Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
Functionalized Macrophage Exosomes with Panobinostat and PPM1D-siRNA for Diffuse Intrinsic Pontine Gliomas Therapy.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Shan Shaobo, Chen Junge, Sun Yu, Wang Yongchao, Xia Bozhang, Tan Hong, Pan Changcun, Gu Guocan, Zhong Jie, Qing Guangchao, Zhang Yuxuan, Wang Jinjin, Wang Yufei, Wang Yi, Zuo Pengcheng, Xu Cheng, Li Fangzhou, Guo Weisheng, Xu Lijun, Chen Meiwan, Fan Yubo, Zhang Liwei, Liang Xing-Jie
Аннотация
Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brain tumor. Mutation of p53-induced protein phosphatase 1 (PPM1D) in DIPG cells promotes tumor cell proliferation, and inhibition of PPM1D expression in DIPG cells with PPM1D mutation effectively reduces the proliferation activity of tumor cells. Panobinostat effectively kills DIPG tumor cells, but its systemic toxicity and low blood-brain barrier (BBB) permeability limits its application. In this paper, a nano drug delivery system based on functionalized macrophage exosomes with panobinostat and PPM1D-siRNA for targeted therapy of DIPG with PPM1D mutation is prepared. The nano drug delivery system has higher drug delivery efficiency and better therapeutic effect than free drugs. In vivo and in vitro experimental results show that the nano drug delivery system can deliver panobinostat and siRNA across the BBB and achieve a targeted killing effect of DIPG tumor cells, resulting in the prolonged survival of orthotopic DIPG mice. This study provides new ideas for the delivery of small molecule drugs and gene drugs for DIPG therapy.