Preparation method of cancer cell membrane wrapped hollow mesporous titanium dioxide bionic medicament compound for loading autophagy inhibitor and application thereof

Abstract

The invention relates to a preparation method of cancer cell membrane wrapped hollow mesporous titanium dioxide bionic medicament compound for loading an autophagy inhibitor and an application thereof. The compound can effectively solve a pharmaceutical problem for treatment of existed cancers, and the technical scheme for solving the problem is as follows: hollow mesoporous titanium dioxide nanometer particles physically load the autophagy inhibitor in order to obtain the hollow mesoporous titanium dioxide compound for loading the autophagy inhibitor, and then the surfaces of the particles are wrapped by the cancer cell membrane through extruding, in order to form the cancer cell membrane wrapped hollow mesporous titanium dioxide bionic medicament compound for loading the autophagy inhibitor. The operation is convenient, the method is stable and reliable, and the medicament compound has the advantages of good biological compatibility, good targeting, small toxic and side effects, andthe like; in the aspects of tumour treatment, effects of targeting of cancer cell membranes, sound therapy of TiO2, and sensibilization and sound therapy of the autophagy inhibitor can be performed, and at the same time, sonodynamic treatment, medicament treatment, cancer cell membrane targeting and other multiple efficacies are provided, and interactive integrated treatment for tumour with doubleblow is provided.

Description

technical field

[0001] The invention relates to the field of medicine, in particular to a preparation method and application of a hollow mesoporous titanium dioxide biomimetic drug compound loaded with an autophagy inhibitor wrapped in a cancer cell membrane. Background technique

[0002] Surgery, radiotherapy, and chemotherapy are the three most commonly used means of tumor treatment. However, surgery can only remove tumors that are visible to the naked eye, but it is difficult to remove invisible subclinical lesions; traditional chemotherapy often has the problems of poor targeting and dose-limiting toxicity; Strong penetrating ability, and activate some sonosensitizers to generate active oxygen to exert anti-tumor effect, without damage to normal cells, so it is a safer and more efficient means of tumor treatment. Titanium dioxide (TiO 2 ) Nanoparticles have been widely used in nano drug delivery systems because of their small size and no obvious side effects. When TiO...

Examples

Embodiment 1

[0023] A method for preparing a hollow mesoporous titanium dioxide biomimetic drug complex loaded with an autophagy inhibitor wrapped in a cancer cell membrane, specifically comprising the following steps:

[0024] (1) Preparation of hollow mesoporous silica nanoparticles: Add 0.7ml of tetraethylorthosilicate to 0.3ml of water, 19ml of ethanol and 0.7ml of ammonia water, stir for 10h, centrifuge at 12000rpm for 20min to obtain a precipitate, add anhydrous Redissolve in ethanol, then centrifuge, repeat twice, the precipitate is hollow mesoporous silica nanoparticles;

[0025] (2) Preparation of hollow mesoporous SiO 2 @TiO 2Compound: Disperse the hollow mesoporous silica nanoparticles prepared in step (1) in 5ml of ethanol and 0.1ml of water, then add 0.1g of hydroxypropyl cellulose, stir for 28min to form a mixed solution; dissolve 1ml of titanium tert-butoxide In 3ml of ethanol, add dropwise to the mixed solution, reflux at 83°C for 110min, centrifuge at 12000rpm for 10min ...

Embodiment 2

[0030] A method for preparing a hollow mesoporous titanium dioxide biomimetic drug complex loaded with an autophagy inhibitor wrapped in a cancer cell membrane, specifically comprising the following steps:

[0031] (1) Preparation of hollow mesoporous silica nanoparticles: Add 0.8ml tetraethyl orthosilicate to 0.45ml water, 20ml ethanol and 0.7-0.9ml ammonia water, stir for 10-14h, centrifuge at 12000-15000rpm for 10- After 20 minutes to obtain a precipitate, add absolute ethanol to redissolve the precipitate, then centrifuge, repeat 2-3 times, the precipitate is hollow mesoporous silica nanoparticles;

[0032] (2) Preparation of hollow mesoporous SiO 2 @TiO 2 Compound: Disperse the hollow mesoporous silica nanoparticles prepared in step (1) in 10ml of ethanol and 0.2ml of water, then add 0.35g of hydroxypropyl cellulose, stir for 30min to form a mixed solution; dissolve 2ml of titanium tert-butoxide In 5ml of ethanol, add dropwise to the mixed solution, reflux at 85°C for 1...

Embodiment 3

[0038] A method for preparing a hollow mesoporous titanium dioxide biomimetic drug complex loaded with an autophagy inhibitor wrapped in a cancer cell membrane, specifically comprising the following steps:

[0039] (1) Preparation of hollow mesoporous silica nanoparticles: Add 0.8ml of tetraethylorthosilicate to 0.4ml of water, 20ml of ethanol and 0.8ml of ammonia water, stir for 13h, centrifuge at 14000rpm for 17min to obtain a precipitate, add anhydrous Redissolve in ethanol, then centrifuge, repeat twice, the precipitate is hollow mesoporous silica nanoparticles;

[0040] (2) Preparation of hollow mesoporous SiO 2 @TiO 2 Compound: Disperse the hollow mesoporous silica nanoparticles prepared in step (1) in 12ml of ethanol and 0.2ml of water, then add 0.4g of hydroxypropyl cellulose, stir for 29min to form a mixed solution; dissolve 2ml of titanium tert-butoxide In 6ml of ethanol, add dropwise to the mixed solution, reflux at 86°C for 100min, centrifuge at 14000rpm for 7min...

technical field

[0001] The invention relates to the field of medicine, in particular to a preparation method and application of a hollow mesoporous titanium dioxide biomimetic drug compound loaded with an autophagy inhibitor wrapped in a cancer cell membrane. Background technique

[0002] Surgery, radiotherapy, and chemotherapy are the three most commonly used means of tumor treatment. However, surgery can only remove tumors that are visible to the naked eye, but it is difficult to remove invisible subclinical lesions; traditional chemotherapy often has the problems of poor targeting and dose-limiting toxicity; Strong penetrating ability, and activate some sonosensitizers to generate active oxygen to exert anti-tumor effect, without damage to normal cells, so it is a safer and more efficient means of tumor treatment. Titanium dioxide (TiO 2 ) Nanoparticles have been widely used in nano drug delivery systems because of their small size and no obvious side effects. When TiO...

Examples

Embodiment 1

[0023] A method for preparing a hollow mesoporous titanium dioxide biomimetic drug complex loaded with an autophagy inhibitor wrapped in a cancer cell membrane, specifically comprising the following steps:

[0024] (1) Preparation of hollow mesoporous silica nanoparticles: Add 0.7ml of tetraethylorthosilicate to 0.3ml of water, 19ml of ethanol and 0.7ml of ammonia water, stir for 10h, centrifuge at 12000rpm for 20min to obtain a precipitate, add anhydrous Redissolve in ethanol, then centrifuge, repeat twice, the precipitate is hollow mesoporous silica nanoparticles;

[0025] (2) Preparation of hollow mesoporous SiO 2 @TiO 2Compound: Disperse the hollow mesoporous silica nanoparticles prepared in step (1) in 5ml of ethanol and 0.1ml of water, then add 0.1g of hydroxypropyl cellulose, stir for 28min to form a mixed solution; dissolve 1ml of titanium tert-butoxide In 3ml of ethanol, add dropwise to the mixed solution, reflux at 83°C for 110min, centrifuge at 12000rpm for 10min ...

Embodiment 2

[0030] A method for preparing a hollow mesoporous titanium dioxide biomimetic drug complex loaded with an autophagy inhibitor wrapped in a cancer cell membrane, specifically comprising the following steps:

[0031] (1) Preparation of hollow mesoporous silica nanoparticles: Add 0.8ml tetraethyl orthosilicate to 0.45ml water, 20ml ethanol and 0.7-0.9ml ammonia water, stir for 10-14h, centrifuge at 12000-15000rpm for 10- After 20 minutes to obtain a precipitate, add absolute ethanol to redissolve the precipitate, then centrifuge, repeat 2-3 times, the precipitate is hollow mesoporous silica nanoparticles;

[0032] (2) Preparation of hollow mesoporous SiO 2 @TiO 2 Compound: Disperse the hollow mesoporous silica nanoparticles prepared in step (1) in 10ml of ethanol and 0.2ml of water, then add 0.35g of hydroxypropyl cellulose, stir for 30min to form a mixed solution; dissolve 2ml of titanium tert-butoxide In 5ml of ethanol, add dropwise to the mixed solution, reflux at 85°C for 1...

Embodiment 3

[0038] A method for preparing a hollow mesoporous titanium dioxide biomimetic drug complex loaded with an autophagy inhibitor wrapped in a cancer cell membrane, specifically comprising the following steps:

[0039] (1) Preparation of hollow mesoporous silica nanoparticles: Add 0.8ml of tetraethylorthosilicate to 0.4ml of water, 20ml of ethanol and 0.8ml of ammonia water, stir for 13h, centrifuge at 14000rpm for 17min to obtain a precipitate, add anhydrous Redissolve in ethanol, then centrifuge, repeat twice, the precipitate is hollow mesoporous silica nanoparticles;

[0040] (2) Preparation of hollow mesoporous SiO 2 @TiO 2 Compound: Disperse the hollow mesoporous silica nanoparticles prepared in step (1) in 12ml of ethanol and 0.2ml of water, then add 0.4g of hydroxypropyl cellulose, stir for 29min to form a mixed solution; dissolve 2ml of titanium tert-butoxide In 6ml of ethanol, add dropwise to the mixed solution, reflux at 86°C for 100min, centrifuge at 14000rpm for 7min...

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