Chiral nanometer fiber and its preparation method and use

A nanofiber and chiral technology, applied in the field of biomedicine, can solve the problems of lack of anti-tumor activity, strong hepatotoxicity, poor tumor suppression effect, etc., achieve inhibition of invasion and migration activity, good invasion and migration activity, and avoid toxic side effects Effect

Inactive Publication Date: 2015-10-14
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although a variety of HSP90 inhibitors have been discovered and artificially synthesized, these inhibitors still have shortcomings
For example, GA has the characteristics of poor water solubility, non-specific distribution in the body, and strong liver toxicity; 17-AAG also ha...

Method used

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  • Chiral nanometer fiber and its preparation method and use
  • Chiral nanometer fiber and its preparation method and use
  • Chiral nanometer fiber and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1: Preparation of Zn-Asp chiral nanofibers

[0038] (1) Preparation of amino acid solution: Weigh 133 mg of aspartic acid and dissolve it in 6 mL of absolute ethanol, add 1 mL of 2 mmol of sodium hydroxide aqueous solution to prepare 1 mmol of aspartic acid solution;

[0039] (2) Preparation of zinc nitrate solution: take 595 mg of zinc nitrate hexahydrate and dissolve it in 2 mL of ultrapure water to prepare 2 mmol of zinc nitrate solution;

[0040] (3) Titrate the aspartic acid solution with the zinc nitrate solution under stirring conditions, react the mixture on the water-absolute ethanol interface for 14 days, then wash with 10mL of anhydrous methanol three to five times, and put it in a vacuum drying oven Set aside to dry.

[0041] It can be seen from Figure 1 that Zn-Asp chiral nanofibers are fibrous, with a diameter of about 150nm and a length of 200-500μm.

Embodiment 2

[0042] Example 2: Interaction of Zn-Asp chiral nanofibers and tumor-associated proteins

[0043] 1. Interaction of Zn-Asp chiral nanofibers with HSP90

[0044] 200 μg Zn-Asp chiral nanofibers were incubated with 1 mL of purified recombinant protein HSP90 containing 2, 4, 8, 16, 24, 32, 48 and 72 μg at 37°C for 1 hour, centrifuged to discard the supernatant, and washed with PBS buffer After 3 times, the final pellet was resuspended with 2× loading buffer, then run for SDS-PAGE electrophoresis and stained with Coomassie brilliant blue.

[0045] 2. Zn-Asp chiral nanofibers interact with tumor cells

[0046] (1) The tumor cells were inoculated in serum-free DMEM medium, and after culturing for 48 hours, the supernatant was taken and labeled as sample SF;

[0047] (2) Inoculate tumor cells in serum-free DMEM medium, culture for 24 hours, add 200 μg / mL Zn-Asp chiral nanofibers to the medium and culture for another 24 hours, take the supernatant and mark it as sample SF+D (S) and ...

Embodiment 3

[0051] Example 3: Inhibition of Zn-Asp Chiral Nanofibers on Tumor Cell Proliferation, Migration and Invasion

[0052] Add 200 μg / mL Zn-Asp chiral nanofibers to 1% FBS cell culture medium and 10% FBS cell culture medium respectively, incubate the cells for 24 hours, and set up a parallel control group without chiral nanofibers in the cell culture medium , and then detect changes in cell viability, migration, and invasion.

[0053] As can be seen from Figure 3, (a) and (b) show that D- / L-Zn-Asp chiral nanofibers can bind HSP90, and show a significant concentration-dependent effect; (c) D- / L-Zn -Asp chiral nanofibers were also able to bind different gelatinases: MMP-9 polymers, MMP-9 precursors, MMP-2 precursors and active forms of MMP-2.

[0054] As can be seen from Figure 4, (a) shows that 200 μg / mL of D- / L-Zn-Asp chiral nanofibers cause 54% inhibition of cell migration; (b) shows that 200 μg / mL of D- / L-Zn- Asp chiral nanofibers caused 78% and 74% inhibition of cell invasion,...

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Abstract

The invention relates to the field of biological medicines and especially relates to a chiral nanometer fiber and its preparation method and use. The chiral nanometer fiber raw material mainly comprises zinc ions and chiral amino acid. The diameter of the chiral nanometer fiber is in a range of 120-160nm. The chiral nanometer fiber can be used for preparation of drugs for treating and preventing tumor cells. The chiral nanometer fiber can influence extracellular HSP90 functions thereby influencing an extracellular HSP90 related signal path, can well inhibit tumor invasion and migration activity, does not enter into cells, and does not influence cell normal physiological functions. When the chiral nanometer fiber is degraded in vivo, the degraded ingredient zinc ions and aspartic acid have very good biocompatibility and does not damage the body at an appropriate treatment concentration.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a chiral nanofiber and its preparation method and application. Background technique [0002] Heat shock protein (Heat Shock Protein, HSP) is an important regulatory protein in cells, which is involved in the physiological processes of various cells, such as cell proliferation, maintenance of cell cycle, etc.; moreover, HSP can also prevent protein denaturation And promote denatured protein refolding, protect cells under stress from damage. Subsequent studies have found that HSP not only participates in the physiological metabolic process of normal tissue cells, but also plays a key role in the development and deterioration of tumors. As an important member of the HSP protein family, HSP90 is closely related to most tumor-related features, including: persistent proliferation signals, evasion of growth inhibition, induction of angiogenesis, activation of invasion and metastasis, resista...

Claims

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Application Information

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IPC IPC(8): D01F9/00A61K33/30A61K31/198A61P35/00C12Q1/02B82Y30/00B82Y40/00
Inventor 宫建茹辛琪张海辉
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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