Novel multi-drugs incorporating hybrid-structured nanofibers enhancealkylating agent activity in malignant gliomas

摘要

Background:Malignant gliomas (MGs) are highly chemotherapy-resistant. Temozolomide (TMZ) and carmustine (BiCNU) are alkylating agents clinically used for treating MGs. However, their effectiveness is restrained by overexpression of the DNA repair protein O⁶-methylguanine-DNA methyltransferase (MGMT) in tumors. O⁶-benzylguanine (O⁶-BG) is a nonreversible inhibitor of MGMT, it promotes the cytotoxicity of alkylating chemotherapy. The authors have developed a hybrid-structured nanofibrous membrane (HSNM) that sequentially delivers high concentrations of O⁶-BG, BiCNU, and TMZ in an attempt to provide an alternative to the current therapeutic options for MGs.