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Small: a translatable dual inhibitory system (TDS) based on self-assembled peptides can effectively inhibit the metastasis of renal cell carcinoma

wallpapers Cruise 2020-10-11
90% of

patients died of tumor metastasis. High vascularization of tumor tissue tumor stem cells (CSCs) are two major risk factors for accelerating tumor metastasis. Due to the high vascularization of tumor tissue the rapid proliferation of vascular endothelial cells the tumor blood vessels are immature the endothelial permeability is high. Therefore the tumor cells are easy to enter the blood circulation through the blood vessels then lead to tumor metastasis. Tumor stem cells are a kind of cell subpopulation with high degree of malignancy in tumor which have strong metastatic ability can promote distant metastasis of tumor cells by paracrine. At present tumor stem cells are regarded as the initiating factor of tumor metastasis. Clear cell renal cell carcinoma is the most common type of renal cell carcinoma with high vascular density accounting for about 80% of all cases. About 30% of the patients had metastasis when diagnosed. At the same time there are a large number of CSCs in metastatic renal cell carcinoma which leads to worse clinical prognosis. Therefore it is of great significance to inhibit the proliferation metastasis of renal cell carcinoma by inhibiting both renal cancer stem cells tumor blood vessels.

national nanoscience center Wang Hao research group Professor Xu Wanhai research group of the Fourth Affiliated Hospital of Harbin Medical University carried out in-depth research on the characteristics of metastatic renal cell carcinoma developed a new nano material based on self-assembled peptides named TDS (transformable dual inhibition system). This material can simultaneously target CD105 a common surface marker of renal cell carcinoma neovascular endothelial cells tumor stem cells. Through lig receptor binding self-assembly deformation occurs on the cell membrane nanofiber barrier is constructed in situ. It helps to reduce the endothelial permeability angiogenesis of renal cell carcinoma neovascular endothelial cells inhibit the dryness metastasis of renal cell carcinoma CSCs ultimately inhibit the growth of renal cell carcinoma Metastasis provides the possibility of targeting endothelial cells CSCs for tumor therapy.

The results of

experiment in vitro showed that TDS reduced the vascular permeability by 67.0 ± 4.7% angiogenesis by 62.0 ± 4.0% effectively reduced the vascular permeability angiogenesis significantly inhibited the high vascularization of tumor; for human CSCs TDS reduced the number of CSCs spheroidization by 2.4 times the number of migrating cells invasive cells to 45.5% ± 1.8% respectively Compared with 37.3% ± 7.2% CSCs significantly reduced the dryness invasion ability. TDS significantly inhibited tumor development angiogenesis in patient derived xenograft (PDX) mice. Compared with the control group the microvessel density (MVD) of the tumor was significantly reduced by TDS the tumor volume was reduced to 24.3% ± 7.4% the lung metastasis was also reduced by 5.0 times. Therefore TDS can effectively inhibit tumor angiogenesis tumor growth significantly reduce the occurrence of tumor metastasis.

to sum up the self-assembled peptide based translatable double inhibition system (TDS) constructed in this work can significantly inhibit tumor vascular permeability angiogenesis inhibit the stem cells of CSCs reduce the occurrence of tumor metastasis provide the possibility of targeting endothelial cells CSCs for the treatment of metastatic renal cell carcinoma provide a new idea for the targeted treatment of other types of tumor. The related work is supported by Heilongjiang applied technology research development program National Natural Science Foundation of China China Postdoctoral Science Foundation.

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