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2-(9-methylene anthracene) thiosemicarbazide and TAT modified gold nanoparticle drug delivery system and application

A technology of methylene anthracene and thiosemicarbazide, which is applied in the field of biomedicine, can solve problems such as the application limitation of chemotherapeutic drugs, and achieve the effects of good biocompatibility, low cytotoxicity and enhanced Raman signal.

Inactive Publication Date: 2017-07-28
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Due to the multidrug resistance of tumor cells, the clinical application of chemotherapy drugs is greatly limited

Method used

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  • 2-(9-methylene anthracene) thiosemicarbazide and TAT modified gold nanoparticle drug delivery system and application
  • 2-(9-methylene anthracene) thiosemicarbazide and TAT modified gold nanoparticle drug delivery system and application
  • 2-(9-methylene anthracene) thiosemicarbazide and TAT modified gold nanoparticle drug delivery system and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 ANS-TAT-AuNPs 3.8nm and its preparation method

[0034] The particle size synthesized in this example is a gold nanometer drug-carrying system of 3.8nm, and the preparation method comprises the following steps:

[0035] (1) Preparation of gold nanoparticles coated with citrate ions by sodium borohydride reduction method: in 0.25mM HAuCl 4 and 0.25mM sodium citrate mixed aqueous solution 200mL, add ice-bathed 0.1M NaBH 4 Aqueous solution 6mL, stirred at room temperature for 2h in the dark;

[0036] (2) TAT modification: Add 1mL of 1mM polypeptide TAT aqueous solution to 197mL of the solution prepared in step (1), and stir at room temperature for 1min;

[0037] (3) Coating of 2-(9-methylene anthracene) thiosemicarbazide: 15 mL of DMSO solution of 0.2 mg / mL 2-(9-methylene anthracene) thiosemicarbazide was added to the solution prepared in step (2), Stir at room temperature in the dark for 2 hours; let stand, wash several times with water, centrifuge, and quan...

Embodiment 2

[0039] Example 2 ANS-TAT-AuNPs 22.1n and its preparation method

[0040] The particle size synthesized in this example is a gold nano drug-carrying system of 22.1nm. The preparation method comprises the following steps:

[0041] (1) Preparation of gold nanoparticles coated with citrate ions by sodium citrate reduction method: in 0.23mM HAuCl 4 Add 10mL of 1% sodium citrate aqueous solution to 192mL aqueous solution, stir, reflux for 2h, and set aside;

[0042] (2) TAT modification: add 43.95 μL of 0.1 mM polypeptide TAT aqueous solution to the solution prepared in step (1), and stir at room temperature for 1 min;

[0043] (3) Coating of 2-(9-methyleneanthracene)thiosemicarbazide: 10 mL of 0.05 mg / mL 2-(9-methyleneanthracene) thiosemicarbazide in DMSO and 0.2 mg / mL 2-(9-methanthracene) Add 5 mL of DMSO solution of methyl anthracene) thiosemicarbazide to the solution prepared in step (2), and stir at room temperature in the dark for 2 h; let stand, wash several times with water...

Embodiment 3

[0046] Example 3 Determination of drug resistance index of ANS-TAT-AuNPs

[0047] The drug resistance index of ANS-TAT-AuNPs with different particle sizes was measured, and the experimental method adopted the conventional MTT method.

[0048] 1. Sample preparation: Dissolve ANS-TAT-AuNPs in a mixed solution of DMSO / water and dilute with culture medium.

[0049] 2. Cell lines: MCF-7 sensitive cells and MCF-7 / ADR drug-resistant cells, the above cell lines are all frozen and passaged by our laboratory.

[0050] 3. Culture medium: RPMI 1640+10% fetal bovine serum+double antibody (penicillin, streptomycin each 100U / mL).

[0051] 4. Other materials: automatic microplate reader, model PerkinElmer EnSpire 2300Multilabel PlateReader, 96-well plate.

[0052] 5. Test method: MTT method. Add 5×10 per well in a 96-well plate 4 100 μL / mL of cell suspension, placed at 37 °C, 5% CO 2 in the incubator. After 24 hours, the culture medium was aspirated and replaced with drug-containing med...

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Abstract

The invention provides a 2-(9-methylene anthracene) thiosemicarbazide and TAT modified gold nanoparticle drug delivery system. The 2-(9-methylene anthracene) thiosemicarbazide and TAT modified gold nanoparticle drug delivery system has the advantages that a gold nanosphere drug delivery system with the particle size being 3.8nm (sodium borohydride reduction method) and a gold nanosphere drug delivery system with the particle size being 22.1nm (sodium citrate reduction method) are built, the surfaces of the systems are modified with polypeptide TAT, the systems modified by the polypeptide TAT are used as the carriers of 2-(9-methylene anthracene) thiosemicarbazide, the fact that the drug-resistance index of large-particle-size gold nanospheres to drug-resistance cells is smaller is discovered through the antitumor activity evaluation of MCF-7 sensitive cells and MCF-7 / ADR drug-resistance cells, and the fact shows that large-particle-size carriers are more suitable for tumor drug resistance treatment and the 22.1nm gold nanospheres have an enhancing effect on the Raman signal of the 2-(9-methylene anthracene) thiosemicarbazide and can be used for cellular-level Raman imaging.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a 2-(9-methyleneanthracene) thiosemicarbazide and TAT-modified gold nanometer drug-carrying system and its application. Background technique [0002] Due to unique physical and chemical properties, such as local surface plasmon resonance, good biocompatibility, and simple and effective surface modification, gold nanoparticles have received extensive attention. They are widely used in biosensors, drug delivery, and tumor targeting. Diagnosis and treatment and other fields have shown great application potential and prospects. [0003] RGRKKRRQRRR is a classic cell membrane-penetrating peptide derived from HIV-1 TAT protein, which is rich in arginine (amino group). The high density of positive charges enables it to interact strongly with the head group of phospholipids, thereby being able to pass through the cell membrane , so it is widely used in the construction of nano-drug loading sy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K31/175A61K47/52A61K47/64A61K47/69A61P35/00G01N21/65
Inventor 房晨婕王瑞慧白洁
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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