Advanced Science (Jul 2022)
Functionalized Macrophage Exosomes with Panobinostat and PPM1D‐siRNA for Diffuse Intrinsic Pontine Gliomas Therapy
- 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
Affiliations
- Shaobo Shan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering & School of Engineering Medicine & Shenzhen Institute of Beihang University Beihang University Beijing 100083 P. R. China
- Junge Chen
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering & School of Engineering Medicine & Shenzhen Institute of Beihang University Beihang University Beijing 100083 P. R. China
- Yu Sun
- Pediatric Epilepsy Center Peking University First Hospital No.1 Xi'an Men Street, Xicheng District Beijing 100034 P. R. China
- Yongchao Wang
- Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 P. R. China
- Bozhang Xia
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Hong Tan
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Changcun Pan
- Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 P. R. China
- Guocan Gu
- Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 P. R. China
- Jie Zhong
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Guangchao Qing
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Yuxuan Zhang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Jinjin Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Yufei Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Yi Wang
- Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 P. R. China
- Pengcheng Zuo
- Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 P. R. China
- Cheng Xu
- Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 P. R. China
- Fangzhou Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- Weisheng Guo
- Department of Minimally Invasive Interventional Radiology College of Biomedical Engineering & The Second Affiliated Hospital Guangzhou Medical University Guangzhou 510260 P. R. China
- Lijun Xu
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering & School of Engineering Medicine & Shenzhen Institute of Beihang University Beihang University Beijing 100083 P. R. China
- Meiwan Chen
- State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macau 999078 P. R. China
- Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering & School of Engineering Medicine & Shenzhen Institute of Beihang University Beihang University Beijing 100083 P. R. China
- Liwei Zhang
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering & School of Engineering Medicine & Shenzhen Institute of Beihang University Beihang University Beijing 100083 P. R. China
- Xing‐Jie Liang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. China
- DOI
- https://doi.org/10.1002/advs.202200353
- Journal volume & issue
-
Vol. 9,
no. 21
pp. n/a – n/a
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.
Keywords
- blood–brain barrier
- diffuse intrinsic pontine glioma
- macrophage exosomes
- panobinostat
- siRNA blood‐brain barrier
