Synchronous Disintegration of Ferroptosis Defense Axis Via Engineered Exosome-Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2022 May 4

PMID 35508804

Authors

Boyan Li

Xin Chen

Wei Qiu

Rongrong Zhao

Jiazhi Duan

Shouji Zhang

Ziwen Pan

Shulin Zhao

Qindong Guo

Yanhua Qi

Wenhan Wang

Lin Deng

Shilei Ni

Yuanhua Sang

Hao Xue

Hong Liu

Gang Li

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis is a newly discovered method of programmed cell death and opens a new direction for GBM treatment. However, poor blood-brain barrier (BBB) penetration, reduced tumor targeting ability, and potential compensatory mechanisms hinder the effectiveness of ferroptosis agents during GBM treatment. Here, a novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the BBB penetration abilities and siRNA encapsulation properties of engineered exosomes for GBM therapy is presented. This platform can be enriched in the brain under local magnetic localization and angiopep-2 peptide-modified engineered exosomes can trigger transcytosis, allowing the particles to cross the BBB and target GBM cells by recognizing the LRP-1 receptor. Synergistic ferroptosis therapy of GBM is achieved by the combined triple actions of the disintegration of dihydroorotate dehydrogenase and the glutathione peroxidase 4 ferroptosis defense axis with Fe O nanoparticle-mediated Fe release. Thus, the present findings show that this system can serve as a promising platform for the treatment of glioblastoma.

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