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Fe<3+/2+>-NO donor mixed-valence coordination polymer and application thereof

A coordination polymer and donor technology, applied in the fields of biomedical technology and nanotechnology, can solve the problems of restricting research and development and clinical application, and achieve the effect of high water solubility and stability

Active Publication Date: 2019-02-22
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the above problems limit the further development and clinical application of this NO donor as an antitumor drug.

Method used

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  • Fe&lt;3+/2+&gt;-NO donor mixed-valence coordination polymer and application thereof
  • Fe&lt;3+/2+&gt;-NO donor mixed-valence coordination polymer and application thereof
  • Fe&lt;3+/2+&gt;-NO donor mixed-valence coordination polymer and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1Fe 3+ / 2+ -NO donor mixed-valent coordination polymerized nanoparticles (Fe 3+ / 2+ - Construction of BPDB-NCP)

[0040] 1. NO donor 1,5-bis(L-proline azo-O 2 -)-2,4-dinitrobenzene synthesis, the synthetic route is as follows figure 1 As shown in A.

[0041] (a) : L-(+)-prolinol is dissolved in anhydrous ether, NaOMe / MeOH is added, placed in a high-pressure reactor, and nitrogen (N 2 ) to replace the air, then introduce NO gas, and seal the reactor for 36 hours. After the reaction, anhydrous diethyl ether was added to the reaction solution, and a white solid was precipitated by stirring, which was suction filtered, washed with anhydrous diethyl ether, and dried to obtain L-(+)-prolinol azonium sodium salt, namely compound 2.

[0042] (b) : Weigh a certain amount of compound 2 and dissolve it in H 2 O, the reaction was stirred in an ice bath, and the N 2 Under protection, slowly add a tetrahydrofuran solution of 1,5-difluoro-2,4-dinitrobenzene, keep warm...

Embodiment 2

[0052] Example 2 Fe 2+ - Preparation of BPDB coordination polymer

[0053] The NO donor 1,5-bis(L-prolineazonium-O 2 -)-2,4-Dinitrobenzene (BPDB) and FeCl 2 .4H 2 O was dispersed in aqueous solution at a molar ratio of 2:15, and the pH was adjusted to 5.5 with dilute NaOH solution. Then, anhydrous methanol was added under vigorous stirring to induce Fe 2+ - Formation of BPDB particles, continue stirring for a period of time until particle growth is complete. Centrifuge and wash to obtain Fe 2+ -BPDB particles. Repeat three times, the DLS characterization results of the three samples are as follows figure 2 shown. The results showed that Fe 2+ - The hydrated particle size of BPDB is greater than 1 μm, and the required nano-scale particles cannot be further prepared.

[0054] DLS characterization:

[0055] Take freshly prepared Fe 2+ - 200 μL of BPDB coordination polymer was diluted to 3 mL with distilled water, and the hydrated particle size of the liposome prepara...

Embodiment 3

[0056] Example 3 Fe 3+ / 2+ -NO donor mixed-valent coordination polymer nanoparticles (Fe 3+ / 2+ -Characterization of BPDB-NCP)

[0057] TEM and EDS determination:

[0058] Get the freshly prepared Fe of embodiment 1 poor solvent method 3+ -BPDB-NCP and Fe 3+ / 2+ -BPDB-NCP, after diluting by a certain multiple, drop it on the copper grid, and after air-drying, characterize the morphology, size (TEM) and elemental composition (EDS) of the material on a transmission electron microscope.

[0059] XPS determination:

[0060] Prepared Fe 3+ -BPDB-NCP and Fe 3+ / 2+ -After the BPDB-NCP is freeze-dried, the powder is collected, and the iron ions on the surface of the material are characterized by an X-ray photoelectron spectrometer, and the Fe is calculated by software peak division 3+ and Fe 2+ proportion.

[0061] image 3 (A) TEM, (B) EDS and (C) XPS images of each coordination-polymerized nanoparticle prepared in Example 1 of the present invention. showed that the NO donor B...

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Abstract

The invention discloses an Fe<3+ / 2+>-NO donor mixed-valence coordination polymer Fe<x+>4(BPDB)(H2O)2. In the molecular formula Fe<x+>4(BPDB)(H2O)2, Fe<x+> represents Fe<2+> and Fe<3+>, and BPDB represents a NO donor: 1,5-(L-proline azoarsen-O<2>-)-2,4-dinitrobenzene. The invention further provides a nano-particle of the Fe<3+ / 2+>-NO donor mixed-valence coordination polymer. The nano-particle has relatively high water solubility and stability and is capable of passively targeting tumors through the high permeability and retention effect (EPR effect) of solid tumor; and the nano-particle is capable of releasing NO and producing ROS under the response of high-concentration GSH and high-concentration H2O2 in a tumor microenvironment, so that the efficient, low-toxicity and synergistic treatment of the tumors is realized.

Description

technical field [0001] The invention belongs to the field of biomedical technology and nanotechnology, and specifically relates to a Fe 3+ / 2+ -NO Donor Mixed-Valence Coordination Polymers and Their Antitumor Applications. Background technique [0002] Nitric oxide (NO) is an important endogenous messenger substance and (or) effector molecule, which participates in many physiological and pathological processes in the body. In recent years, the relationship between NO and tumor occurrence, development, apoptosis, invasion and metastasis has attracted widespread attention and has become a new direction for tumor prevention and treatment. A large number of studies have shown that NO is a "double-edged sword" and has dual effects on tumors. Low concentrations of NO promote tumor development, angiogenesis and metastasis, while high concentrations of NO can inhibit tumor growth, accelerate tumor cell apoptosis, and exhibit anti-tumor effects. Therefore, the release of high conce...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G83/00A61K31/80A61P35/00
CPCA61K31/80A61P35/00C08G83/008
Inventor 丁娅黄张建胡益辉吕田
Owner CHINA PHARM UNIV
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