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Ultra-small gold nanoparticle for tumor cell mitochondria targeting and rapid kidney metabolism

A nanoparticle and tumor cell technology, applied in antitumor drugs, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc. Lack of tumor or organelle targeting function, etc., to achieve the effect of improving the enrichment degree and residence time, good biological safety, and beneficial to metabolism

Active Publication Date: 2020-03-17
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, such nanomaterials lack tumor or organelle targeting functions, are not conducive to accumulation in tumor tissues and interact with specific organelles, and have poor radiosensitization effects.

Method used

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  • Ultra-small gold nanoparticle for tumor cell mitochondria targeting and rapid kidney metabolism
  • Ultra-small gold nanoparticle for tumor cell mitochondria targeting and rapid kidney metabolism
  • Ultra-small gold nanoparticle for tumor cell mitochondria targeting and rapid kidney metabolism

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] 1) Add the peptide CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK to 10 mL of chloroauric acid (1 mM) solution, and stir vigorously at room temperature for 15 minutes to make the peptide concentration reach 2 mM. Sodium borohydride was added to bring the concentration to 10 mM. After stirring vigorously at room temperature for 0.5-1 hour, a polypeptide-stabilized ultra-small gold nanoparticle suspension is obtained. Its transmission electron microscope pictures are shown in figure 1 .

[0044] 2) Put 10mL of the gold nanoparticle suspension obtained in step 1) into a dialysis centrifuge tube (molecular weight cut-off 3000Da), centrifuge at 5000 rpm for 10 minutes, and the solution containing excess polypeptide ligand and sodium borohydride will be collected at the bottom of the centrifuge tube, The ultra-small gold nanoparticles obtained by concentration are retained on the upper part of the centrifuge tube.

[0045] 3) The gold nanoparticles (Au@Res Peptide, 100 μg / mL) obtained ...

Embodiment 2

[0049] Same as Example 1, the difference lies in step 1): Add polypeptide CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK to 10mL of chloroauric acid (1mM) solution, stir vigorously at room temperature for 15 minutes, so that the concentration of the polypeptide reaches 0.25, 0.5, 1.0, 2.0mM respectively. Sodium borohydride was added to bring the concentration to 10 mM. After stirring vigorously at room temperature for 0.5-1 hour, the peptide-stabilized ultra-small gold nanoparticle suspension prepared under different raw material feeding ratios is obtained. The results of the relationship between the size of gold nanoparticles and the proportion of raw materials can be found in figure 2 . As the ratio of polypeptide to chloroauric acid gradually increased, the particle size of the obtained nano-gold gradually decreased. It can be seen that to obtain gold nanoparticles with a particle size below 5.5nm, the molar ratio of polypeptide to chloroauric acid needs to be 1-2:1.

Embodiment 3

[0051] Same as Example 1, the difference lies in step 1): in 10mL of chloroauric acid (1mM) solution, add different polypeptides respectively:

[0052] (1) CCEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK;

[0053] (2) CEKEKVFrFKFrFKVGFLGVEKEKEKEKEKEK;

[0054] (3) CVFrFKFrFKVGFLGVEKEKEKEKEKEK;

[0055] (4) CEKVFrFKFrFKVGFLGVEKEKEKEKEKEK.

[0056] Vigorously stir at room temperature for 15 minutes to make the peptide concentration reach 2.0 mM. Sodium borohydride was added to bring the concentration to 10 mM. After stirring vigorously at room temperature for 0.5-1 hour, a stable ultra-small gold nanoparticle suspension of different polypeptides is obtained. The results of the relationship between the size of gold nanoparticles and peptides can be found in Image 6 . It can be seen that all four kinds of polypeptides can obtain gold nanoparticles with a particle size below 5.5nm.

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Abstract

The invention discloses an ultra-small gold nanoparticle with characteristics of tumor cell mitochondria targeting and rapid kidney clearance. The diameter of the nanoparticle is 2.5 to 5.5 nm. The nanoparticle is prepared by modifying the surface of a gold nanoparticle with cell-penetrating peptide. The cell-penetrating peptide is composed of an FrFKFrFK sequence, a VGPLGV sequence and an EKEKEKEKEKEK sequence. According to the invention, the ultra-small gold nanoparticle is small in size, is beneficial to kidney metabolism and has good biological safety; the multifunctional responsive surface is stable under normal physiological conditions, and internal mitochondria targeting molecules are exposed after the multifunctional responsive surface responds to a tumor microenvironment, so thatthe multifunctional responsive surface is efficiently swallowed by liver tumor cells and targets mitochondria; the enrichment degree of the gold nanoparticle in tumors is increased, and the residencetime of the gold nanoparticle in tumors is prolonged; the gold nanoparticle is in contact with mitochondria, so that the structure and the function of the mitochondria can be destroyed more effectively under the irradiation of radioactive rays; and a better radiotherapy sensitization effect is achieved.

Description

[0001] (1) Technical field [0002] The invention relates to an ultra-small gold nanoparticle with the characteristics of tumor cell mitochondria targeting and rapid renal clearance, its preparation method and application. [0003] (2) Background technology [0004] Radiation therapy for tumors is a local treatment method that uses radiation to treat tumors. Radiation includes α, β, γ rays produced by radioactive isotopes and x-rays, electron beams, proton beams and other particle beams produced by various x-ray therapy machines or accelerators. The role and status of radiotherapy in tumor treatment has become increasingly prominent, and it has become one of the main means of treating malignant tumors. About 70% of cancer patients need radiation therapy in the course of cancer treatment, and about 40% of cancers can be cured by radiation therapy. However, due to the large dose required for radiotherapy and a certain course of treatment, the problem of side effects during the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/64A61P35/00
CPCA61K41/0057A61K47/64A61P35/00
Inventor 吴李鸣毛峥伟羊红玉冯靖祎
Owner ZHEJIANG UNIV
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