LAUSR

Abstract The current treatment of glioblastoma (GBM) remains challenging. Temozolomide (TMZ), a first-line chemotherapy drug used to treat glioblastoma, is rapidly cleared under normal physiological conditions and has poor stability, which severely limits its efficacy. In current work, poly(2-ethyl-2-oxazoline) (PEtOz) conjugated TMZ (PEtOz-TMZ) was synthesized and directly dissolved in PBS to form prodrug micelles. This PEtOz-TMZ conjugation did not affect the DNA alkylation of TMZ and enhanced the stability of TMZ, prolonged the circulation time in vivo and increased the TMZ accumulation in glioblastoma. In vivo, the PEtOz-TMZ micelle significantly enhanced the efficiency of TMZ to inhibit the growth of glioblastoma. These results indicate that binding to the polymer can effectively improve the efficacy and stability of TMZ, and is a promising route of administration of TMZ in clinic.