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A few days ago, the team led by Gao Xiaoling, a researcher from the Pharmacology and Chemical Biology Department of Shanghai Jiao Tong University School of Medicine, has published an online article in Nature Communications titled Lipoprotein - Biomimetic Nanostructure Enables Efficient Targeting Delivery of siRNA to Ras - Activated Glioblastoma Cells via Macropinocytosis. Researchers have create a nanostructure carrying siRNA encapsulated by high-density lipoprotein to deliver the RNAi drugs safely into the brain, and to target at Ras-activation-dependent brain glioblastoma cells to achieve precise targeting therapy since they maintain their growth and survival in a micropinocytosis way.
Ras, the first identified oncogene in human tumors, has always been a hot topic in medicine. This study has focused on the metabolism regulated by Ras, tumor cells activated by Ras depend on the macropinocytosis to maintain growth and survival, which shows significant difference from normal cells. Therefore, it is assumed that lipoprotein-biomimetic nanostructures, like “nutrition proteins”, can be “drunk” by the cells of glioblastoma cells with high expression of Ras. According to this, the team has successfully constructedhigh-density lipoprotein nanostructure, which can penetrate the brain-blood barrier, to encapsulate a siRNA-loaded calcium phosphate core. The core, sensitivity to acid, can be dissolved in lysosomes into siRNA, calcium and phosphate ions to produce a high pressure in lysosomes in turn, which will cause the lysosome to swell and explode to release siRNA into the the cytoplasm. The high-density lipoprotein nanostructures carrying activating tranion factor 5(ATF5) exertremarkable silence effect of ATF5 in brain glioblastoma cells model, which effectively induce apoptosis of tumor cells and prolong survival time of the in situ tumor-burdened mice. Since the nanostructure carrier has overcomesome disadvantages of the usual RNAi drugs, such as easy degradation, short cycle time, poor orientation to target cells, difficulty ingoing through the brain-blood barrier and the insufficient release in the cytoplasm, it has been applied for national invention patent due to its good further.
Huang Jialing, a postgraduate student at Shanghai Jiao Tong University School of Medicine, and Jiang Gan, a postdoctoral fellow, were the first authors of the paper, with the guidance of Gao Xiaoling and Professor Chen Hongzhuan and the support of Professor Jiang Jiyao and Qiu Yongming from the affiliated Renji Hospital neurosurgery. The project is funded by the National Key Basic Research and Development Plan, the National Natural Science Foundation, the Shanghai Municipal Science and Technology Commission International Cooperation Project, Shanghai Dawn Project and Shanghai Talent Development Fund.