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  2. Heme Oxygenase-1 targeting exosomes for temozolomide resistant glioblastoma synergistic therapy

Heme Oxygenase-1 targeting exosomes for temozolomide resistant glioblastoma synergistic therapy

  • J Control Release. 2022 May;345:696-708. doi: 10.1016/j.jconrel.2022.03.036.
Fawad Ur Rehman 1 Yang Liu 1 Qingshan Yang 1 Haoying Yang 1 Runhan Liu 1 Dongya Zhang 1 Pir Muhammad 1 Yanjie Liu 1 Sumaira Hanif 1 Muhammad Ismail 1 Meng Zheng 2 Bingyang Shi 3
Affiliations

Affiliations

  • 1 Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, Henan 475004, China.
  • 2 Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, Henan 475004, China. Electronic address: mzheng@henu.edu.cn.
  • 3 Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Macquarie Medical School, Faculty of Medicine & Health Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: bs@henu.edu.cn.
Abstract

Glioblastoma (GBM) is a highly fatal and recurrent brain Cancer without a complete prevailing remedy. Although the synthetic nanotechnology-based approaches exhibit excellent therapeutic potential, the associated cytotoxic effects and organ clearance failure rest major obstacles from bench to clinics. Here, we explored allogeneic bone marrow mesenchymal stem cells isolated exosomes (BMSCExo) decorated with heme oxygenase-1 (HMOX1) specific short peptide (HSSP) as temozolomide (TMZ) and small interfering RNA (siRNA) nanocarrier for TMZ resistant glioblastoma therapy. The BMSCExo had excellent TMZ and siRNA loading ability and could traverse the blood-brain barrier (BBB) by leveraging its intrinsic brain accumulation property. Notably, with HSSP decoration, the TMZ or siRNA encapsulated BMSCExo exhibited excellent TMZ resistant GBM targeting ability both in vitro and in vivo due to the overexpression of HMOX1 in TMZ resistant GBM cells. Further, the HSSP decorated BMSCExo delivered the STAT3 targeted siRNA to the TMZ resistant glioma and restore the TMZ sensitivity, consequently achieved the synergistically drug resistant GBM treatment with TMZ. Our results showed this biomimetic nanoplatform can serve as a flexible, robust and inert system for GBM treatment, especially emphasizing the drug resistant challenge.

Keywords

Exosome; Glioblastoma; HMOX1; Temozolomide resistance; siRNA.

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