Composite sound-sensitive agent and preparation method thereof

A technology of composite sound and sonosensitizer, applied in chemical instruments and methods, drug combinations, manganese compounds, etc., can solve the problems of low efficiency of perfluorocarbon loading oxygen, cause side effects, and body threats, and improve tumor immunity. The effect of suppressing the microenvironment, optimizing diagnosis and treatment performance, and realizing real-time monitoring

Active Publication Date: 2021-11-05
SHANGHAI TENTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods have many disadvantages, for example, perfluorocarbons have low oxygen loading efficiency, and they are toxic, high concentration intake will pose a serious threat to the body; free hemoglobin tetramer molecules and their decomposition products can penetrate When the vascular endothelium enters the organ and tissue interstitium, it will cause side effects; due to the low concentration of hydrogen peroxide in the tumor microenvironment, the nanoparticles loaded with catalase lack the reaction substrate to generate enough oxygen, so it is difficult to achieve the desired therapeutic effect

Method used

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  • Composite sound-sensitive agent and preparation method thereof
  • Composite sound-sensitive agent and preparation method thereof
  • Composite sound-sensitive agent and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0037] The preparation method of composite sound sensitizer:

[0038] (1) Preparation of Mn by high-temperature organic phase synthesis method a W b o x initial particles. Put 20mL of benzyl ether, 1.5g of 1,2-dodecanediol and 0.35g of tungsten hexacarbonyl into a three-necked flask, stir and mix with magnetic force; under the protection of nitrogen, heat the mixed system to 120°C, add 1ml of oil acid and 1ml oleylamine, heated to 260°C, then added 0.25g manganese acetylacetonate, reacted for 30 minutes, cooled the system to room temperature, then added excess ethanol, mixed thoroughly, centrifuged, washed repeatedly with cyclohexane and ethanol , collecting the generated Mn a W b o x initial particles.

[0039] (2) Use C 18 -PEG-NH 2 to modify the synthesized Mn a W b o x Initial particle, briefly, 10mg Mn a W b o x Primary particles and 50mg C 18 -PEG-NH 2 Mixed in 4mL chloroform, sonication for 15min. Then the mixed solution was stirred at room temperature...

Embodiment 2

[0042] The in vivo biocompatibility of different groups of cells was systematically investigated separately before in vivo therapeutic evaluation. And further detect hematological indicators such as white blood cells (WBC), mean platelet volume (MPV), red blood cells (RBC), mean corpuscular hemoglobin (MCH), lymphocytes, hemoglobin (HGB), neutrophils (NEUT), and serum Biochemical indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) and urea.

Embodiment 3

[0044] (1) Test reoxygenation and related protein expression in tumor-bearing mouse models. First, by oxygen saturation-based mode (sO 2 ) photoacoustic (PA) imaging evaluated the in vivo tumor oxygenation effect under laser irradiation. Cyanobacteria (1.1×10 9 cells / ml, 100 μL) were injected into Balb / C nude mice bearing 4T1 tumors. PA imaging monitors sO 2 production;

[0045] (2) Continuous tumor oxygenation in vivo may lead to the downregulation of HIF-1α expression. The expression of HIF-1α was then monitored by Western blotting;

[0046] (3) Dynamic monitoring of HE staining and immunohistochemical staining to monitor the expression of HIF-1α and CD31.

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Abstract

The invention discloses a composite sound-sensitive agent. The composite sound-sensitive agent comprises sound-sensitive agent nanoparticles and oxygen-producing microorganisms, under the irradiation of near-infrared laser, the oxygen-producing microorganisms continuously perform photosynthesis to produce oxygen, so that an anoxic tumor area is subjected to photooxygenation, and the sound-sensitive agent is ultrasonically excited to convert the oxygen into a large amount of singlet oxygen with cytotoxicity, so that tumor cells are effectively killed and tumor tissues are effectively damaged. Immunogen cell death caused by improvement of a tumor hypoxic environment and sonodynamic therapy is realized, and synergistic therapy of sonodynamic and immune is realized. Meanwhile, the composite sound-sensitive agent can be used for magnetic resonance imaging and computed tomography contrast imaging, and real-time monitoring of the sonodynamic therapy process is achieved. The work provides good theoretical and experimental support for development of good biocompatibility and effective sonodynamic force of hybrid microorganisms, and shows important clinical transformation prospects in sonodynamic force of microbial nano medicine.

Description

technical field [0001] The invention relates to the field of ultrasonic antitumor, in particular to a composite sound sensitizer and a preparation method thereof. Background technique [0002] With the increasing morbidity and mortality, malignant tumors seriously threaten human health and life safety. In recent years, the induction of apoptosis by utilizing reactive oxygen species has been widely used in cancer therapy. Among them, sonodynamic therapy has attracted much attention as an effective strategy for cancer treatment. Ultrasound (Ultrasound, US)-mediated sonodynamic therapy is a non-invasive, high-penetrating treatment method that has great potential in the treatment of deep solid tumors. By using ultrasound to trigger the sonosensitizer, excessive reactive oxygen species are generated to trigger oxidative stress and kill cancer cells, which is the internal mechanism of sonodynamic therapy for tumors. Ideal sonodynamic therapy requires three elements: ultrasound ...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K35/748A61K47/51A61K47/60A61K39/39A61P35/00A61P35/04A61K49/08A61K51/02C01G45/00
CPCA61K41/0033A61K35/748A61K47/51A61K47/60A61K39/39A61P35/00A61P35/04A61K49/085A61K51/02C01G45/00A61K2039/55594C01P2002/80C01P2004/04A61K2300/00
Inventor 宋新然冯炜陆树婷陈雨王可屹
Owner SHANGHAI TENTH PEOPLES HOSPITAL
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