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Nanoparticles cooperating with NO gas treatment and enhancing sonodynamic therapy effect as well as preparation method and application of nanoparticles

A technology of sonodynamic therapy and nanoparticles, applied in the field of biomedicine, can solve problems such as complex principles and achieve the effect of enhancing sonodynamic therapy

Pending Publication Date: 2022-01-18
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The actual principle of SDT action is more complicated. Unlike the photodynamic effect caused by PDT, which is a single activation of photosensitizer by light radiation through energy and electron transfer processes to induce reactive oxygen species (ROS), SDT may also include cavitation cavitation effects, Mechanisms such as thermal effect and direct induction of apoptosis

Method used

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  • Nanoparticles cooperating with NO gas treatment and enhancing sonodynamic therapy effect as well as preparation method and application of nanoparticles
  • Nanoparticles cooperating with NO gas treatment and enhancing sonodynamic therapy effect as well as preparation method and application of nanoparticles
  • Nanoparticles cooperating with NO gas treatment and enhancing sonodynamic therapy effect as well as preparation method and application of nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Weigh 2.0 g of cetyltrimethylammonium chloride (CTAC) and 0.1 g of triethanolamine (TEA) into the same 50 mL round bottom flask, mix them, add 20 mL of ultrapure water to it, and place the flask Stir the reaction in an oil bath at 95°C for 1 h. After the reaction was over, 1.5 mL of tetraethoxysilane (TEOS) was added dropwise to the reaction solution using a 1 mL syringe, and then the reaction was continued to stir for 1 h in an oil bath at 95 °C. Subsequently, after the reaction liquid was cooled to room temperature, it was centrifuged at 12,000 rpm for 30 min, and the supernatant was removed, and the centrifuged precipitate was washed three times with absolute ethanol. The washed precipitate was added to 20 mL sodium chloride-methanol mixture (1 g NaCl dissolved in 100 mL methanol), stirred at room temperature for 4 h, and then the reaction solution was centrifuged at 10,000 rpm for 10 min, and the supernatant was removed. The precipitate after centrifugation was was...

Embodiment 2

[0040] Weigh 100 mg of MSN-OH into a 50 mL round bottom flask, measure 200 μL of 3-aminopropyltriethoxysilane (APTES) into the same flask, then add 20 mL of absolute ethanol to it, and the flask Place it in an oil bath at 60°C for 4 h under magnetic stirring, then centrifuge the reaction solution at 10,000 rpm for 10 min, remove the supernatant, and wash the centrifuged precipitate three times with absolute ethanol and ultrapure water , and then freeze-dry the washed precipitate to obtain MSN-NH 2 (MSN).

Embodiment 3

[0042] Weigh 10 mg of 1-ethyl-3-(3-dimethylamino)carbodiimide (EDC) and 8 mg of N-hydroxysuccinimide (NHS) into the same 5 mL round bottom flask, mix After adding 2 mL of ultrapure water and mixing for 15 min, 0.2 nmol carboxy-modified nucleic acid aptamer E-APt targeting EGFR (purchased from Sangon Bioengineering (Shanghai) Co., Ltd., its specific sequence See literature Zhu F, Xu L, Li X, Li Z, Wang J, Chen H, et al. Co-delivery of gefitinib and hematoporphyrin by aptamer-modified fluorinated dendrimer for hypoxia alleviation and enhanced synergistic chemo-photodynamic therapy of NSCLC. Eur J Pharm Sci 2021;167:106004.), the reaction was stirred at room temperature for 3 h to activate the carboxyl group. Then add 10 mg MSN-NH to the reaction solution 2 , stirring the reaction at room temperature for 24 h, so that the nucleic acid aptamer E-APt and MSN-NH 2 covalently linked. Then the reaction solution was centrifuged at 12000 rpm for 10 min, the supernatant was removed, t...

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Abstract

The invention discloses nanoparticles cooperating with NO gas treatment and enhancing sonodynamic therapy as well as a preparation method and application of the nanoparticles. The nanoparticles are prepared by taking aptamer modified mesoporous silica as a carrier, then loading L-arginine and hematoporphyrin and performing self-assembly. After being modified by an aptamer, the nanoparticles can recognize tumor cells with mutated epidermal growth receptors in a targeted manner; the hematoporphyrin is used as a sound-sensitive agent, generates active oxygen after being subjected to ultrasonic treatment, generates cytotoxicity and can exert the sonodynamic treatment effect of the hematoporphyrin; and the L-arginine is used as an NO donor, NO gas can be generated after cell metabolism, the NO gas and active oxygen further react to generate nitrite ONOO<-> with higher toxicity, and therefore, lung cancer cells are selectively killed. According to the nanoparticles, the aptamer modified carrier is used as a delivery system, NO gas treatment and sonodynamic treatment are combined, the tumor cells are recognized in a targeted mode, and tumor cell proliferation is inhibited to the maximum extent.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a nanoparticle that cooperates with NO gas therapy and enhances the effect of sonodynamic therapy, and a preparation method and application thereof. Background technique [0002] Lung cancer is one of the most common cancers in the world, seriously endangering human public health. Lung cancer is divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) from histological point of view, and 85% of lung cancers belong to NSCLC. Compared with SCLC, NSCLC has a wider range and more complicated etiology, and most NSCLCs are discovered at an advanced stage. Systemic therapies such as radiotherapy and chemotherapy are widely used in the treatment of lung cancer. However, radiotherapy and chemotherapy have disadvantages such as poor tumor selectivity and high toxicity and side effects, which stimulate the development of other treatment methods. [...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K41/00A61K47/54A61P11/00A61P35/00B82Y5/00A61K31/198
CPCA61K47/6949A61K47/6929A61K47/549A61K31/198A61K41/0033A61P35/00A61P11/00B82Y5/00A61K2300/00Y02A50/30
Inventor 高瑜张培霞王俊朱芳银张盈璐陈海军
Owner FUZHOU UNIV
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