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siRNA Nanoparticle Suppresses Drug‐Resistant Gene and Prolongs Survival in an Orthotopic Glioblastoma Xenograft Mouse Model
Author(s) -
Wang Kui,
Kievit Forrest M.,
Chiarelli Peter A.,
Stephen Zachary R.,
Lin Guanyou,
Silber John R.,
Ellenbogen Richard G.,
Zhang Miqin
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202007166
Subject(s) - temozolomide , cancer research , apoptosis , chemotherapy , small interfering rna , drug resistance , dna repair , methyltransferase , cancer , pharmacology , glioblastoma , medicine , cell culture , gene , biology , transfection , biochemistry , genetics , methylation , microbiology and biotechnology
Temozolomide (TMZ) is the standard‐of‐care chemotherapy drug for treating glioblastomas (GBMs), the most aggressive cancer that affects people of all ages. However, its therapeutic efficacy is limited by the drug‐resistance mediated by a DNA repair protein, O 6 ‐methylguanine‐DNA methyltransferase (MGMT), which eliminates the TMZ‐induced DNA lesions. Here, the development of an iron oxide nanoparticle (NP) system for targeted delivery of small interfering RNAs to suppress the TMZ‐resistance gene (MGMT) is reported. The NPs are able to overcome biological barriers, bind specifically to tumor cells, and reduce MGMT expression in tumors of mice bearing orthotopic GBM serially passaged patient‐derived xenografts. The treatment with sequential administration of this NP and TMZ result in increased apoptosis of GBM stem‐like cells, reduced tumor growth, and significantly prolonged survival as compared to mice treated with TMZ alone. This study introduces an approach that holds great promise to improve the outcomes of GBM patients.