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Surface modification method for cerium nano-particles

A nanoparticle and surface modification technology, which is applied in the field of biomedical chemistry, can solve the problems of difficult functional molecule connection, toxic and side effects, and uncertain effectiveness, so as to achieve the reduction of non-specific interaction, the reduction of macrophage phagocytosis, and significant technical progressive effect

Inactive Publication Date: 2014-02-05
ARMY MEDICAL UNIV
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AI Technical Summary

Problems solved by technology

Modifying PEG on the surface of nanoparticles is one of the effective means to improve the stability of nanoparticles and reduce the capture of nanoparticles by the mononuclear phagocytosis system (Angew.Chem.Int.Ed.2011, 50, 1980-1994; Nanomedicine2011, 6, 715-728), Therefore, previous studies have tried to modify PEG on the surface of CNPs, such as A.S.Karakoti (J.Am.Chem.Soc.2009, 131, 14144-14145), etc. to synthesize CNPs directly in PEG solution, but this method will have large-sized nanoparticles Moreover, there are no active functional groups on the surface of nanoparticles that can be further reacted, making it difficult to further connect with other functional molecules. In addition, the report did not study the stability of CNPs under physiological conditions.
In addition, L. Qi (ACS Nano2008, 2, 879-888) and A. Cimini (Acta Biomater. 2012, 8, 2056-2067) also tried to use small molecules as PEG anchor groups to carry out CNPs PEGylation studies, these studies have not systematically studied the stability of nanoparticles after PEGylation, the capture of mononuclear phagocytosis system, etc., so its effectiveness cannot be determined; recently C.K.Kim et al. (Angew.Chem.Int.Ed. 2012,51,11039-11043) modified phospholipids to PEG, and PEGylated nanoparticles through the hydrophobic interaction between phospholipids and the original protective molecule oleylamine on the surface of CNPs. Although this study obtained relatively stable PEGylation CNPs, but this method does not remove the original oleylamine on the surface of nanoparticles, oleylamine is a toxic substance, which can produce unpredictable toxic side effects after entering the body
[0004] Bisphosphoric acid (referred to as "BP") compounds have high stability and are easy to form bidentate or even multidentate ligands with calcium, copper, iron, uranium, magnesium and other metals or metal oxides (J.Control.Release .2013,167,175–188), there have been reports in the literature that BP compounds are used for iron (Chem.Commun.2008,2553-2555; ACS Nano2013,7,500–512), calcium phosphate (J.Control.Release.2011,150, 87–93) and other nanoparticle surface modification, but there is no literature report on the use of BP compounds for CNPs surface modification, let alone the use of BP compounds as anchor molecules for PEGylation of CNPs.

Method used

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  • Surface modification method for cerium nano-particles
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  • Surface modification method for cerium nano-particles

Examples

Experimental program
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Effect test

Embodiment 1

[0036] Embodiment 1MCNPs-BP-PEG 600 Synthesis of (wherein BP is alendronate sodium, PEG 600 PEG dicarboxylic acid with a molecular weight of 600)

[0037] (1) Synthesis of MCNPs: Dissolve 0.75g AOT in 50mL toluene and add 2.5mL cerium nitrate with a concentration of 0.1mol / L. After stirring for 45min, add hydrogen peroxide (30%) dropwise at a speed of 5r / min with a peristaltic pump. The above solution was reacted at room temperature for 45 minutes and left to stand overnight to obtain MCNPs dispersed in toluene with a diameter of 3-5 nm;

[0038] (2) BP-PEG 600 Synthesis: 147mg PEG dicarboxylic acid, 30mg EDC·HCl and 15mg NHS were dissolved in 2mL of dichloromethane, reacted at room temperature for 6h and then the dichloromethane was removed by rotary evaporation; 20mg of alendronate sodium trihydrate and 50mg of carbonic acid Sodium was dissolved in 4 mL of deionized water and added to the above product, and reacted at room temperature for 12 hours to obtain the nanopartic...

Embodiment 2

[0049] Embodiment 2TCNPs-BP-PEG 600 Preparation (wherein BP is alendronate sodium, PEG 600 PEG dicarboxylic acid with a molecular weight of 600)

[0050] (1) Dissolve 0.434g of cerium nitrate in 0.802g of oleylamine (70%) and 4.0g of 1-octadecene (90%), stir and mix well and raise the temperature to 80°C within 3min, and react for 30min under the protection of argon. Under the condition of condensing reflux and argon gas, heat up to 260°C within 8 minutes and react for 2 hours. After cooling to room temperature, add acetone-absolute ethanol mixed solution (80mL), centrifuge the precipitate, wash it with the same solution several times, and finally disperse it TCNPs with a diameter of 3-5nm were obtained in alkane, which were precipitated with acetone and dispersed in tetrahydrofuran for ligand exchange reaction;

[0051] (2) BP-PEG 600 Synthesis: 147mg PEG dicarboxylic acid, 30mg EDC·HCl and 15mg NHS were dissolved in 2mL of dichloromethane, reacted at room temperature for ...

Embodiment 3

[0055] Embodiment 3MCNPs-BP-PEG 2000 Synthesis of (wherein BP is alendronate sodium, PEG 2000 PEG dicarboxylic acid with a molecular weight of 2000)

[0056] (1) Synthesis of MCNPs: Dissolve 0.75g AOT in 50mL toluene and add 2.5mL cerium nitrate with a concentration of 0.1mol / L. After stirring for 45min, add hydrogen peroxide (30%) dropwise at a speed of 5r / min with a peristaltic pump. The above solution was reacted at room temperature for 45 minutes and left to stand overnight to obtain MCNPs dispersed in toluene with a diameter of 3-5 nm;

[0057] (2) BP-PEG 2000 Synthesis: 392mg PEG dicarboxylic acid, 40mg EDC·HCl and 20mg NHS were dissolved in 4mL of dichloromethane, reacted at room temperature for 8h and then the dichloromethane was removed by rotary evaporation; 40mg of alendronate sodium trihydrate and 50mg of carbonic acid Sodium was dissolved in 4 mL of deionized water and added to the above product, and reacted at room temperature for 24 hours to obtain the nanopa...

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Abstract

The invention relates to a surface modification method for CNPs (cerium nano-particles), which comprises the following steps: synthesizing CNPs coated with bis(2-ethylhexyl) sulfosuccinic acid and CNPs coated with oleylamine by adopting a micro-emulsion method and a high temperature thermal decomposition method; then covalently binding a diphosphonate compound and polyethylene glycol through a chemical reaction to obtain a modified ligand; finally, binding the modified ligand to the surfaces of the CNPs through ligand exchange, so as to obtain the CNPs provided with modified surfaces. The CNPs have the characteristics of excellent dispersity, high stability, controllable enzymological activity and the like; the modified CNPs can be applied to the fields such as biological medicine and chemical engineering.

Description

technical field [0001] The invention belongs to the field of biomedical chemistry, and in particular relates to a method for surface modification of cerium nanoparticles, in particular to a method for covalently combining BP small molecules with PEG to modify the surface of CNPs synthesized by different methods , especially related to the surface modification of CNPs synthesized by microemulsion method and high temperature pyrolysis method. Background technique [0002] Cerium nanoparticles, in the present invention, "cerium nanoparticles" is also called "CNPs", because its surface Ce 3+ / C 4+ Coexist and thus behave like superoxide dismutase (Chem.Commun.2007, 1056–1058), oxidase (Angew.Chem.Int.Ed. .2010,46,2736–2738) enzymatic activity, making it useful in regenerative medicine (J.Mater.Chem.2010,20,8912-8919; Biomaterials2013,34,2194-2201), scavenging free radicals (Nanoscale2011,3 , 1411-1420; Chem.Soc.Rev.2010, 39, 4422-4432) and related diseases (Nat.Nanotechnol.20...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B22F1/00
Inventor 杨小超阳章友李蓉贺建董世武罗圣霖江虹白燕
Owner ARMY MEDICAL UNIV
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