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A tumor-targeting polypeptide photosensitizer bond

A peptide photosensitizer and tumor-targeting technology, which is applied in the field of biomedicine, can solve the problems of ineffective enrichment and achieve targeted enrichment, transmembrane delivery, and simple preparation methods

Active Publication Date: 2017-11-28
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, traditional drug carriers use matrix metalloproteinases to specifically recognize and cut polypeptides to achieve controlled release of carrier drug molecules, and the released small molecules usually achieve transmembrane transport through diffusion, so they cannot be effectively transported. Achieve intracellular enrichment

Method used

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  • A tumor-targeting polypeptide photosensitizer bond
  • A tumor-targeting polypeptide photosensitizer bond
  • A tumor-targeting polypeptide photosensitizer bond

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Positively charged polypeptide photosensitizer bond (protoporphyrin-arginine-arginine-arginine-arginine-arginine-arginine-arginine-arginine-arginine -Glycine-Proline-Leucine, LPGR 9 -PpIX) Synthesis:

[0030] (1) Add 0.5 g of 2-chloro-trityl chloride resin (1.05 mmol / g) to a reactor containing 10 mL of re-evaporated N,N-dimethylformamide, and wait until 2-chloro-trityl chloride The benzyl chloride resin was swelled in N,N-dimethylformamide for 2h and then the N,N-dimethylformamide was removed.

[0031] (2) Dissolve FMOC-protected leucine (4 times the equivalent of the active site of the resin) and N,N-diisopropylethylamine (4 times the equivalent of the amino acid) in 10 mL of N,N-dimethylformamide Then add it to the reactor to react at room temperature for 2h to bond leucine to the resin, remove the solvent, and wash with N,N-dimethylformamide for 2 to 4 times.

[0032] (3) Add 10 mL of methanol / N,N-dimethylformamide / N,N-diisopropylethylamine in the ratio of 1:7:2 (V / V / V) i...

Embodiment 2

[0040] Positively charged [Arginine] 9 Polypeptide (cell penetrating peptide), negatively charged [glutamate] 8 Peptides and matrix metalloproteinases specifically recognize the photosensitizer bond of the polypeptide proline-leucine-glycine-leucine-alanine-glycine (protoporphyrin-arginine-arginine-arginine) -Arginine-arginine-arginine-arginine-arginine-arginine-glycine-proline-leucine-glycine-leucine-alanine-glycine-glutamic acid -Glutamate-glutamate-glutamate-glutamate-glutamate-glutamate-glutamate, U-PpIX) synthesis:

[0041] (1) Add 0.5 g of 2-chloro-trityl chloride resin (1.05 mmol / g) to a reactor containing 10 mL of re-steamed N,N-dimethylformamide, and wait until 2-chloro-trityl chloride The benzyl chloride resin was swelled in N,N-dimethylformamide for 2h and then the N,N-dimethylformamide was removed.

[0042] (2) The first amino acid is bonded to the resin: FMOC-protected glutamic acid (4 times equivalent of the active site of the resin) and N,N-diisopropylethylamine (4 ...

Embodiment 3

[0052] Human fibrosarcoma (HT 1080) cells are 1×10 5 The density of each cell / well was seeded in a 6-well plate and cultured in 1 mL of RPMI-1640 medium at 37°C. After 24h, add 1 mL of PpIX and LPGR dissolved in the culture medium equivalent to the concentration of 10mg / L PpIX into each well of the 6-well plate. 9 -PpIX, U-PpIX, and a blank control (add 1mL medium). After 1h of endocytosis, the PpIX and LPGR in the wells 9 -PpIX or U-PpIX is washed clean, and then digested with 0.25% trypsin for 1 min. Centrifuge at low speed, wash the cells three times with PBS, and finally redisperse the cells in 0.3mL PBS. Use flow cytometry to measure the PpIX or PpIX bond in the cells. Flowjo 7.6 software measures the PpIX or PpIX in the cells. The PpIX bond is quantitatively analyzed.

[0053] See the result figure 1 : LPGR containing positively charged peptides 9 -PpIX bond can enhance the endocytosis of protoporphyrin in HT 1080 cells; for HT 1080 cells with overexpression of matrix meta...

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Abstract

The invention discloses a tumor-targeting polypeptide photosensitizer bond, which belongs to the field of biomedicine. The structure of the tumor-targeting polypeptide photosensitizer bond is A-B-C-D, wherein A is a photodynamic therapy photosensitizer, B is a positively charged cell-penetrating peptide fragment, and C is a matrix metal Proteases specifically recognize polypeptide fragments, and D is a negatively charged polypeptide fragment. The polypeptide photosensitizer bond disclosed by the invention can significantly improve the stability of the photosensitizer for photodynamic therapy under physiological conditions, and greatly reduce the toxic and side effects of the photosensitizer for photodynamic therapy. The invention can remarkably improve the properties of the photodynamic therapy photosensitizer crossing the cell membrane, and improve the tumor targeting properties of the photosensitizer. The invention can realize the circulation of the photosensitizer in the blood, so that the therapeutic drug can be effectively enriched in the tumor area, and the effective inhibition of the tumor can be realized, which has great significance and wide application prospect for the diagnostic imaging and targeted therapy of the tumor.

Description

Technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a tumor-targeting polypeptide photosensitizer bond. Background technique [0002] Cancer is one of the major diseases threatening human health. Targeted therapy of cancer can greatly improve the utilization rate of drugs, improve the therapeutic effect, and reduce the side effects of drugs. Therefore, the targeted therapy of cancer has become a hot topic in the medical and academic research fields in recent years. Photodynamic therapy is a safe and non-invasive treatment for tumors. In the presence of photosensitizers and oxygen, through a certain wavelength of light excitation, the photosensitizer can transfer the energy of the excited state to oxygen to form a strong oxidizing agent. The singlet oxygen or active free radicals can oxidize biological macromolecules and destroy their physiological functions, leading to cell necrosis or apoptosis, thereby achieving the purpose of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/64A61K41/00A61K49/00A61P35/00
Inventor 张先正李仕颖成红曾旋冯俊
Owner WUHAN UNIV
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