Gliomas are tumors of the central nervous system; they can be invasive and are commonly treated by surgical resection, chemo, and radiotherapy. Removal of a glioma is dangerous and not always successful. Temozolomide (TMZ), the first-line chemotherapy drug for gliomas, inhibit tumor recurrence, and metastasis to some extent. TMZ is often accompanied by side effects such as anemia, fever, constipation, and more. Here using a double-targeted Kunitz domain Angiopep-2 (ANG) modified block copolymer poly(lactic acid)-polyethylene glycol (PEG-PLA) coated with TMZ, we constructed a nano-delivery system (ANG@PLA-PEG/TMZ) that crosses the blood-brain barrier (BBB) to treat gliomas.