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Amorphous calcium carbonate composite nano-medicine with effect of inducing ferroptosis of tumor cells and preparation method of amorphous calcium carbonate composite nano-medicine

A technology of tumor cells and composite nanoparticles, which is applied in the field of amorphous calcium carbonate composite nanomedicine and its preparation, can solve the problems of cancer cell gene mutation, cell apoptosis pathway blocking, etc., to reduce rejection, increase tumor treatment effect, Enhances the effect of ferroptosis

Active Publication Date: 2020-06-05
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Traditional tumor treatment methods (such as chemotherapy and radiotherapy) are usually based on the induction of tumor cell apoptosis, but cancer cells are prone to gene mutations, resulting in blocked apoptosis pathways

Method used

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  • Amorphous calcium carbonate composite nano-medicine with effect of inducing ferroptosis of tumor cells and preparation method of amorphous calcium carbonate composite nano-medicine
  • Amorphous calcium carbonate composite nano-medicine with effect of inducing ferroptosis of tumor cells and preparation method of amorphous calcium carbonate composite nano-medicine
  • Amorphous calcium carbonate composite nano-medicine with effect of inducing ferroptosis of tumor cells and preparation method of amorphous calcium carbonate composite nano-medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Preparation of amorphous calcium carbonate composite nanomedicine with the effect of inducing ferroptosis in tumor cells

[0043] (1) Preparation of alkynylated second-generation polyamide-amine dendrimer (PAMAM-FA) grafted with folic acid

[0044] Add 60mg of folic acid, 80mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 47mg of N-hydroxysuccinimide into 25mL of N,N-dimethylformamide and activate for 0.5h Then add 100 mg of alkynylated second-generation polyamide-amine dendrimers, stir and react at room temperature for 24 hours, and then dialyze with a dialysis bag with a molecular weight of 1000 Da to obtain the alkynylated second-generation polyamide-amine grafted folic acid. Dendrimer;

[0045] (2) Preparation of alkynylated second-generation amide-amine dendrimer (PAMAM-GPLGVRGDGG-mPEG) grafted with matrix metalloproteinase-2 responsive peptide by polyethylene glycol monomethyl ether 4000 )

[0046] First, 250 mg azide polyethylene glycol 4000 monomethyl ...

Embodiment 2

[0055] ACC@DOX.Fe prepared in test example 1 2+ -CaSi-PAMAM-GPLGVRGDGG-PAMAM-FA / mPEG 4000 In vitro drug release properties

[0056] The ACC@DOX.Fe prepared in embodiment 1 2+ -CaSi-PAMAM-GPLGVRGDGG-PAMAM-FA / mPEG 4000 Disperse in buffers of different pH (pH=7.4 and pH=5.5) to a concentration of 0.4 mg / mL. Take 0.2mL at the corresponding time point, centrifuge at a speed of 8000rpm for 5min, and use a fluorescence spectrophotometer to detect the concentration of DOX in the supernatant, the results are as follows: figure 2 shown by figure 2 It can be seen that under the physiological condition of pH=7.4, the drug will not be released basically. Under the acidic condition of tumor cell lysosome (pH=5.5), the nanoparticles will dissociate to accelerate the release of the drug, and the cumulative release amount in 24 hours is close to 70%.

Embodiment 3

[0058] (1) Preparation of ACC-CaSi-PAMAM-GPLGVRGDGG-PAMAM-FA / mPEG 4000

[0059] The difference with Example 1 is that, do not add two kinds of raw materials of doxorubicin hydrochloric acid solution and anhydrous ferrous chloride in step (3), make amorphous calcium carbonate nano-particle, then in step (4) will " carry adriamycin Amorphous calcium carbonate composite nanoparticles of mycin and ferrous ions" were replaced by "amorphous calcium carbonate nanoparticles" to obtain ACC-CaSi-PAMAM-GPLGVRGDGG-PAMAM-FA / mPEG 4000 .

[0060] (2) Preparation of ACC@DOX-CaSi-PAMAM-GPLGVRGDGG-PAMAM-FA / mPEG 4000

[0061] The difference with Example 1 is that anhydrous ferrous chloride is not added in the step (3), and the amorphous calcium carbonate composite nanoparticles loaded with doxorubicin are obtained, and then "loaded with doxorubicin, "Amorphous calcium carbonate composite nanoparticles loaded with ferrous iron ions" was replaced with "amorphous calcium carbonate composite nan...

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Abstract

The invention relates to an amorphous calcium carbonate composite nano-medicine with an effect of inducing ferroptosis of tumor cells and a preparation method of the amorphous calcium carbonate composite nano-medicine, and belongs to the technical field of medicines. After the composite nano-medicine enters the tumor cells, the degradation of nanoparticles is promoted by means of the acidic environment of lysosomes, meanwhile, the lysosomes are subjected to permeabilization to release doxorubicin and ferrous ions through the protonation of dendrimers, wherein ferrous ions can promote the conversion of polyunsaturated fatty acids of cell membranes to lipid peroxides and induce ferroptosis of the tumor cells, and DOX can promote oxidative stress to increase the content of hydrogen peroxide in the cells while inducing apoptosis, so that iron-dependent ferroptosis caused by lipid peroxidation induced by the ferrous irons is further enhanced. The composite nanoparticles can not only increase the therapeutic effect of tumors, but also reduce the side effects caused by chemotherapy.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an amorphous calcium carbonate composite nano-medicine with the effect of inducing ferroptosis of tumor cells and a preparation method thereof. Background technique [0002] At present, multifunctional composite nanomaterials are widely used in the diagnosis and treatment of tumors. Compared with traditional chemotherapy, composite nanomaterials can effectively accumulate in tumor tissues, and release loaded drugs under the stimulation of the internal and external environments of the tumor site to enhance tumor therapy. effect, while reducing the side effects of chemotherapy. As a biodegradable and non-toxic biomaterial, calcium carbonate has a wide range of biological applications. Amorphous calcium carbonate has the characteristics of high drug loading and controllable morphology, and is a good drug delivery tool. [0003] Ferroptosis is an iron-dependent form of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/704A61K33/26A61K47/02A61K47/54A61K47/60A61P35/00B82Y5/00
CPCA61K47/60A61K47/545A61K47/6935A61K31/704A61K33/26A61K47/02A61P35/00B82Y5/00A61K2300/00
Inventor 罗忠薛臣成李孟桓侯彦华
Owner CHONGQING UNIV
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