Pharmaceutical composition of cytomembrane bionic titanium dioxide nanoparticles

A technology of titanium dioxide and drug complex, applied in the field of biomedicine, can solve the problems of immune escape, tumor cell apoptosis, etc., and achieve the effects of low production cost, good biocompatibility, and huge economic and social benefits.

Active Publication Date: 2019-04-19
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In view of the above situation, in order to solve the defects of the prior art, the purpose of the present invention is to provide a pharmaceutical composition of biomimetic titanium dioxide nanoparticles of cell membrane, which can effectively solve the problem of immune escape and long circulation, and promote the development of tumor cells by enhancing sound therapy combined with NO chemotherapy. The problem of apoptosis

Method used

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  • Pharmaceutical composition of cytomembrane bionic titanium dioxide nanoparticles

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] 1) Add 0.8mL tetraethyl orthosilicate (TEOS) to a flask filled with 0.4mL ultrapure water, 20mL absolute ethanol and 0.8mL ammonia water, stir vigorously for 12h, centrifuge at 12000rpm for 15min, wash with absolute ethanol to neutral to obtain silica nanoparticles (SiO 2 );

[0018] 2) Disperse the silica nanoparticles prepared in step 1) in a solution made of 15 mL of absolute ethanol and 0.1 mL of ultrapure water, then add 0.1 g of hydroxypropyl cellulose dissolved in 5 mL of absolute ethanol and stir for 30 min , to form a mixed solution, dissolve 1mL titanium tert-butoxide in 5mL absolute ethanol, slowly add it dropwise into the mixed solution, reflux at 85°C for 100min, centrifuge at 12000rpm for 15min, wash with absolute ethanol three times to obtain SiO 2 @TiO 2 Complex;

[0019] 3) SiO prepared in step 2) 2 @TiO 2 The complex was dispersed in 20mL ultrapure water, added 0.2g PVPk30, stirred for 12h, centrifuged at 12000rpm for 8min to obtain a precipitate,...

Embodiment 2

[0026] 1) Add 0.6mL tetraethyl orthosilicate (TEOS) into a flask filled with 0.3mL ultrapure water, 15mL absolute ethanol and 0.6mL ammonia water, stir vigorously for 10h, centrifuge at 10000rpm for 10min, wash with absolute ethanol to neutral to obtain silica nanoparticles (SiO 2 );

[0027] 2) SiO obtained in step 1) 2 Disperse in a solution made of 10mL of absolute ethanol and 0.05mL of ultrapure water, then add 0.05g of hydroxypropyl cellulose dissolved in 2.5mL of absolute ethanol and stir for 30min to make a mixed solution, and 0.5mL of titanium tert-butoxide After dissolving in 2.5mL of absolute ethanol, slowly add it dropwise into the mixed solution, reflux at 80°C for 90min, centrifuge at 10000rpm for 10min, and wash twice with absolute ethanol to obtain SiO 2 @TiO 2 Complex;

[0028] 3) SiO prepared in step 2) 2 @TiO 2 The complex was dispersed in 15mL ultrapure water, added 0.1g PVPk30, stirred for 10h, centrifuged at 10000rpm for 5min to obtain a precipitate,...

Embodiment 3

[0035] 1) Add 1 mL of tetraethyl orthosilicate (TEOS) to a flask containing 0.5 mL of ultrapure water, 25 mL of absolute ethanol and 1 mL of ammonia water, stir vigorously for 14 hours, centrifuge at 15,000 rpm for 20 minutes, and wash with absolute ethanol until medium properties, to obtain silica nanoparticles (SiO 2 );

[0036] 2) SiO obtained in step 1) 2 Disperse in a solution made of 20mL of absolute ethanol and 0.15mL of ultrapure water, then add 0.15g of hydroxypropyl cellulose dissolved in 7.5mL of absolute ethanol and stir for 30min to make a mixed solution, and 1.5mL of titanium tert-butoxide After dissolving in 7.5mL of absolute ethanol, slowly add it dropwise to the mixed solution, reflux at 90°C for 110min, centrifuge at 15000rpm for 20min, wash 4 times with absolute ethanol to obtain SiO 2 @TiO 2 Complex;

[0037] 3) SiO prepared in step 2) 2 @TiO 2 The complex was dispersed in 25mL ultrapure water, added 0.3g PVPk30, stirred for 14h, centrifuged at 15000r...

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Abstract

The invention relates to a pharmaceutical composition of cytomembrane bionic titanium dioxide nanoparticles. The pharmaceutical composition can effectively achieve immune escape and long circulation,and promote apoptosis of tumor cells through enhanced acoustic therapy combined with NO chemotherapy. According to the technical scheme, the surfaces of hollow mesoporous titanium dioxide nanoparticles are covalently modified by hemoglobin through an amidation reaction, then physically loaded with an NO donor type chemotherapy drug RRx-001, and finally coextruded with cytomembrane vesicle obtainedthrough pyrolysis treatment of a hypotonic lysis solution and homogenate with cells, and the pharmaceutical composition of the cytomembrane bionic titanium dioxide nanoparticles is obtained. The pharmaceutical composition of the cytomembrane bionic titanium dioxide nanoparticles has the advantages that a preparation method is stable and reliable, the production cost is low, the prepared pharmaceutical composition of the cytomembrane bionic titanium dioxide nanoparticles can play a role of the enhanced acoustic therapy combined with NO chemotherapy in the preparation of antitumor drugs, enhances the antitumor effect, has immune escape and long circulation and other functions, is good in biocompatibility, and is innovation of tumor therapy drugs.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a pharmaceutical composition of cell membrane bionic titanium dioxide nanoparticles. Background technique [0002] Sonodynamic therapy (Sonodynamic Therapy, SDT) is a method in which sonosensitizers are excited by ultrasound to generate reactive oxygen species (ROS), thereby exerting anti-tumor effects. Hollow mesoporous titania nanoparticles (TiO2) have the advantages of good biocompatibility, high chemical stability, and large specific surface area as a sonosensitizer. However, sound therapy is oxygen-dependent, and the lack of oxygen in the tumor site seriously weakens the effect of SDT. Hemoglobin (Hb) is an important protein that transports oxygen in red blood cells, and has reversible oxygen binding and dissociation capabilities; at the same time, deoxy Hb also has nitrite reductase activity, which can reduce nitrite to NO. The chemotherapeutic drug RRx-001, as a new anticancer...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/397A61K47/46A61K47/64A61P35/00
CPCA61K31/397A61K41/0033A61K47/46A61K47/6445A61P35/00A61K2300/00
Inventor 冯倩华张振中李玉真郝雨桐王宁张红岭
Owner ZHENGZHOU UNIV
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