VEGFc (vascular endothelial growth factor) protein slow-release nano-particle for improving spermatogenesis and application of nano-particle

Abstract

The invention relates to a VEGFc (vascular endothelial growth factor) protein slow-release nano-particle for improving spermatogenesis. According to the nano-particle, VEGFc and dextran sulfate are combined by a heparin-binding domain of VEGFc proteins to form close polyanions. Chitosan is combined with the polyanions by means of mutual charge attraction to form the stable nano-particle. The invention further provides an application of the nano-particle to long-term nourishment of spermatogenic cells, promotion of reproductive cell proliferation and improvement of spermatogenesis. The nano-particle has the advantages that (1) the nano-particle has good uniformity, stability and biological safety, (2) the nano-particle can slowly and stably release VEGFc factors, long-term nourishment of the spermatogenic cells can be performed in vivo, reproductive cell proliferation is promoted, so that the spermatogenesis process of an azoospermia model mouse is improved, and a reference is providedfor non-obstructive azoospermia patients caused by spermatogenic cell proliferation deficiency in clinical treatment.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a sustained-release nanoparticle of VEGFc protein for improving spermatogenesis and its application. Background technique [0002] VEGFC, a member of the vascular endothelial growth factor (VEGF) family, has attracted much attention in the past because it mediates the formation of lymphatic vessels and organs. Recent studies have found that VEGFC is also a key factor in the regulation of various cell proliferation, apoptosis and organ development. A study on neural stem cells showed that the VEGFc / VEGFR3 pathway can activate quiescent neural stem cells through an autocrine pathway, allowing them to enter the cell cycle and generate progenitor cells. In addition, the previous research of the research group of the inventor showed that in the male reproductive system, VEGFc factor can play a role in promoting proliferation and anti-apoptosis in mouse spermatogonia by binding to VE...

AI Technical Summary

Problems solved by technology

[0003] However, generally speaking, as a kind of effector protein, cytokines cannot exist stably for a long time in the environment in vivo and in vitro. Our research found that the half-life of VEGFc factor in the most common DMEM medium is only about 48 hours. That is to say, if the VEGFC factor is administered through local injection, the time to reach the concentration of the therapeutic dose in a specific tissue will usually not exceed 1 week, except for the body's own metabolism of the drug; in addition, in the testis, due to blood testis Due to the existence of the barrier, the growth factors injected directly into the space of the testicular seminiferous tubules, that is, the interstitium of the testis, often cannot reach the effective therapeutic concentration in the seminiferous tubules because it is difficult to enter the seminiferous tubules. Retrograde injection into the seminiferous tubules, but this kind of injection is an invasive operation, which has certain damage to the efferent tubules and the seminiferous tubules, and cannot be repeatedly administered for a long time

Therefore, the above factors greatly limit the physiological function of VEGFC and reduce the therapeutic effect.

[0004] The prior art has the following disadvantages: (1) VEGFc, as an active protein, has a very short half-life in a culture medium at room temperature and in vivo, according to measurement data, its half-life is only about 2 days in an in vitro culture environment, while The normal spermatogenesis cycle of a person is about 70 days. It is difficult to maintain the effective drug concentration required for local treatment for a long time with one administration. To achieve the therapeutic effect, it is necessary to inject the drug multiple times for a long time

But a kind of VEGFc protein sustained-release nanoparticle and its application for improving spermatogenesis of the present invention have not been reported yet.

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