Functionalized exosome as well as preparation method and application thereof

Abstract

The invention relates to a functionalized exosome as well as a preparation method and application thereof. The functionalized exosome simultaneously expresses a low-density lipoprotein receptor targeting polypeptide and a cell-penetrating peptide, the low-density lipoprotein receptor targeting polypeptide comprises Angiopep-2, and the cell-penetrating peptide comprises a TAT polypeptide. In the functionalized exosome, the low-density lipoprotein receptor targeting polypeptide and the cell-penetrating peptide synergistically play a role, so that the dual active selectivity of the functionalized exosome to the blood-brain barrier and glioma cells can be enhanced, the cell membrane penetrating efficiency of the functionalized exosome can be improved, and the disease treatment effect is further improved.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and relates to a functionalized exosome and a preparation method and application thereof. Background technique [0002] Glioma is one of the most common and highly malignant primary tumors in the central nervous system. It has the characteristics of aggressive growth, difficult early diagnosis, poor treatment effect, easy recurrence and high mortality. [0003] Surgery, radiotherapy and chemotherapy are the commonly used clinical treatments. Due to the biological characteristics of glioma itself and the complexity of the central nervous system, it is difficult to remove tumor cells by surgery. The radiotherapy and chemotherapy drugs of glioma are hindered by the blood-brain barrier, and it is difficult to enter the diseased brain tissue from the peripheral blood circulation to exert therapeutic effect. The blood-brain barrier is a diverse and complex dynamic system composed of brain...

AI Technical Summary

Problems solved by technology

[0005] However, during systemic treatment with tail vein injection of exosomes, most of the exosomes are taken up by organs such as the lung and liver, and only a small part can enter the brain through the peripheral blood circulation, and wild-type exosomes lack the ability to Active targeting of tumor cells, low effective enrichment rate in the tumor part

In addition, exosomes have a double-layer biomembrane structure similar to that of body cells. Exosomes need to pass through the multi-layered cell membrane structure from the peripheral blood circulation into the local glioma, and are easy to fuse with the cell membrane and be taken up by the cells. Therefore, the There are still obstacles in exosomes as a drug delivery system

[0006] CN110934851A provides a polypeptide drug exosome nano-loading system targeting cell membranes and a preparation method thereof. The exosome nano-loading system includes exosomes loaded with lipophilic fusion polypeptides and superparamagnetic nano-iron. The fusion polypeptide is obtained by genetically engineering the fusion of polypeptide drugs and membrane-penetrating peptides, and is distributed to the surface of exosome membranes through the lipophilicity of the membrane-penetrating peptides; the superparamagnetic nano-iron is distributed on the surface of exosomes, through transferrin and The transferrin receptor on the surface of the exosome is bound to the exosome; the superparamagnetic nano-iron can make the exosome carrier have the targeting ability under the action of an external magnetic field, but the exosome nano-drug delivery system cannot pass through The efficiency of the cell membrane is low, and it is difficult to efficiently enrich at the tumor site

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