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Drug-resistant cisplatin mineralization liquid and preparation method and application thereof

A drug-resistant, cisplatin technology, applied in the field of coordination chemistry and pharmacy, can solve the problems of not many drug-resistant tumor treatment methods, destroying normal cells, non-degradable, etc., to improve drug efficacy, obvious curative effect, and enhance inhibitory effect. Effect

Inactive Publication Date: 2015-04-22
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these nanomaterials have biological safety problems. They are often non-degradable under physiological conditions, and the materials themselves may have the ability to destroy normal cells, which may cause relatively large side effects.
Therefore, the modification and transformation of platinum-based drugs has been researched, but there are still not many effective treatments for drug-resistant tumors.

Method used

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  • Drug-resistant cisplatin mineralization liquid and preparation method and application thereof
  • Drug-resistant cisplatin mineralization liquid and preparation method and application thereof
  • Drug-resistant cisplatin mineralization liquid and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0036] The present invention adopts the technology of in situ biomineralization, in the improved DMEM medium (also known as low-chloride medium), utilizes the condition of cell culture, reacts and generates the nano solidified hydrolysis intermediate of cisplatin, and carries out the formation For morphology, particle size and elemental analysis, see respectivelyfigure 1 , figure 2 , image 3 .

[0037] Specific steps are as follows:

[0038] 1. Hydrolysis balance and substitution of cisplatin

[0039] 10 groups of cisplatin (0, 2.188, 3.125, 4,375, 6.250, 8.750, 12.500, 17.500, 25.000, 35.000μM) were added to 2ml low chloride medium and equilibrated for 24 hours. The conditions were 37°C, 95% air atmosphere, 5 %CO 2 , the pH is 7.2, the carbonate and phosphate in the low chloride medium will spontaneously replace the chlorine ligands in the molecule to complete the modification of the drug, and about 10% of the cisplatin molecules enter the nano-cured intermediate, the l...

Embodiment 2

[0044] The invention uses fluorescent molecule isothiocyanate FITC to mark bovine serum albumin BSA, and then marks the nano-cured intermediate, and tracks the process and efficiency of the material entering cells. The results showed that the nanoimmobilized cisplatin hydrolysis intermediates entered cells through lysosome-mediated endocytosis, rather than Ctr1-mediated membrane protein transport. In addition, this internalization method is very efficient. Flow cytometry was used to detect the efficiency of FITC-BSA-labeled nano-immobilized cisplatin hydrolysis intermediates entering cells. The results showed that within 1 hour, most of the cells were completed. ingest, see Figure 4 . The specific operation is as follows:

[0045] 1. Marking of BSA

[0046] 500mg of BSA was added to 2ml of 0.25M sodium bicarbonate (pH=9.8) buffer solution, 9mg of FITC dissolved in DMSO was added to the above protein solution, and stirred slowly overnight at 4°C. The resulting FITC-BSA was...

Embodiment 3

[0053] The present invention uses the MTT test method to detect the poisonous effect of cisplatin and mineralized modified cisplatin (ie, cisplatin mineralization solution) on A549 and its drug-resistant cell A549 / DDP. The results showed that the mineralized modified cisplatin solution showed a significant drug effect enhancement, and for the A549 / DDP cells whose cisplatin effect was not obvious, the mineralized modified cisplatin could also show a significant drug effect, which was basically equivalent to For levels of sensitive cell lines exposed to cisplatin, see Figure 5 , calcium ions (0, 2, 4, 6, 8, 10 mM) were introduced into the low chloride medium without adding cisplatin to form a mineralization modification solution, and the modification solution showed negligible cytotoxicity, see Image 6 .

[0054] 1. A549 and A549 / DDP cells were treated with 1×10 4 The density of cells / well was inoculated in 96-well plate respectively, and after 24 hours, cisplatin (100 μl) a...

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Abstract

The invention discloses a preparation method for drug-resistant cisplatin mineralization liquid. The method comprises the following steps: (1) cisplatin is added in an improved DMEM culture medium, and is reacted under the similar physiological conditions to obtain substituted midbody solution; (2) calcium-contained inorganic salt is added in the obtained substituted midbody solution, and is reacted under the similar physiological conditions to obtain a nano cured midbody system; and (3) bovine serum albumin is added in the obtained nano cured midbody system to obtain the cisplatin mineralization liquid. The invention further discloses the cisplatin mineralization liquid produced by the preparation method, and application thereof, wherein the cisplatin mineralization liquid has stronger lethality to tumor cells, and has remarkable curative effect on tumors which are difficultly cured by the cisplatin and have obvious drug resistance.

Description

technical field [0001] The invention belongs to the fields of coordination chemistry and pharmacy, and in particular relates to a drug-resistant cisplatin mineralization solution and a preparation method and application thereof. Background technique [0002] Tumor treatment has always been an insurmountable problem in modern medicine. Cisplatin is an important means for the treatment of tumors. However, the problem encountered by this method is: with the progress of drug chemotherapy, tumors will show acquired This resistance makes the tumor tissue no longer sensitive to chemotherapy drugs, resulting in drug resistance, which eventually leads to the failure of chemotherapy. [0003] The reasons for drug resistance may be as follows: (1) insufficient uptake of platinum-based drugs by cells; (2) rich-NH metabolized in cells 2 And -SH small molecules and proteins can complex platinum drugs, making them unable to bind to DNA to play a role; (3) after platinum drugs and DNA form...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C01B21/092A61K33/24A61P35/00
Inventor 陈伟肖云刘雪瑶陈燕红章娇娇徐旭荣唐睿康
Owner ZHEJIANG UNIV
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