Application of cancer cell membrane bionic nano-reactor AGZ@CM in preparation of anti-cancer drugs

A technology of bionic nanometer and cancer cell membrane, which is applied in the field of biomedicine, can solve the problems of loss of catalytic activity, etc., and achieve the effect of easy acquisition, simple preparation method and simple principle

Inactive Publication Date: 2020-08-07
SOUTHEAST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the potential safety issues of nanocarriers due to leakage and aggregation, low loading and loss of catalytic activity in protein delivery, all urgently need to be addressed.

Method used

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  • Application of cancer cell membrane bionic nano-reactor AGZ@CM in preparation of anti-cancer drugs
  • Application of cancer cell membrane bionic nano-reactor AGZ@CM in preparation of anti-cancer drugs
  • Application of cancer cell membrane bionic nano-reactor AGZ@CM in preparation of anti-cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Synthesis of ZIF-8 NPs

[0041] 2-mIM (160 mmol L -1 , 50 mL) and zinc acetate (40 mmol L -1 , 50 mL) were dissolved in methanol solution. Zinc acetate was added to 2-mIM with stirring at room temperature. After stirring for 12 h, the product was collected and washed 3 times with methanol. The precipitate was dried under vacuum overnight.

[0042] figure 2 A shows the SEM image of the synthesized ZIF-8 NPs, obtained from figure 2 As can be seen in A, ZIF-8 exhibits a uniform dodecahedral morphology with an average diameter of 250 nm. It indicated that ZIF-8 NPs were successfully synthesized.

Embodiment 2

[0043] Example 2: Synthesis of AZ, GZ and AGZ

[0044] First, 1 mg GOx was dissolved in 1 mL deionized water, and then 2 mg PVP (MW: 8000) was added. After stirring for 30 s, another 1 mg of Cys was introduced under stirring, and AQ4N was added to the mixed solution. Finally, 2 mL of mIM (160 mmolL -1 ) and 2 mL of zinc acetate solution (40 mmol L -1 ) and aged at room temperature for 4 h. Centrifuge, wash with water, and freeze-dry to obtain AGZ nanoparticles. AZ and GZ were synthesized in the same way, except that GOx and AQ4N were not added, respectively.

[0045] like figure 2 SEM of B and figure 2 As shown in the TEM of C, the shape and size of the GOx enzyme and prodrug AQ4N were not significantly changed after encapsulation into ZIF-8 nanoparticles, indicating that the encapsulation did not destroy the structure of ZIF-8.

Embodiment 3

[0046] Example 3: CM coated ZIF-8, AZ, GZ and AGZ nanoparticles

[0047] First, human hepatoma cell (HepG2) membranes were obtained using a membrane protein extraction kit. Briefly, cells were harvested with a cell spatula and collected by centrifugation with PBS. Thereafter, the collected cells were dispersed in membrane protein extraction buffer and PMSF. Then, the cells were quickly frozen and thawed three times in liquid nitrogen and at room temperature. The suspension was centrifuged at 4°C (700 g, 10 min) and the supernatant was further centrifuged at 4°C (14000 g, 30 min). Second, HepG2 cell membranes were mixed with nanoparticles in equal volumes and sonicated for 30 s to make the mixture homogeneous. The mixture was then continuously extruded 11 times through a 400 nm polycarbonate porous membrane using an Avanti micro-extruder (Avanti Polar Lipids). Excess membranes were discarded by centrifugation, and the final membrane-encapsulated nanoreactors were dissolved ...

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Abstract

The invention discloses application of a cancer cell membrane bionic nano reactor AGZ@CM in preparation of anti-cancer drugs. The efficient synergistic treatment method for tumors comprises the following step: performing one-pot synthesis on a nano reactor AQ4N / GOx@ZIF-8 by virtue of an amino-acid-induced bionic method to realize rapid encapsulation and ultrahigh loading efficiency of glucose oxidase and keep the natural biological activity of the glucose oxidase. The bionic nano-reactor AGZ@CM prepared by coating the surface of AGZ with a targeting cell membrane coating has homotype targetingand immune escape functions; after a cascade reaction in which the ZIF-8 carrier is decomposed in the presence of acid to release a drug, GOx mediated glucose oxidation is performed and a prodrug AQ4N is activated, synergistic treatment of hunger therapy and chemotherapy is realized. In-vitro and in-vivo research results show that the synergistic strategy of hunger therapy and chemotherapy can improve the treatment effect, and the cell membrane coating endows the nano-reactor with strong targeting ability; the bionic intelligent cascade reaction nanoreactor disclosed by the invention has theclinical potential of treating tumors.

Description

technical field [0001] The invention relates to the technical field of biomedicine, and specifically relates to the application of the cancer cell membrane biomimetic nano-reactor AGZ@CM in the preparation of anticancer drugs. Background technique [0002] Compared with normal tissue cells, tumor cells require a lot of nutrients and energy to maintain their survival and growth due to the disorder of metabolic pathways. Glucose is the main energy source for tumor proliferation and metabolism. Once the glucose supply is cut off, tumor growth will be preferentially inhibited. Therefore, starvation therapy, which inhibits tumor cell proliferation by cutting off nutrient supply, has attracted great interest. Glucose oxidase (GOx) consumes O 2 and glucose, which catalyze the production of hydrogen peroxide (H 2 o 2 ) causes oxidative damage to the cells and produces gluconic acid to lower the pH. However, a single starvation therapy cannot achieve a satisfactory therapeutic ef...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/22A61K47/46A61K38/44A61K31/136A61P35/00
CPCA61K9/5115A61K9/5176A61K31/136A61K38/443A61P35/00C12Y101/03004A61K2300/00
Inventor 刘松琴吴亚锋邵凤英
Owner SOUTHEAST UNIV
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