Functionalized Macrophage Exosomes with Panobinostat and PPM1D‐siRNA for Diffuse Intrinsic Pontine Gliomas Therapy. Issue 21 (18th May 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Advanced science. Volume 9:Issue 21(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-18
• Subjects: blood–brain barrier -- diffuse intrinsic pontine glioma -- macrophage exosomes -- panobinostat -- siRNA blood‐brain barrier; Science -- Periodicals; 505
• DOI: 10.1002/advs.202200353
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : Functionalized macrophage exosomes with panobinostat and PPM1D‐siRNA are constructed for targeted therapy of diffuse intrinsic pontine glioma (DIPG) with PPM1D mutation. The nano drug delivery system can deliver panobinostat and siRNA across the blood–brain barrier and achieve a targeted killing effect of DIPG tumor cells, resulting in the prolonged survival of orthotopic DIPG mice.