TY - JOUR
T1 - Heme Oxygenase-1 targeting exosomes for temozolomide resistant glioblastoma synergistic therapy
AU - Rehman, Fawad Ur
AU - Liu, Yang
AU - Yang, Qingshan
AU - Yang, Haoying
AU - Liu, Runhan
AU - Zhang, Dongya
AU - Muhammad, Pir
AU - Liu, Yanjie
AU - Hanif, Sumaira
AU - Ismail, Muhammad
AU - Zheng, Meng
AU - Shi, Bingyang
PY - 2022/5
Y1 - 2022/5
N2 - 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
AB - 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
KW - Exosome
KW - Glioblastoma
KW - HMOX1
KW - siRNA
KW - Temozolomide resistance
UR - http://www.scopus.com/inward/record.url?scp=85128985567&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2022.03.036
DO - 10.1016/j.jconrel.2022.03.036
M3 - Article
C2 - 35341901
AN - SCOPUS:85128985567
SN - 0168-3659
VL - 345
SP - 696
EP - 708
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -