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Tumor-targeting cell drug carrier and application thereof

A tumor targeting and drug technology, applied in the field of biomedicine, can solve the problems such as charging properties, hydrophilicity and hydrophobicity affecting the drug loading rate of cell carriers, carrier cells cannot achieve long-term in vivo circulation, and limiting the application significance of cell drug carriers, etc. Easy to purify, easy to obtain, simple to prepare

Active Publication Date: 2017-02-22
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The traditional cellular drug carrier achieves the drug entrapment and release through the endocytosis and diffusion of the therapeutic drug by the carrier cells, which greatly limits the application significance of this cellular drug carrier
First of all, this kind of cell drug carrier has high requirements on cells and drugs, so usually only monocytes or macrophages can be used as cell carriers, and it can only be limited to photothermal therapy and the transportation of certain chemotherapy drugs; secondly, The toxicity of the drug to the carrier cells makes the carrier cells unable to achieve long-term internal circulation; again, because the endocytic drug is in a complex intracellular environment, and the active enzymes in the carrier cells such as lysosomes and endosomes will cause the drug to remain in the carrier. The degradation in the cell also makes it difficult for the drug to escape from the subcellular organelles of the carrier cell; finally, the charged properties and hydrophilicity and hydrophobicity of the drug also greatly affect the drug loading rate of the cell carrier

Method used

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  • Tumor-targeting cell drug carrier and application thereof
  • Tumor-targeting cell drug carrier and application thereof
  • Tumor-targeting cell drug carrier and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] [Example 1] Synthesis of Embedded Cell Membrane Bonding Compound

[0056] Cell-embedded membrane bond (palmitic acid-lysine (camptothecin)-arginine-arginine-arginine-arginine), (palmitic acid-lysine (protoporphyrin)-arginine Synthesis of acid-arginine-arginine-arginine) and (palmitic acid-lysine (fluorescein)-arginine-arginine-arginine-arginine):

[0057] (1) Add 0.5 g of chlorine resin (1.01 mmol / g) to a reactor containing 10 mL of double-distilled N,N-dimethylformamide, and wait for the chlorine resin to dissolve in N,N-dimethylformamide N,N-dimethylformamide was withdrawn after 2 hours of swelling.

[0058] (2) Dissolve FMOC-protected amino group and Pbf-protected guanidino arginine (4 times equivalent of resin active site), N,N-diisopropylethylamine (8 times equivalent of amino acid) in 10 mL N,N - in dimethylformamide, and then put into the reactor at room temperature to react for 2 hours to bond cysteine ​​to the resin, extract the solvent, and wash with N,N-dim...

Embodiment 2

[0070] [Example 2] Embedded cell membrane camptothecin bonded macrophage membrane and its stability over time

[0071] Macrophages were treated at 1×10 5 Cells / well were seeded at a density of 37°C in 1 mL of culture medium. After 24 hours, the cell-embedded camptothecin conjugate was dissolved in the medium, and 1 mL of the medium containing the cell-embedded camptothecin conjugate (30 μmol / L) was added to the macrophages. After culturing for 2 hours, aspirate the culture medium containing the camptothecin bond embedded in the cell membrane, wash the cells three times with PBS buffer solution, add new medium, and observe the fluorescence intensity of camptothecin in the cells with a laser confocal microscope .

[0072] The result is as figure 1 As shown, the embedded cell membrane camptothecin conjugate can be effectively embedded in the macrophage cell membrane. At the same time, the fluorescence intensity on the cell membrane surface is only weakly reduced when the cultu...

Embodiment 3

[0073] [Example 3] Embedded cell membrane protoporphyrin bonded macrophage and its stability over time

[0074] Macrophages were treated at 1×10 5 Cells / well were seeded at a density of 37°C in 1 mL of culture medium. After 24 hours, the cell-embedded membrane protoporphyrin conjugate was dissolved in the medium, and 1 mL of the medium containing the cell-embedded membrane protoporphyrin conjugate (30 μmol / liter) was added to the macrophages. After culturing for 2 hours, suck out the medium containing protoporphyrin bonds embedded in the cell membrane, wash the cells three times with PBS buffer solution, add new medium, and observe the fluorescence intensity of protoporphyrin in the cells with a laser confocal microscope .

[0075] The result is as figure 2 As shown, the cell-embedded protoporphyrin bond can be effectively embedded in the macrophage cell membrane, and at the same time, the fluorescence intensity on the cell membrane surface is only weakly reduced as the cu...

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Abstract

The invention discloses a tumor-targeting cell drug carrier and an application thereof. The drug carrier is prepared from a cytomembrane-embedded drug bonding material and a carrier cell, the cytomembrane-embedded drug bonding material is prepared from hydrophilia polypeptide, an alkyl chain and a bonding drug, and embedded into the cytomembrane of the carrier cell, and drug delivery is achieved through the tropism of the carrier cell for tumor. The tumor-targeting cell drug carrier can simultaneously deliver any two bonding drugs of a photodynamics treatment photosensitizer, a chemotherapy drug and a fluorescent molecular to tumor; enrichment of drugs at the tumor region is achieved, the treatment effect of drugs is improved, and the side effect of drugs is reduced. A preparing method of the cytomembrane-embedded drug bonding material is simple, practicable, high in yield and easy to purify. The cell drug carrier is of great significance in promoting accurate treatment of tumor and achieving personalized treatment.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a tumor-targeting cell drug carrier and its application. Background technique [0002] Tumor is a major disease that threatens human health. To achieve targeted therapy of tumors and reduce the damage of therapeutic drugs to normal tissues and organs is of great significance to overcome the major problem of tumor diseases. Chemotherapy drugs, radiotherapy drugs, and photodynamic therapy drugs have been widely used in the treatment of tumors, which can inhibit the growth of tumors to a certain extent. However, the drugs used in the process of tumor treatment are usually not selective, and in order to achieve effective tumor suppression, it is necessary to increase the dosage of the therapeutic drugs. The strong toxic side effects in the process of tumor treatment not only greatly reduce the effect of tumor treatment, but also reduce the quality of life of tumor patients. T...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/62A61K47/46A61K41/00A61K31/4745A61P35/00A61K49/00
Inventor 张先正李仕颖邱文秀曾旋
Owner WUHAN UNIV
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