Functionalized Macrophage Exosomes with Panobinostat and PPM1D-siRNA for Diffuse Intrinsic Pontine Gliomas Therapy.

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.

• Authors: Shaobo Shan, Junge Chen, Yu Sun, Yongchao Wang, Bozhang Xia, Hong Tan, Changcun Pan, Guocan Gu, Jie Zhong, Guangchao Qing, Yuxuan Zhang, Jinjin Wang, Yufei Wang, Yi Wang, Pengcheng Zuo, Cheng Xu, Fangzhou Li, Weisheng Guo, Lijun Xu, Meiwan Chen, Yubo Fan, Liwei Zhang, Xing-Jie Liang
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 9 Issue 21 Pg. e2200353 (07 2022) ISSN: 2198-3844 [Electronic] Germany
• PMID: 35585670 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• RNA, Small Interfering
• Panobinostat
• PPM1D protein, human
• Protein Phosphatase 2C

Topics

• Animals
• Astrocytoma (drug therapy, genetics)
• Brain Stem Neoplasms (drug therapy, genetics)
• Diffuse Intrinsic Pontine Glioma (drug therapy, genetics)
• Exosomes (chemistry, genetics)
• Glioma (drug therapy, genetics)
• Humans
• Macrophages (chemistry, metabolism)
• Mice
• Panobinostat (therapeutic use)
• Protein Phosphatase 2C (genetics, therapeutic use)
• RNA, Small Interfering (genetics, therapeutic use)