Advanced Science (Jun 2022)

Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

  • 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

DOI
https://doi.org/10.1002/advs.202105451
Journal volume & issue
Vol. 9, no. 17
pp. n/a – n/a

Abstract

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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 Fe3O4 nanoparticle‐mediated Fe2+ release. Thus, the present findings show that this system can serve as a promising platform for the treatment of glioblastoma.

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