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Nanocomposite with low skin phototoxicity for sonodynamic therapy as well as preparation method and application of nanocomposite

A nanocomposite and sonodynamic therapy technology, applied in the field of biomedicine, can solve the problems of patent publications that have not yet been found, and achieve the effects of reducing defense capabilities, improving sonodynamic efficiency, and increasing uptake

Pending Publication Date: 2022-07-29
TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Through searching, no patent publication related to t

Method used

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  • Nanocomposite with low skin phototoxicity for sonodynamic therapy as well as preparation method and application of nanocomposite
  • Nanocomposite with low skin phototoxicity for sonodynamic therapy as well as preparation method and application of nanocomposite
  • Nanocomposite with low skin phototoxicity for sonodynamic therapy as well as preparation method and application of nanocomposite

Examples

Experimental program
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Example Embodiment

[0055] Preferably, the preparation method of the imidazole derivative containing disulfide bond comprises the following steps:

[0056] The structure (II) and N,N'-carbonyldiimidazole (III) of the two-terminal carboxyl group of the disulfide bond were dissolved in the organic solvent three, and the reaction was stirred at 30 ° C for 4 hours; -5 times, then add ultrapure water to wash 2-5 times, and dry to obtain the organic monomer (I) containing disulfide bond double-end imidazole;

[0057] Reaction formula:

[0058]

[0059] Wherein, n=2-4;

[0060] The organic solvent three is N,N-dimethylformamide, tetrahydrofuran or dichloromethane.

[0061] Preferably, the sonosensitizer is titanium dioxide, and its preparation steps are as follows:

[0062] ① After mixing absolute ethanol, oleic acid and tetrabutyl titanate, stir at room temperature for 5 minutes; wherein, the ratio of absolute ethanol: oleic acid: tetrabutyl titanate, mL:mL:g is 15:5:0.57 ;

[0063] ② Transfer ...

Example Embodiment

[0078] Example 1

[0079] The preparation method of the organic monomer (I-a) containing disulfide bond double-end imidazole, comprises the steps:

[0080] Accurately weigh 0.3778g (1.585mmol) (II-a) of 4,4'-dithiodibutyric acid and 0.6333g (3.906mmol) (III) of N,N'-carbonyldiimidazole (CDI) into a 100mL circle. In the bottom flask, the system was sealed, evacuated and filled with nitrogen, 40 mL of anhydrous dichloromethane (DCM) was added using a syringe, vacuumed again, filled with nitrogen, and the reaction was stirred at 30° C. for 4 hours. After the reaction, use a rotary evaporator to remove dichloromethane and CO produced by the reaction 2 , then add 40mL of dichloromethane to dissolve, after complete dissolution, transfer the solution to a separatory funnel, and add 40mL of 0.1M sodium carbonate solution to it to wash, repeat the washing three times, add 40mL of ultrapure water to wash three times again, The organic phase was collected and an appropriate amount of a...

Example Embodiment

[0087] Example 2

[0088] A preparation method of sonosensitizer titanium dioxide, comprising the steps:

[0089] 15 mL of absolute ethanol, 5 mL of oleic acid and 0.57 g of tetrabutyl titanate were respectively added to a dry 50 mL conical flask and stirred at room temperature for 5 min. Then the mixture was transferred to a 50 mL autoclave and placed in an oil bath, and reacted at 180° C. for 4 h. After 4 hours, the autoclave was taken out and cooled in a ventilated place for 2 hours. The dark yellow liquid was placed on average in 4 EP tubes and centrifuged (10000r, 10min), and then the precipitate was washed twice with absolute ethanol to remove excess oleic acid to obtain oil. Acid-modified titanium dioxide (OA-TiO 2 ). Finally, the dark yellow precipitate was dispersed in 6 mL of tetrahydrofuran.

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Abstract

The invention discloses a nano compound for sonodynamic therapy with low skin phototoxicity, which is characterized in that disulfide bond-containing imidazole derivatives are used as organic ligands, metal ions are used as chelating metals, the disulfide bond-containing imidazole derivatives and the chelating metals form a nano metal organic framework, a sound-sensitive agent is entrapped on the nano metal organic framework, poloxamer is further coated on the outer layer of the metal organic framework, and the nano compound is prepared. The invention also discloses a preparation method. The nano-composite can reduce the phototoxicity of the sonosensitizer in normal tissues and organs, can realize intracellular rapid release through huge concentration difference of GSH inside and outside tumor cells, and has a molecular targeting effect and a sonodynamic curative effect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to a nanocomposite for sonodynamic therapy with low skin phototoxicity and a preparation method and application thereof. Background technique [0002] Skin exposure to sunlight and photoreactive xenobiotics may cause abnormal skin reactions, resulting in phototoxicity. Phototoxicity is an acute light-induced reaction that occurs when photoreactive chemicals are activated by sunlight and converted into substances that are toxic to skin cells. The ultraviolet region is the main absorption region for phototoxicity, and photoactive molecules absorb energy to generate reactive oxygen species to induce phototoxicity. Most sonosensitizers are also photosensitizers, so their phototoxicity and skin sensitivity after cancer treatment have side effects on the human body. The sonosensitizer TiO 2 Toxic reactive oxygen species are produced under UV light irradiation. Ultraviolet light can...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/69A61K9/51A61K47/10A61P35/00C01G23/053C07D233/56C08G83/00
CPCA61K41/0033A61K47/6949A61K9/5146A61P35/00C07D233/56C01G23/053C08G83/008Y02A50/30
Inventor 孟璇赵宁戴玉杰王征赵燕军王林景文杰
Owner TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY
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