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Homologous targeting tannic acid copper albumin composite nanoparticle and preparation method and anti-tumor application thereof

A composite nanoparticle, nanoparticle technology, applied in homologous targeting copper albumin tannin composite nanoparticle and its preparation, application field of tumor treatment, can solve nanoparticle tumor targeting tumor microenvironment peroxidation Insufficient hydrogen content and other problems, to achieve good tumor targeting, enhance anti-tumor effect, and increase anti-tumor effect

Active Publication Date: 2021-12-14
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The present invention discloses a method for preparing homologously targeted multifunctional nanoparticles, aiming to provide a tumor-targeted multifunctional nanoparticle with simple preparation, controllable size and stable properties. Functional nanoparticles to solve the problem of nanoparticle tumor targeting and insufficient hydrogen peroxide content in the tumor microenvironment

Method used

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  • Homologous targeting tannic acid copper albumin composite nanoparticle and preparation method and anti-tumor application thereof
  • Homologous targeting tannic acid copper albumin composite nanoparticle and preparation method and anti-tumor application thereof
  • Homologous targeting tannic acid copper albumin composite nanoparticle and preparation method and anti-tumor application thereof

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Effect test

Embodiment 1

[0046] The extraction of embodiment 1 cancer cell membrane

[0047] Collect the MDA-MB-231 breast cancer cells in a 10cm culture dish, centrifuge at 1000rpm for 4min, collect the pelleted cells, then add 1mL neutral lysate (containing protease inhibitors) to the pelleted cells, 1~1.5mL / tube, place in an ice bath 20min. Then it was further ultrasonicated for 30s in ice bath protection (power 20% super 2s stop 2s). The sonicated cell suspension was centrifuged at 3200 g for 5 min, and the supernatant was taken. Finally, the above supernatant was further centrifuged at 4° C. and 20,000 g for 20 min under the condition of high-speed centrifugation, and the supernatant was collected to obtain a cell membrane suspension.

Embodiment 2

[0048] Example 2 Preparation of homologous targeting copper tannate human serum albumin composite nanoparticles

[0049] Weigh 20 mg of human serum albumin, dissolve 5 mg of glucose oxidase in 2 mL of deionized water, and mix with human serum albumin evenly. Add 100 μL of chloroform, and under the protection of an ice bath, perform intermittent ultrasonication for 5 minutes to remove the organic solvent and obtain a nanocomposite system; add 200 μL of 0.1 M sodium carbonate aqueous solution, and ultrasonically clean the solution for 5 minutes to obtain a transparent and clear nanoparticle aqueous solution. Add 10 μL of tannic acid (40 mg / mL) to 2 mL of the above nanoparticle solution, followed by 200 μL of CuCl 2 .2H 2 O (6.3mg / mL), continue stirring for 30min to obtain Cu-TA nanoparticles. Finally, the prepared cell membrane solution was added and passed through a 220nm filter 10 times by a film extrusion method to obtain the homologously targeted copper tannate human serum...

Embodiment 3

[0050] Example 3 In different concentrations of hydrogen peroxide, the detection of composite nanoparticles producing ROS in aqueous solution

[0051] Under dark light conditions, 4 μL of 10 μM 2′,7′-dichlorofluorescein diacetate was added to 2 mL of the composite nanoparticles obtained in Example 2 containing different hydrogen peroxide concentrations (0 mM, 10 mM, 50 mM, 100 mM) (DCFH-DA) fluorescent probe, after diluting a certain number of times, detect the fluorescence intensity of active oxygen with a multifunctional microplate reader, and obtain the active oxygen concentration after the reaction. The results are as follows: image 3 As shown, the reactive oxygen species produced by the nanoparticles are positively correlated with the concentration of hydrogen peroxide, and the reactive oxygen species increase with the increase of hydrogen peroxide, which can achieve a highly efficient Fenton-like reaction effect.

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Abstract

The invention discloses a homologous targeting tannic acid copper albumin composite nanoparticle and preparation method and anti-tumor application thereof. The targeted tannic acid copper albumin composite nanoparticle comprises a nano-particle inner core, a tannic acid and copper complex wrapped outside the nano-particle inner core and a cancer cell membrane with targeting ability, and the nanoparticle inner core is composed of albumin and glucose oxidase adsorbed on the albumin. The preparation method mainly adopts an ultrasonic mode, and is simple to operate, good in repeatability and controllable in size. The nanoparticle has homologous targeting property, the tannic acid copper complex and hydrogen peroxide can be subjected to Fenton-like reaction, and generated hydroxyl free radicals can effectively kill cancer cells. In addition, under the combined action of glucose oxidase, the content of hydrogen peroxide in a cancer cell microenvironment is increased, and the effect of the Fenton-like reaction is further improved; and the tannic acid copper complex can generate ROS under the excitation of ultrasonic waves, and has the effect of cooperatively killing tumor cells.

Description

technical field [0001] The invention belongs to the field of antitumor drugs, and in particular relates to a homologously targeted tannic acid copper albumin composite nanoparticle, a preparation method thereof, and an application in tumor treatment. Background technique [0002] The incidence of malignant tumors is increasing year by year, seriously threatening human life and health, and is the number one cause of death before the age of 70. Traditional tumor treatment methods mainly rely on surgical resection, supplemented by chemotherapy and radiotherapy. However, malignant tumors often grow infiltrating. Surgery can only remove solid tumors with clear borders. It is difficult to remove all infiltrating tumors accurately. Chemotherapy drugs usually do not target the tumor well, and radiotherapy is based on the whole body. Treatment means, this non-specific treatment method can inhibit the growth of tumor tissue and cause irreversible damage to normal tissue, but it still...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/51A61K47/46A61K47/42A61P35/00B82Y5/00B82Y30/00B82Y40/00C12N5/09A61K38/44
CPCA61K41/0033A61K9/5176A61K9/5169A61K9/5192A61K38/443C12Y101/03004A61P35/00B82Y5/00B82Y30/00B82Y40/00C12N5/0693C12N2509/10C12N2509/00A61K2300/00
Inventor 黄来强陈华清代小勇李婧林高扬孙芬王丽君吴佳敏
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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