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Bionic binary cooperative nano-carrier as well as preparation method and application thereof

A nano-carrier and nano-particle technology, applied in the field of bionic binary synergistic nano-carriers and its preparation, can solve problems such as normal tissue damage, achieve precise treatment, avoid damage, and improve the effect of enrichment

Active Publication Date: 2018-11-16
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The primary purpose of the present invention is to overcome the shortcomings and deficiencies of the prior art, solve the problem that the existing cancer chemotherapy drugs will cause certain damage to normal tissues during the circulation process in the body, and provide a bionic binary synergistic nanocarrier, the nanocarrier The binary synergistic therapy that produces chain stimulus responsiveness will be treated through the generated hydroxyl free radicals, which will not produce drug resistance, have no toxicity to normal tissues, and effectively avoid damage to other normal tissues during the internal circulation process

Method used

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  • Bionic binary cooperative nano-carrier as well as preparation method and application thereof
  • Bionic binary cooperative nano-carrier as well as preparation method and application thereof
  • Bionic binary cooperative nano-carrier as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1I

[0039] Example 1 Preparation of ICG Membrane Breaking Biomimetic Binary Synergistic Nanocarrier

[0040] 1. Preparation of apoferritin nanocages (HFn) and ferritin nanoparticles (M-HFn)

[0041] (1) Preparation of apoferritin nanocages (HFn) by genetic engineering

[0042] The positive strain expressing apoferritin nanocages was constructed by Hubei Bios Biotechnology Co., Ltd., which provides services such as plasmid construction, and the cells are also derived from this company.

[0043] RNA was extracted from human skeletal muscle cells, reverse-transcribed into cDNA as a template; human FTH1 gene was amplified, and the PCR primers were as follows (the black underline is the restriction site):

[0044] F:5'-A GTC GCC CAT ATG ACG ACC GCG TCC-3'(Nde I)

[0045] R:5'-GCC GGA TCC TTA GCT TTC ATT ATCA C-3'(Bam HI)

[0046] After the PCR product was purified and recovered, it was ligated with the pET-30a(+) carrier by double enzyme digestion, and the product was transfor...

Embodiment 2

[0058] Example 2 Preparation of DIR Membrane Breaking Biomimetic Binary Synergistic Nanocarriers

[0059] 1. Preparation of apoferritin nanocages (HFn) and ferritin nanoparticles (M-HFn)

[0060] (1) Preparation of apoferritin nanocages by genetic engineering

[0061] RNA was extracted from human skeletal muscle cells, reverse-transcribed into cDNA as a template; human FTH1 gene was amplified, and the PCR primers were as follows (the black underline is the restriction site):

[0062] F:5'-A GTC GCC CAT ATG ACG ACC GCG TCC-3'(Nde I)

[0063] R:5'-GCC GGA TCC TTA GCT TTC ATT ATCA C-3'(Bam HI)

[0064] After the PCR product was purified and recovered, it was ligated with the pET-30a(+) carrier by double enzyme digestion, and the product was transformed into XL2-Blue competent cells, screened on a Kan+ resistance plate, and colonies were picked and identified before being sent for sequencing. The plasmids with correct sequencing were transferred into competent BL21(DE3)E....

Embodiment 3

[0075] Embodiment 3 animal experiments

[0076] 1. Construction of BALB / c mouse subcutaneous tumor model

[0077] Prepare a single-cell suspension from tumor cells in logarithmic growth phase, wash 3 times with serum-free medium, and adjust the cell concentration to 1*10 7 / mL, animal experiments were carried out in a clean bench. Inject the cell suspension into the subcutaneous inner thigh of nude mice with a TB empty needle (choose the place with rich blood vessels), inoculate each mouse with 0.1mL, containing 1*10 cells 6 , the miliary size of subcutaneously transplanted tumors (about 10 days, about 60-80mm in size) 3 ) to start the intervention treatment, and start to measure the long diameter and short diameter of the tumor with a vernier caliper.

[0078] 2. Experimental steps

[0079] The tumor-bearing mice at the age of 4 to 6 weeks were randomly divided into 4 groups, 6 in each group, the first group was the PBS group, and the second group was the non-targeted env...

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Abstract

The invention provides a bionic binary cooperative nano-carrier as well as a preparation method and an application thereof. The bionic binary cooperative nano-carrier comprises an erythrocyte membrane, glucose oxidase, iron-supporting ferritin nano-particles and a photosensitizer, wherein the glucose oxidase and the iron-supporting ferritin nano-particles are coated with the erythrocyte membrane,and the photosensitizer is embedded into the surface of the erythrocyte membrane or entrapped by the erythrocyte membrane. Chain stimulative responsibility coordination of tumor hunger therapy and chemical kinetic therapy is realized, two enzymes are conveyed to a target site of an organism with the carrier on the basis of biocompatibility of the erythrocyte membrane and tumor targeting of targeting molecules, accurate administration is realized by membrane rupture based on 808 nm near-infrared light illumination in the tumors, the problem of drug resistance is solved effectively, furthermore,systemic toxicity caused by drug application is remarkably reduced, and damage to other normal tissue in an in-vivo circulation process is prevented effectively. The invention further provides the preparation method of the bionic binary cooperative nano-carrier. The bionic binary cooperative nano-carrier and the preparation method have good application prospect.

Description

technical field [0001] The invention relates to the technical field of nanomedicine, in particular to a bionic binary synergistic nanocarrier and its preparation method and application. Background technique [0002] Tumor chemotherapy is one of the most important technical means for clinical treatment of cancer, but there are two technical problems in the current treatment itself that need to be solved. First, how to achieve long-term circulation of drugs in the body and specific delivery to cancer cells is the key to improving drug efficacy and reducing side effects; second, chemotherapy-induced cancer cell drug resistance is an important factor leading to poor chemotherapy effects. Based on the current status quo, the design and construction of drug carriers for tumor therapy have shown a crucial position. [0003] The construction of drug carriers in tumor therapy has two important aspects. One is to reduce the damage to normal tissues, that is, to maintain a long circul...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/18A61K47/42A61K47/22A61K47/46A61P35/00A61K38/44A61K38/40
CPCA61K38/40A61K38/443A61K41/0057A61K47/183A61K47/22A61K47/42A61K47/46A61P35/00C12Y101/03004A61K2300/00
Inventor 戴箭阮淼亮薛巍宋镕光
Owner JINAN UNIVERSITY
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