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A nanoscale coordination polymer for radiotherapy sensitization and its preparation method and application

A coordination polymer, nano-scale technology, applied in the field of biomedicine, can solve problems such as weakening ability and failure of radiotherapy, and achieve the effect of amplifying the level of oxidative stress, improving the tumor microenvironment, and stabilizing the drug state.

Active Publication Date: 2022-01-07
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This causes the hydroxyl radicals produced by RT to be consumed by GSH, which further weakens the ability of RT to generate ROS, eventually leading to the failure of radiotherapy

Method used

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  • A nanoscale coordination polymer for radiotherapy sensitization and its preparation method and application
  • A nanoscale coordination polymer for radiotherapy sensitization and its preparation method and application
  • A nanoscale coordination polymer for radiotherapy sensitization and its preparation method and application

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preparation example Construction

[0035] A preparation method of nanoscale coordination polymer for radiotherapy sensitization, Hemin, Gd 3+ and 5'-GMP are prepared by supramolecular self-assembly technology, and its supramolecular self-assembly structural formula is as follows:

[0036]

[0037] The detailed preparation process of the steps includes: dissolving Hemin and 5'-GMP into the HEPES buffer, stirring for 5-30 minutes, after mixing evenly, adding a solution containing gadolinium ions to it, stirring for 10-50 minutes, and passing through 8000 Centrifuge at ~12000rpm×10min to obtain nanoscale crude product, then wash with deionized water for 1 to 5 times, each time using 1 to 7mL of deionized water, to remove free molecular monomers; centrifuge again to obtain nanoscale pure solid; finally The nano-scale pure solid is dissolved in physiological saline for ultrasonic dispersion to obtain a particle size of 50-150nm. Nanoscale coordination polymer Hemin@Gd-NCPs.

Embodiment 1

[0038] Example 1 Preparation and Characterization of Nanoscale Radiosensitizing Drugs

[0039] Prepare GdCl first 3 ·6H 2 100 mL of O (10.0 mM, pH=7.4) solution, 100 mL of 5'-GMP (10.0 mM, pH=7.4) solution and 100 mL of Hemin (1.0 mM, pH=7.4) HEPES buffer were used for later use. Take 20mL 5'-GMP (10.0mM, pH = 7.4) in a 100mL beaker, add 20mL Hemin (1.0mM, pH = 7.4) HEPES buffer, stir magnetically for 10 minutes, then add 30mL GdCl to the system 3 ·6H 2 O (10.0 mM, pH=7.4), continue magnetic stirring for 30 minutes to form dark brown nanoparticle aggregates. Separation by centrifugation (12000rpm×10min) to obtain nanoscale crude product, and then washing with deionized water (10mL×3 times) to remove free molecular monomers, separation by centrifugation (12000rpm×10min) to obtain nanoscale pure solid product, and finally adding 10mL The normal saline was ultrasonically resuspended to obtain the nano-scale radiosensitizing drug Hemin@Gd-NCPs, the concentration of which was 2...

Embodiment 2

[0041] Example 2 Optical research and elemental characterization of nanoscale radiosensitizers

[0042] The UV-Vis absorption spectrum of Hemin@Gd-NCPs was measured by a Shimadzu UV-VIS-2450 spectrophotometer; the fluorescence spectrum was measured by a Varioskan LUX full-wavelength multifunctional microplate reader, and the same concentration of Gd-NCPs and Hemin@Gd were prepared - After the NCPs solution, scan the solution with a Varioskan LUX full-wavelength multifunctional microplate reader, and record the fluorescence value. Infrared spectra were measured by FTIR-650 Fourier transform infrared spectrometer using freeze-dried Gd-NCPs and Hemin@Gd-NCPs nanoparticles. Elemental characterization was determined by K-Alpha X-ray photoelectron spectroscopy using lyophilized Gd-NCPs and Hemin@Gd-NCPs nanoparticles.

[0043] Such as Figure 3A As shown in -D, the blank Gd-NCPs carrier has no characteristic absorption peaks, while the free Hemin and Hemin@Gd-NCPs have similar UV-...

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Abstract

The invention provides a preparation method of a nanoscale coordination polymer for radiotherapy sensitization, Hemin, Gd 3+ and 5'-GMP are prepared by supramolecular self-assembly technology. It includes the following steps: dissolve Hemin and 5'-GMP into the buffer solution, mix evenly, then add a solution containing gadolinium ions to it, after stirring, centrifuge, wash, re-centrifuge and ultrasonically disperse to obtain nano-scale coordination Polymer Hemin@Gd‑NCPs. The raw material of the present invention is cheap and easy to obtain, the preparation process is simple and easy to operate and has good controllability, and the formed nano-scale radiotherapy sensitization drug can utilize high-order ion Gd at a relatively low radiotherapy dose 3+ Effectively deposit, scatter and emit X-rays to increase the dose of local radiotherapy; improve the tumor microenvironment, amplify the level of oxidative stress in cells, generate more hydroxyl free radicals, and cooperate with radiotherapy to enhance the lethality of tumors to achieve radiotherapy enhancement. effective effect.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a nanoscale coordination polymer for radiotherapy sensitization and its preparation method and application. Background technique [0002] Radiation therapy (RT) has always been the mainstream method of clinical cancer treatment, which uses exogenous high-energy ionizing radiation (such as X-rays) to generate free radicals to damage the DNA of tumor cells. Due to its low systemic side effects and broad-spectrum efficacy, more than 50% of clinical cancer patients currently include radiotherapy in their treatment regimens. [0003] A large number of in vitro studies have confirmed that radiotherapy can achieve immune regulation by inducing immunogenic death. Specifically, X-rays can be accompanied by the release of tumor-associated antigens (TAAs) in addition to directly causing tumor cell death. The reactive oxygen species (ROS) produced by it will effectively destroy the i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/04A61K51/12A61K41/00A61P35/00A61K103/34
CPCA61K51/0472A61K51/0482A61K51/1244A61K41/0057A61P35/00
Inventor 胡一桥吴锦慧袁阿虎黄竹胜汪钰翔姚丹
Owner NANJING UNIV