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Application of Iron Oxide Nanoparticles in the Preparation of Drugs for Improving Erlotinib Resistance

A technology of iron oxide nanometer and drug resistance, which is applied in the direction of drug combination, antineoplastic drug, bulk delivery, etc., can solve drug resistance and other problems, achieve high biological safety, far-reaching clinical significance and promotion, and enhance anti-tumor The effect of cell proliferation

Active Publication Date: 2018-03-13
THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of the present invention is to find a kind of material that improves the drug resistance of erlotinib, find that the combined application of this material and erlotinib significantly inhibits the growth of tumors, thereby understanding the new medical application of this material, thereby solving the problem of erlotinib The problem of resistance to tinib in the treatment of small cell lung cancer

Method used

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  • Application of Iron Oxide Nanoparticles in the Preparation of Drugs for Improving Erlotinib Resistance
  • Application of Iron Oxide Nanoparticles in the Preparation of Drugs for Improving Erlotinib Resistance
  • Application of Iron Oxide Nanoparticles in the Preparation of Drugs for Improving Erlotinib Resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Embodiment 1: the making of iron oxide nanoparticles

[0016] Mix dextran, ferrous chloride, and ferric chloride at a mass ratio of 39.6:1:2.7, and react at 60°C for 1 hour, and slowly add an equal volume of ammonia water dropwise during the reaction. The reaction product was centrifuged at 12 000 r / min for 15 min, and the supernatant was taken and filtered with a 0.22um membrane filter. Continue at 12 000 r / min, remove the supernatant, wash with 150 mmol / L NaCl solution and resuspend.

[0017] Detection of the product: the diameter of the iron oxide nanoparticles of the product is below 10nm. In acidic conditions, the zeta potential of nanoparticles is positive; in neutral and alkaline conditions, the zeta potential of nanoparticles is negative.

Embodiment 2

[0018] Example 2: Anti-proliferation experiment of iron oxide nanoparticles on human non-small cell lung cancer A549

[0019] On the first day, 100ul of 5000 small cell lung cancer A549 cells were added to each well, and medium was added to make the volume 200ul. On the second day, after the cells adhered to the wall, different concentrations (2mM, 200uM, 20uM, 2uM, 200nM, 20nM, 2nM, 0.2nM, 0.02nM, 0.002nM) iron oxide nanoparticles treatment. Two days after treatment, 20 microliters of CCK-8 solution was added to each well. Continue to incubate in the cell culture incubator for 0.5-4 hours, and measure the absorbance at 450 nm.

[0020] Such as figure 1 As shown, different concentrations of iron oxide nanoparticles were used to treat lung cancer A549 cells, and the results showed that 2mM and 200uM iron oxide nanoparticles had a significant inhibitory effect on lung cancer A549 cells.

Embodiment 3

[0021] Example 3: Effect of iron oxide nanoparticles and erlotinib on the proliferation of human non-small cell lung cancer A549 and H358 cells

[0022] On the first day, 100ul of 5000 cells of non-small cell lung cancer A549 and H358 cells were added to each well, and culture medium was added to make the volume 200ul. On the second day, after the cells adhered to the wall, different concentrations of erlotinib (5uM, 10uM, 20uM, 40uM) and 200uM iron oxide nanoparticles treatment. On the corresponding days after treatment, 20 microliters of CCK-8 solution was added to each well. Continue to incubate in the cell culture incubator for 0.5-4 hours, and measure the absorbance at 450 nm.

[0023] Such as figure 2 and image 3 As shown, the combination of iron oxide nanoparticles and erlotinib inhibited the proliferation of human non-small cell lung cancer A549 and H358 cells. The results showed that iron oxide nanoparticles could significantly enhance the inhibitory effect of e...

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Abstract

The present invention discloses applications of iron oxide nanoparticles in preparation of a drug for improving erlotinib resistance, wherein a mass ratio of the iron oxide nanoparticles to the erlotinib is generally 1-40:1 and the consumption of the iron oxide nanoparticles in each day is not more than 10 mg / kg when the iron oxide nanoparticles are used for preparing the drug for improving erlotinib resistance. According to the present invention, lung cancer cells H 358 cultured in vitro and a drug resistance cell line A549 cultured in vitro are concurrently treated with the iron oxide nanoparticles and the erlotinib, and the results show that the anti-tumor-cell-proliferation effect can be significantly enhanced; further experiment results show that the tumor growth can be significantly inhibited through the combination of the iron oxide nanoparticles and the erlotinib, such that it is suggested that the iron oxide nanoparticles can enhance the sensitivity of the lung cancer cells on the erlotinib through the ERBB2, ERBB3, ERBB4 downstream signaling pathway; and the solving scheme is provided for the clinical treatment of the erlotinib resistant lung cancer patient.

Description

technical field [0001] The invention relates to the new pharmaceutical application of substances, in particular to the application of iron oxide nanoparticles in the preparation and improvement of drug resistance. Background technique [0002] Lung cancer is the most common malignant tumor in my country, and molecular targeted therapy is a new way to treat lung cancer. Erlotinib (English: Erlotinib) is currently the first-line targeted therapy for advanced non-small cell lung cancer, which significantly prolongs the survival of patients. Erlotinib has different therapeutic effects in different patients, and its key molecular marker is epidermal growth factor receptor (EGFR). In a study known as IPASS (EGFR Inhibitors Pan-Asian Study), EGFR small-molecule inhibitors were significantly superior to standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive lung adenocarcinoma, compared with EGFR mutation-negative patients. Inhibitors we...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/26A61K9/16A61P35/00A61K31/517
Inventor 唐敬群张美丽喻风雷向娟娟李桂源李征
Owner THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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