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Preparation method and application of zero-valent iron delivery nanoparticles

A nanoparticle, zero-valent iron technology, applied in the field of biomedicine, can solve the problems of lack of research on zero-valent siderophore, reduced tumor cell inhibition rate, and high cost of precious metal Pt, and achieves easy production, simple preparation, and good biological safety. Effect

Active Publication Date: 2020-10-16
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the cost of precious metal Pt is too high, and there are biological safety hazards
Another work prepared the core-shell Fe 2 C nanoparticles, but the nanoparticle shell structure seriously hinders the iron release of the particles in the tumor microenvironment, resulting in a decrease in the tumor cell inhibition rate, which is difficult to meet expectations, so it is necessary to add additional hydrogen peroxide to improve the catalytic activity
[0009] Generally speaking, the current research on zero-valent siderophores is relatively scarce, and it is urgent to develop novel Fenton reaction catalytic iron nanoparticles with simple composition, clear structure, high stability, good biological safety, and high reactivity in this direction to achieve good antitumor effect

Method used

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  • Preparation method and application of zero-valent iron delivery nanoparticles
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  • Preparation method and application of zero-valent iron delivery nanoparticles

Examples

Experimental program
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Embodiment 1

[0045] Example 1: The schematic diagram of the preparation of open-pored zero-valent iron nanoparticles is as follows figure 1 Shown, preparation method comprises the steps:

[0046] (1) Synthesis of nano-Fe NPs (synthesis of zero-valent iron nanoparticle seeds): Accurately measure ODE (20mL) and OAm (0.3mL, 0.9mmol) and mix them in a four-necked flask, and continuously blow argon at 120°C In order to remove the oxygen used in the system, after 30 minutes, the temperature was raised to 180°C at 10°C / min, and Fe(CO) was injected through the syringe 5 (0.7 mL, 5.2 mmol). The reaction system was kept at 180° C. for 20 minutes, and then cooled to room temperature. Precipitate the particles with ethanol, centrifuge at 8000rpm for 5min, discard the supernatant, dissolve the precipitate in n-hexane, wash repeatedly three times, and collect the particles for later use.

[0047] (2) Controlled oxidation of Fe NPs: Add ODE (20mL) and (CH3) to a clean four-neck flask 3 NO (30mg, 0.4m...

Embodiment 2

[0050] Example 2: The surface of each nanoparticle is modified with PEG.

[0051] The dopamine-modified PEG is used to replace the oleylamine molecules wrapped on the surface of the nanoparticles to realize the PEGylated modification of the surface of the nanoparticles, so that they have good water solubility and biocompatibility. Weigh an appropriate amount of nanoparticles and dissolve in chloroform, add four times the mass of mPEG-DPA and stir for 12 hours. Chloroform was blown dry, and the mPEG-dopamine-modified nanoparticles were subsequently dried and dispersed in water, and then further purified by a PD-10 column.

Embodiment 3

[0052] Example 3: The surface of each nanoparticle is modified with iRGD.

[0053] Modification of the tumor-specific recognition molecule iRGD on the surface of nanoparticles can realize the active targeting of nanoparticles to tumor tissue, which is conducive to increasing the accumulation of nanoparticles in tumor tissue and improving the tumor treatment effect of nanoparticles and the diagnostic efficiency of magnetic resonance imaging. Concrete preparation process is as follows:

[0054] Utilize dopamined PEG and PEG-maleimide (PEG-MAL) to replace oleylamine on the surface of nanoparticles. After the reaction, dry the nanoparticles and dissolve them in water. Add an appropriate amount of iRGD-SH and place on a shaker Shake the reaction for 4h. After the reaction is completed, it is further activated through a PD-10 column.

[0055] The preparation of RGD-modified nanoparticles with an open pore structure in this example has been improved and optimized from the synthesis...

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Abstract

The invention discloses a preparation method of zero-valent iron delivery nanoparticles. According to the preparation method, carbonyl iron is used as a precursor, oleylamine is used as a surface ligand, octadecene and dibenzyl ether are used as solvents, trimethylamine oxide is used as an oxidant, and a series of core-shell structure nanoparticles with adjustable morphology, size and crystallinity are prepared by adopting an oil-phase high-temperature pyrolysis method and are used for activity protection and tumor delivery of zero-valent iron. The method comprises the following steps of (1) synthesizing zero-valent iron nanoparticle seeds; (2) synthesizing nanoparticles with different oxidation degrees; and (3) synthesizing nanoparticles with different opening degrees. Finally, the surfaces of the synthesized nanoparticles are modified through dopaminated polyethylene glycol, and iRGD targeting peptide is modified through chemical coupling, so that tumor targeting delivery is achieved. The zero-valent iron delivery nanoparticles synthesized and prepared by the method are controllable in morphology, good in stability and high in biocompatibility, have tumor targeting property, andcan be used for magnetic resonance imaging and tumor treatment.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a preparation method and application of zero-valent iron delivery nanoparticles. Background technique [0002] Cancer is a major disease that threatens human health and life. Its global morbidity shows a trend of rapid growth and its mortality rate remains high. Although clinical tumor treatment has entered the era of comprehensive treatment that complements each other with surgery, chemotherapy, radiotherapy, endocrine therapy, immunotherapy and small molecule targeted therapy. However, there are certain problems in the commonly used treatment methods, such as surgical treatment is not suitable for the treatment of advanced and metastatic tumors, chemotherapy has obvious toxic side effects, radiotherapy has great damage to normal tissues, and immunotherapy is expensive. Therefore, there is an urgent need to develop new therapeutic methods with low cost, easy production, hig...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K9/52A61K33/26A61K47/60A61K47/62A61K49/18A61P35/00C01G49/08B82Y5/00
CPCA61K33/26A61K47/60A61K47/62A61K47/6925A61K9/5115A61K49/183A61K49/186A61K49/1866A61P35/00B82Y5/00
Inventor 孙晓莲梁欢郭敬儒
Owner CHINA PHARM UNIV
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