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Nanoparticles as well as preparation method and application thereof

A nanoparticle and carboxyl technology, applied in the field of medicine, can solve the problems of limited treatment and increase tumor resistance, and achieve the effects of high biological safety, reducing drug resistance and prolonging survival.

Active Publication Date: 2020-09-01
SHANDONG UNIV QILU HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Accumulating evidence suggests that the genetic and epigenetic heterogeneity of GBM may underlie the current treatment limitations
Due to the existence of the blood-brain barrier (BBB), serious side effects and other factors, the strategy of single chemotherapy drugs in the treatment of glioma cannot achieve good clinical results, and even increase the drug resistance of tumors.

Method used

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  • Nanoparticles as well as preparation method and application thereof
  • Nanoparticles as well as preparation method and application thereof
  • Nanoparticles as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0102] Example 1 Preparation of si-GPX4@IONPs nanoparticles

[0103] In the first step, 1 mL of carboxyl-containing porous IONPs (10 mg / mL) was added to an aqueous solution of diethylpyrocarbonate (DEPC) at pH = 6, followed by 9.6 mg of EDC and 5.8 mg of NHS, and stirred at room temperature for 1 h. In the second step, before loading si-GPX4, the 5' end of the sense strand of si-GPX4 was modified with amino group and labeled with 5-carboxyfluorescein (FAM). si-GPX4 with different I / S ratios was added to the solution obtained in the first step for 30 min to obtain si-GPX4@IONPs, and the binding force was evaluated by agarose gel electrophoresis.

Embodiment 2

[0104] Example 2 Preparation of Pt+si-GPX4@IONPs nanoparticles

[0105] Operate under dark conditions, mix 10mg / mL si-GPX4@IONPs with 3mg / mL Pt and stir for 8 hours to make the two fully electrostatically adsorbed. The mixture was centrifuged at 1000 rpm with an ultrafiltration centrifuge tube (MWCO: 10kD) to remove free Pt to obtain Pt+si-GPX4@IONPs. The encapsulation efficiency and drug loading were detected by inductively coupled plasma mass spectrometry (ICP-MS).

Embodiment 3

[0106] Example 3 Preparation of FA / Pt+si-GPX4@IONPs nanoparticles

[0107] Operated under dark conditions, liposomes and DEPC H of 1mg / mL Pt+si-GPX4@IONP 2 o 2 The solutions were mixed and hydrated to obtain FA / Pt+si-GPX4@IONPs. The final solution was filtered through a 200nm polycarbonate membrane and purified by a Sephadex G-100 column, condensed and stored at 4°C for further use;

[0108] Among them, the liposome is composed of lipofectamine 2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol) 2000] (DSPE-PEG2k-FA) (molar ratio 6:1).

[0109] Among them, the preparation process of si-GPX4@IONPs, Pt+si-GPX4@IONPs, FA / Pt+si-GPX4@IONPs nanoparticles is as follows: figure 1 Shown; SEM and TEM images of IONPs, si-GPX4@IONPs, Pt+si-GPX4@IONPs nanoparticles figure 2 Shown; TEM image of FA / Pt+si-GPX4@IONPs nanoparticles image 3 Shown; The particle size distribution of IONPs, Pt+si-GPX4@IONPs, FA / Pt+si-GPX4@IONPs nanoparticles is as fol...

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Abstract

The invention belongs to the technical field of medicines, in particular to Pt+si-GPX4(at)IONPs and FA / Pt+si-GPX4(at)IONPs nano-particles as well as a preparation method and an application thereof. According to the invention, three therapeutic drugs, i.e., cis-platinum, si-GPX4 and IONPs, are combined into a whole; glioma cell death is jointly induced from two aspects of cell apoptosis and ferroptosis; in addition, the FA-modified liposome is used for wrapping three medicines, namely cis-platinum, si-GPX4 and IONPs, the advantages of good targeting property and high biocompatibility are achieved, a very good treatment effect on glioma is achieved, the defects of a traditional single chemotherapy medicine are overcome, and a multi-target combined chemotherapy method for glioma cells is provided.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a Pt+si-GPX4@IONPs nanoparticle, a FA / Pt+si-GPX4@IONPs nanoparticle and a preparation method and application thereof. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Glioma is considered one of the deadliest and most difficult to treat cancers. Glioma can be divided into 4 grades according to the degree of malignancy (WHO I, II, III and VI), and the most common glioma is type IV glioma, also known as glioblastoma (GBM). The current comprehensive treatment including surgical resection, chemotherapy and radiotherapy has limited curative effect on GBM patients, and the median s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/24A61K47/22A61K33/243A61K33/26A61P35/00A61K31/7105
CPCA61K9/5146A61K33/243A61K33/26A61K31/7105A61P35/00A61K2300/00
Inventor 倪石磊张玉霖王军鹏
Owner SHANDONG UNIV QILU HOSPITAL
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