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Targeted polymer micelle magnetic nanoparticle, and preparation method and application thereof

A technology of magnetic nanoparticles and polymer glue, applied in drug delivery, preparations for in vivo tests, emulsion delivery, etc., can solve the problem of difficult diagnosis of pancreatic tumors, and achieve the effect of improving the ability of independent innovation

Inactive Publication Date: 2015-08-05
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these imaging methods are also difficult to diagnose pancreatic tumors less than 2 cm in diameter

Method used

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  • Targeted polymer micelle magnetic nanoparticle, and preparation method and application thereof
  • Targeted polymer micelle magnetic nanoparticle, and preparation method and application thereof
  • Targeted polymer micelle magnetic nanoparticle, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment one: Synthesis of CKAAKN-PEG-PLGA grafts

[0026] Dissolve commercially available polylactic acid-glycolic acid (PLGA, Mw: 8000) in a certain amount of dimethyl sulfoxide (DMSO, Mw: 78.13) solution, add a certain amount of N,N'-dicyclohexylcarbodi Imine (DCC, Mw: 206.18) and N-hydroxysuccinimide (NHS, Mw: 115.09) were reacted with magnetic stirring at room temperature for 24 h under the protection of argon, and slowly added dropwise a certain amount of polyethylene glycol ( PEG, Mw:1500) in DMSO solution, continue to react for 6 h, then dissolve with acetone (concentration: 20mg / mL) after dialysis, centrifugation, and freeze-drying, then redissolve with deionized water, and obtain PEG- PLGA copolymer. Dissolve an appropriate amount of PEG-PLGA copolymer, CKAAKN polypeptide and DCC in a certain amount of DMSO solution, and react with magnetic stirring for 8 hours at room temperature, mix with a certain amount of deionized water, dialyze, centrifuge, and dry...

Embodiment 2

[0029] 1. Preparation of polymer micellar magnetic nanoparticles and determination of their physical and chemical properties

[0030] CKAAKN-PEG-PLGA-USPIO was prepared by solvent diffusion and dialysis. The specific method is: a certain amount of oil-soluble Fe 3 o 4 (particle size 5 nm, concentration 5 mg / ml) magnetic nanoparticle solution as the core was ultrasonically dispersed in F-68 solution (Poloxamer 188, 0.1 %, w / v), and the probe was continuously ultrasonicated for 30 min (600 w, After working for 2 s and resting for 3 s), 10 mg / ml oleic acid ethanol solution was added, and the probe was sonicated for 5 min to obtain Fe 3 o 4 nanoparticle dispersion. Weigh a certain amount of CKAAKN-PEG-PLGA and dissolve it in an appropriate amount of deionized water; under the condition of ultrasonic stirring, add a certain amount of Fe 3 o 4 The nanoparticle dispersion was subjected to continuous ultrasonication for 10 min, and then rotary evaporated in a water bath at 60°C ...

Embodiment 3

[0043] Embodiment three: MRI Scanning of Polymer Micellar Magnetic Nanoparticle Samples

[0044] The magnetic susceptibility of the polymeric micellar magnetic nanoparticles was measured by measuring the change in the T2* relaxation time of the magnetic resonance scan. The prepared polymer micellar magnetic nanoparticle suspensions with different concentrations (0, 1, 10, 15, 25, 50, 75, 100 μg / ml) were respectively filled into 2.0 ml Eppendorf tubes, placed in water-filled In a test tube box, the scan was performed with an eight-channel head coil under GE 3.0T whole-body magnetic resonance.

[0045] see Image 6 , the results show that with the increase of the final iron concentration in the polymer micelle magnetic nanoparticle suspension on the ESWAN image, the T2* signal intensity gradually decreases, indicating that the polymer micelle magnetic nanoparticles prepared in this experiment have negative reinforcement. Effect, that is, within a certain concentration range,...

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Abstract

The invention provides a polymer micelle magnetic nanoparticle having a selective specific targeting function on pancreas cancer. A preparation method of the polymer micelle magnetic nanoparticle comprises the following steps: carrying out an amide reaction on a carboxyl group on a CKAAKN polypeptide and an amino group on the carboxyl group on polyethylene glycol-polylactic acid-glycolic acid, coupling the CKAAKN polypeptide to prepare a CKAAKN-PEG-PLGA graft product, and carrying out an aqueous solvent diffusion technology with a Fe3O4 magnetic nanoparticle as a targeting marker material to prepare the polymer micelle magnetic nanoparticle. The preparation method has the advantages of reasonable design, convenient operation and low cost. The polymer micelle magnetic nanoparticle provided by the invention has high magnetic Fe3O4 nanoparticle wrapping ability, has the advantages of good stability and dispersibility, small particle size and uniform dispersion, can enhance the targeted uptake ability of the pancreas cancer to improve the uptake rate, and can be used as a pancreas cancer targeted magnetic resonance specific contrast agent to realize safe and rapid pancreas cancer targeted molecule image imaging.

Description

technical field [0001] The invention belongs to a compound preparation method, relates to a synthesis method of polymer micelle magnetic nanoparticles, in particular to a targeted polymer micelle magnetic nanoparticle, which can be used as a magnetic resonance contrast agent specifically targeting pancreatic cancer at the nanoscale in biomedicine applications in the field. Background technique [0002] At present, the diagnostic methods of pancreatic cancer mainly include the detection of tumor markers and imaging diagnosis. Carbohydrate antigen CA19-9 is currently the most widely used and recognized tumor marker for the diagnosis of pancreatic cancer, but it can also be positive in chronic pancreatitis and other diseases, lacking sufficient sensitivity and specificity. Commonly used imaging methods for the diagnosis of pancreatic cancer include computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), and positron emission tomography (PE...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14A61K49/12A61K49/18
Inventor 朱修良汪祖华余日胜杜永忠揭丽勇陈英钱姿桦杨丽
Owner ZHEJIANG UNIV
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