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PEGylated metal nano-composite as well as preparation method and application thereof

A PEGylation and metal nanotechnology, applied in the field of metal nanocomposites, the preparation of PEGylated metal nanocomposites, and the field of PEGylated metal nanocomposites, can solve the problem of reduced clinical application prospects, protein denaturation, Complex purification steps, etc., to achieve good therapeutic and diagnostic effects, good biocompatibility, and simple synthesis methods.

Pending Publication Date: 2021-03-26
GUANGDONG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, these large molecules are expensive, with complex and costly purification steps
When administered in vivo, this can lead to serious problems, for example, in order to make biomacromolecules more suitable for in vivo delivery of metal ions, surface modification with targeting moieties such as ligands and monoclonal antibodies must be carried out
However, the clinical prospect of this strategy is greatly reduced by the complex chemistry involved in the preparation process due to low reaction controllability often leading to protein denaturation, etc.
Therefore, it is a great challenge to realize the transport of metal ions while reducing the cost and complicated preparation process, thereby improving clinical translation.

Method used

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  • PEGylated metal nano-composite as well as preparation method and application thereof
  • PEGylated metal nano-composite as well as preparation method and application thereof
  • PEGylated metal nano-composite as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] (1) Synthesis of diblock copolymers

[0046] 1) Add 10 mol of sodium hydride (NAH, containing 60% mineral oil) into a 100 mL Schlenk flask containing 10 mL of anhydrous tetrahydrofuran, stir for about 0.5 h, stop stirring, and remove the upper transparent liquid with a pipette;

[0047]2) Add dry macromolecular initiator 1mol of mPEG 113 , the AGE monomer of 20mol and 100ml toluene are added to step 1) in the system, in N 2 Under atmosphere, the reaction temperature was 100°C, and the reaction time was 12h. After the reaction was over, 1 mL of ethanol was added to terminate the polymerization, and then precipitated with 100 mL of ether to obtain an intermediate product. The product H NMR spectrum was as follows: figure 1 shown;

[0048] 3) 1 mol of the intermediate product and 18 mol of 3-mercaptopropionic acid were dissolved in a round-bottomed quartz flask containing 100 mL of THF, and slowly bubbled with nitrogen for 30 minutes to eliminate dissolved oxygen, and t...

Embodiment 2

[0053] (1) Synthesis of diblock copolymers

[0054] 1) Add 20 mol of sodium hydride (NAH, containing 60% mineral oil) into a 100 mL Schlenk flask containing 10 mL of anhydrous tetrahydrofuran, stir for about 1 hour, stop stirring, and remove the upper transparent liquid with a pipette;

[0055] 2) Add dry macromolecular initiator 1mol of mPEG 113 , the AGE monomer of 40mol and 100ml toluene are added to step 1) in the system, in N 2 Under atmosphere, the reaction temperature was 100°C, and the reaction time was 24h. After the reaction, add 1mL ethanol to terminate the polymerization, and then precipitate with 100mL ether to obtain the intermediate product;

[0056] 3) 1 mol of the intermediate product and 36 mol of 3-mercaptopropionic acid were dissolved in a round-bottomed quartz flask containing 100 mL of THF, and slowly bubbled with nitrogen for 30 minutes to eliminate dissolved oxygen, and then at room temperature, under ultraviolet light ( 254nm, 1.29mWcm -2 ) under r...

Embodiment 3

[0061] (1) Synthesis of diblock copolymers

[0062] 1) Add 30 mol of sodium hydride (NAH, containing 60% mineral oil) into a 100 mL Schlenk flask containing 10 mL of anhydrous tetrahydrofuran, stir for about 1.5 h, stop stirring, and remove the upper transparent liquid with a pipette;

[0063] 2) Add dry macromolecular initiator 1mol of mPEG 113 , the AGE monomer of 60mol and 100ml toluene are added to step 1) in the system, in N 2 Under atmosphere, the reaction temperature was 100°C, and the reaction time was 36h. After the reaction, add 1mL ethanol to terminate the polymerization, and then precipitate with 100mL ether to obtain the intermediate product;

[0064] 3) 1mol of the intermediate product and 54mol of 3-mercaptopropionic acid were dissolved in a round-bottomed quartz flask containing 100mL of THF, and slowly bubbled with nitrogen for 30 minutes to eliminate dissolved oxygen, and then at room temperature, under ultraviolet light ( 254nm, 1.29mWcm -2 ) under react...

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Abstract

The invention discloses a PEGylated metal nano-composite as well as a preparation method and application thereof, and aims to provide the PEGylated metal nano-composite. A two-block polymer of the PEGylated metal nano-composite can adsorb various metal ions to form a corresponding nano-composite, so that the toxicity of free metal ions is reduced; and the internal circulation time can be prolonged, so that the nano-composite can be accumulated at tumor parts better, and the nano-composite has excellent tumor therapy and imaging effects. According to the technical scheme, the PEG diblock polymer and metal ions are subjected to electrostatic adsorption to obtain the PEG modified metal nano-composite.

Description

technical field [0001] The invention discloses a metal nanocomposite, specifically, a PEGylated metal nanocomposite. The present invention also discloses the preparation method and application of the PEGylated metal nanocomposite, which belongs to nanomedicine formulation field. Background technique [0002] Many metal ions play crucial roles in biological processes, such as the regulation of enzyme activity, inflammatory responses, cellular physiological behavior, and protein synthesis. Therefore, metal ions have increasingly important applications in the field of biomedicine, including disease treatment, drug delivery, imaging diagnosis, biocatalysis, biosensors, artificial muscles, etc. For example, platinum (Pt) compounds are among the most widely used clinical drugs for the treatment of advanced cancers. Clinically, metal ions play a common role as diagnostic agents, with metal radionuclides in CT imaging and paramagnetic metal complexes in magnetic resonance imaging ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K41/00A61K49/18A61P35/00B82Y5/00B82Y20/00B82Y25/00B82Y30/00B82Y40/00
CPCA61K47/61A61K41/0052A61K49/1818A61P35/00B82Y5/00B82Y30/00B82Y40/00B82Y20/00B82Y25/00
Inventor 陈泽丰何燕陈霓平曾耀勋刘旭杰王亚坤潘振星卞旺青袁炯鹏
Owner GUANGDONG UNIV OF TECH
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