Multi-purpose cerium dioxide nanometer drug-loading system realizing targeted stimulation responsiveness
  • Multi-purpose cerium dioxide nanometer drug-loading system realizing targeted stimulation responsiveness
  • Multi-purpose cerium dioxide nanometer drug-loading system realizing targeted stimulation responsiveness

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044]

[0045] Synthesis of galactose derivative 1: under nitrogen protection, 2g (5.12mmol) peracetylated galactose was dissolved in 15mL of dichloromethane; at the same time, 12mL of hydrobromic acid (concentration of hydrobromic acid 33%, dissolved In acetic acid, HBr) was obtained and reacted at room temperature for 2h. After the reaction of the raw materials was detected by TLC, 20 mL of ice water and 20 mL of dichloromethane were added to separate the layers. The aqueous layer was extracted with 3*20 mL of dichloromethane, and the organic layer was washed with 100 mL of saturated sodium bicarbonate until neutral. Finally, the organic layer was washed once with 50 mL of saturated sodium chloride, dried with anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain galactose derivative 1.

[0046] Since the galactose derivative 1 was very unstable, the next reaction was carried out directly. 2g galactose derivative 1, 1.6g (1eq.) tetrabutyl ...

Embodiment 2

[0048]

[0049] The synthesis of compound 4: with 11g hydroquinone 3 (100mmol), potassium carbonate (K 2 CO 3 ) 27.6g (200mmol), 47.5g (200mmol) of propyne bromide were dissolved in 180mL of acetonitrile, and heated to reflux for 24h under nitrogen protection. After the TCL detection reaction is completed, filter and spin dry in vacuum, dissolve with dichloromethane and wash with distilled water three times. After liquid separation, the organic layer was dried with anhydrous sodium sulfate and separated by column chromatography to obtain compound 4 (89%).

Embodiment 3

[0051]

[0052] Synthesis of Compound 5: Dissolve 2.72g of Compound 4 (20mmol) in 60mL of dichloroethane, add 1.398g of paraformaldehyde (40mmol) under nitrogen atmosphere, and stir for 1 hour at room temperature with 4ml of boron trifluoride diethyl ether. After the reaction was detected by TLC, ice water was added to quench, the organic layer was washed three times with water and saturated sodium chloride three times, and finally dried with anhydrous sodium sulfate, and separated by column chromatography to obtain compound 5 (75%).

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Abstract

The invention relates to a multi-purpose cerium dioxide nanometer drug-loading system realizing the targeted stimulation responsiveness. According to the multi-purpose cerium dioxide nanometer drug-loading system, cerium dioxide with cytotoxicity is taken as a drug-loading main body, sugar is taken as a targeting group, the pillar [5] arene realizing sugar functionalization is taken as a host molecule, pyridinium salt modified on the surface of the cerium dioxide drug-loading main body and containing disulfide bonds is taken as a guest molecule, through the host-guest interaction, the pillar [5] arene realizing sugar functionalization is bonded to the surface of cerium dioxide adsorbing anti-cancer drug, and thus the anti-cancer drug is encapsulated to the surface of the drug-loading main body. Since the pillar arene containing galactosyls is connected to the surface, the biocompatibility of the system can be obviously improved; meanwhile, the galactosyls can act with specific galactose binding protein excessively expressed on the surfaces of cancer cells, so that the targeted selective entering into the cancel cells is realized, further, GSH with high concentration in the cancer cells is utilized for promoting disulfide bonds in the system to rapidly fracture, then the anti-cancer drug is released, the cerium dioxide nanometer particles with cytotoxicity are exposed out, and the synergy in resisting caner of the cerium dioxide nanometer particles and drug is realized.

Description

technical field [0001] The invention belongs to the field of nano biomedical materials, and in particular relates to a targeted stimulus-responsive multifunctional ceria nanometer drug loading system, which is applied to the transport of anticancer drugs. Background technique [0002] In the field of drug application, many active drug molecules have encountered many problems before and during clinical application. For example, the physical and chemical properties of drugs (poor water solubility, poor permeability, etc.) limit their clinical application; Normal tissue is highly toxic. Therefore, the development of suitable drug carriers has become the most economical and effective means to solve this problem. Among many new drug carriers, the porous structure of porous nanomaterials makes them ideal drug carriers. [0003] In drug delivery systems, in addition to the role of porous nanomaterials as drug carriers, many nanomaterials themselves have potential pharmacological ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/02A61K47/26A61K47/22A61K47/06A61K45/00A61P35/00
CPCA61K9/5115A61K9/5123A61K45/00
Inventor 裴志超吴晓文裴玉新张营卢玉超
Owner NORTHWEST A & F UNIV
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