A kind of enzyme-responsive self-assembly peptide and its application

A composition and hydrophobic technology, applied in the field of nanomaterials, can solve the problems of high toxicity and side effects, damage to normal organisms, poor targeting, etc., and achieve the effect of reducing side effects

Active Publication Date: 2019-09-10
CHINA UNIV OF PETROLEUM (EAST CHINA)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chemotherapy is an important means of tumor treatment. However, the current anti-tumor drugs have disadvantages such as poor targeting, high toxicity and side effects, which can easily damage human immunity, damage the normal body, and cause symptoms such as nausea, vomiting, hair loss, and physical weakness in patients.

Method used

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  • A kind of enzyme-responsive self-assembly peptide and its application
  • A kind of enzyme-responsive self-assembly peptide and its application
  • A kind of enzyme-responsive self-assembly peptide and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: the preparation of polypeptide and nanofiber

[0028] The molecular structure of the polypeptide is as follows

[0029]

[0030] Its molecular synthesis method is as follows:

[0031] (1) Weigh 0.7861 g of MBHA resin; prepare a DMF solution of the following substances with a concentration of 0.2 mol / L: A) Fmoc-Phe-OH volume 21 mL, mass 1.63 g; B) Fmoc-Lys(Boc)-OH volume 21 mL, mass 1.97g; C) Fmoc-Pro-OH volume 11 mL, mass 0.74g; D) Fmoc-Leu-OH volume 21 mL, mass 1.48g; E) Fmoc-Gly-OH volume 11 mL, mass 0.65 g; F) Fmoc-Ala-OH volume 11mL, mass 0.68g; G) Fmoc-Arg(Pbf)-OH volume 15mL, mass 1.95g; H) Nap-CH 2 COOH has a volume of 11mL and a mass of 0.41g. Thoroughly stir to dissolve, amino acids are calculated as 2 times the amount to ensure full reaction.

[0032] (2) Prepare the following synthetic reagents: ① Activator: 0.45 mol / L, take 8.54 g of HBTU and 3.04 g of HOBt and dissolve in 50 mL of DMF; ② Activator: 2 mol / L, take 8.7 mL of diisopropyl E...

Embodiment 2

[0037] Embodiment 2: the preparation of pharmaceutical composition

[0038] The method involves mixing a drug molecule solution with Nap-Phe-Phe-Gly-Pro-Leu-Gly-Leu-Ala-Arg-Lys-Arg-Lys-NH 2 Polypeptide Molecule Contact. Solubilization loading of drug molecules by self-assembled structures:

[0039] (1) Dissolve 1 mg of doxorubicin hydrochloride or paclitaxel in 1 mL of dimethyl sulfoxide, mix with 30 μL of triethylamine, and place in the dark at room temperature for 8 hours to obtain a solution.

[0040] (2) Take 5 mg Nap-Phe-Phe-Gly-Pro-Leu-Gly-Leu-Ala-Arg-Lys-Arg-Lys-NH 2 Peptides were added to 500 μL of the above-prepared doxorubicin hydrochloride dimethyl sulfoxide solution or paclitaxel dimethyl sulfoxide solution, and phosphate buffer solution (pH 7.0, ionic strength 10 mM) was used with a dialysis bag (molecular weight cut-off 1 KDa). During dialysis, the buffer solution was changed every 3 hours to remove the unembedded doxorubicin or paclitaxel, and the nano drug c...

Embodiment 3

[0042] Embodiment 3: cell experiment

[0043] (1) Cell experiment: first inoculate 100 uL in a sterile 96-well plate with a density of 1×10 5 Hela (cervical cancer cells), A549 (non-small cell lung cancer cells), NIH 3T3 (mouse embryonic fibroblasts) and COS7 (monkey kidney fibroblasts) cells / mL were placed in a 37°C incubator for 24 hours, After it adheres to the wall, suck out the culture solution in the well plate, add 100uL of fresh culture solution and different volumes of polypeptide nanocarrier solution embedded with doxorubicin into each well, and set up 4 parallel wells for each concentration. Abs drug , In addition, the wells that only added buffer Tris and no peptide were used as the control group Abs Tris , and then put the orifice plate back in the incubator at 37°C for 24 hours. After the effect was completed, add 20 uL of MTT solution with a concentration of 5 mg / mL to each well, and continue to cultivate in the incubator for 4 hours. After that, the liqui...

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Abstract

The invention provides an enzyme-responsiveness self-assembly peptide and application thereof. The sequence of the peptide is Nap-Phe-Phe-Gly-Pro-Leu-Gly-Leu-Ala-Arg-Lys-Arg-Lys-NH2 (Nap is naphthyl), and the peptide belongs to a cationoid amphipathy oligopeptide. The antimicrobial peptide has the advantages of an excellent self-assembly capability, self-assembly nanofiber capable of containing a great quantity of hydrophobic drug molecules, and a self-assembly structure capable of changing and releasing the drug molecules under the effect of matrix metalloproteinase, wherein compared with the matrix metalloproteinase excessively expressed by normal cells, the matrix metalloproteinase excessively expressed by the cancer cells can more effectively facilitate enzymolysis of the self-assembly structure of polypeptide to release therapeutic drugs, and therefore, a selective killing effect on cancer cells can be achieved under the condition of appropriate dosages.

Description

technical field [0001] The invention belongs to the field of nanomaterial research, and in particular relates to a cationic amphiphilic self-assembled short peptide and its application as an enzyme-responsive drug carrier for cancer cell targeted drug delivery. Background technique [0002] Cancer is one of the major diseases that endanger human life and health and seriously threatens human health. Chemotherapy is an important means of tumor treatment. However, the current anti-tumor drugs have disadvantages such as poor targeting, high toxicity and side effects, which can easily damage human immunity, damage the normal body, and cause symptoms such as nausea, vomiting, hair loss, and physical weakness in patients. . Therefore, it is one of the great challenges facing the research and development of anticancer drugs to realize the targeted drug delivery to tumor tissues by enriching the drugs in tumor tissues through appropriate carrier selection and avoiding damage to othe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08C07K1/06C07K1/04A61K9/51A61K47/42A61K31/704A61K31/337A61P35/00
Inventor 曹美文赵文婧谢子龙卢沙徐海
Owner CHINA UNIV OF PETROLEUM (EAST CHINA)
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