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Intelligent nanoparticles based on double-selenium-bond polymer, and preparation method and application of intelligent nanoparticle

A technology of polymers and nanoparticles, applied in the direction of medical preparations, drug combinations, and pharmaceutical formulations of non-active ingredients, which can solve problems such as unusable and inconsistent clinical applications

Pending Publication Date: 2020-01-07
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, a dose of 5 Gy to 10 Gy is required, which is inconsistent with clinical application and cannot be used for the clinical requirement of 2 Gy irradiation

Method used

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  • Intelligent nanoparticles based on double-selenium-bond polymer, and preparation method and application of intelligent nanoparticle
  • Intelligent nanoparticles based on double-selenium-bond polymer, and preparation method and application of intelligent nanoparticle
  • Intelligent nanoparticles based on double-selenium-bond polymer, and preparation method and application of intelligent nanoparticle

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Experimental program
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Effect test

Embodiment 1

[0046] Add 1.0 g (12.6 mmol) of sodium borohydride dissolved in 10 ml of deionized water slowly and dropwise into 15 mL of deionized water containing 1.0 g (26.4 mmol) of selenium powder under stirring at room temperature, and react for 10 minutes , followed by adding 1.0 g (26.4 mmol) of selenium powder, stirring for 15 minutes, then adding 6.33 g (25.2 mmol) of bromidecanol dissolved in 25 ml of THF, and reacting in an oil bath at 50°C for 24 hours; The residue of the reaction was extracted three times with dichloromethane, dried with anhydrous sodium sulfate for 24 hours, filtered to remove sodium sulfate, and purified by column chromatography (volume ratio of 4:1 dichloromethane / ethyl acetate as eluent) The product, a yellow powder (yield 61%), is a small molecular monomer of di-selenium. 1 H-NMR (300 MHz, CDCl 3 , δ)(ppm): 3.63 (4H, t, HOC H 2 ), 2.90 (4H, t, SeSeC H 2 ) 1.72-1.28(36H, m, HOCH 2 (C H 2 ) 9 CH 2 SeSe); LC-MS: theoretical molecular weight 500.53, ...

Embodiment 2

[0053] Add 1.0 mg DOX·HCl, 0.1 ml TEA and 10 mg Se-polymer into 2 mL DMF, stir for 2 h, then add 10 mL deionized water dropwise within 5 hours under stirring, and dialyze with deionized water after the addition (MWCO 3500 Da) for 24 hours, and then centrifuged with an ultrafiltration centrifuge tube (MWCO 10000 Da) to obtain drug-loaded nanoparticles (D-NPs) containing diselenium bonds. In order to measure DOX loading (DLC) and drug loading efficiency (DLE), D-NPs were dried by freeze dryer and dissolved in DMSO, and measured by UV-vis spectrometer. It was found that the DOX loading of the above D-NPs (DLC ) and drug loading efficiency (DLE) values ​​were calculated to be 8.69% and 41.78%, respectively.

[0054] Transmission electron microscopy (TEM) characterization analysis such as figure 2 Shown in A, the successful fabrication of the designed DOX-loaded dual-Se nanoparticles (D-NPs) was demonstrated. According to the dynamic light scattering (DLS) measurement, D-NPs hav...

Embodiment 3

[0060] Nile red (NR) was loaded as a model compound to study drug release in vitro because of its 2 o 2 And high stability under X-ray conditions. image 3 In order to release NR from Nile Red-loaded nanoparticles (NR-NPs) in vitro under different conditions, the data are expressed as mean ± standard deviation, n=3, specifically the PBS control group, simple X-ray irradiation group (2Gy, 5Gy and 10Gy), single H 2 o 2 Treatment group (100 μM), X-ray and H 2 o 2 Synergistic group (2Gy X-ray, 5Gy X-ray, 10Gy X-ray use 100μM H 2 o 2 co-treatment); the X-ray exposure dose used here is comparable in clinical practice, set H 2 o 2 The concentration (100 μM) matched the ROS level in the real tumor microenvironment; a fluorescence spectrophotometer, excited at 543 nm, was performed in the wavelength range of 500 to 700 nm to determine the content of NR. Interestingly, in all three groups irradiated with X-rays alone at different doses, the drug release behavior was not signifi...

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Abstract

The invention discloses intelligent nanoparticles based on a double-selenium-bond polymer, and a preparation method and an application of the intelligent nanoparticles. Simple amphiphilic nanoparticles (Se-NPs) containing diselenide are designed. The Se-NPs can intelligently release a medicine in the nanoparticles under X rays. An in-vivo experiment on a 4T1 tumor-bearing mouse shows that due to the EPR effect, a loaded drug can be enriched at a tumor site, the drug can be triggered to be rapidly released into tumor cells from the Se-NPs under the low X-ray dosage (equivalent to the conventional dosage adopted in clinical single radiotherapy) of 2Gy, the obvious combined anti-tumor effect is achieved, and the side effect is small. Besides, the prepared Se-NPs not only have no toxicity, butalso can reduce the adverse cytotoxicity of the antitumor drug to normal cells, and it is indicated that the Se-NPs have quite good biocompatibility. An effective means is provided for enhancing thecancer treatment effect, and extremely low side effects is achieved.

Description

technical field [0001] The invention belongs to the technology of smart drugs, and in particular relates to smart nanoparticles based on double-selenium bond polymers, a preparation method and application thereof. Background technique [0002] Radiation therapy (RT) is one of the main methods of treating cancer. More than half of cancer patients are treated with RT alone or in combination with other radiotherapy or surgery in the current clinical treatment. High-energy radiation, such as X-rays, is usually used for RT, mainly by interacting with the cytoplasm and nucleus of tumor cells in the irradiated area to destroy tumor tissues, such as generating reactive oxygen species (ROS) accumulation and DNA strand breaks, while inevitably affecting normal cells. Cell damage. However, certain tumor microenvironments confer radiation resistance on tumor cells, thereby inhibiting the application potential of RT. Although the combined application of RT and anticancer drugs exhibit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G18/32C08G18/75C08G18/48C08G18/66A61K47/34A61P35/00
CPCA61K47/34A61P35/00C08G18/3897C08G18/4833C08G18/6666C08G18/755
Inventor 杨再兴张连学李友云杨莹段广新徐加英周如鸿
Owner SUZHOU UNIV
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