**1. Introduction**

Malignant gliomas account for more than 50% of primary central nervous system (CNS) tumors and are among the most formidable cancers in human beings (1). Although aggressive debulking surgery followed by radiation and chemotherapy is the mainstay for malignant gliomas, the prognosis of malignant gliomas remains far from satisfactory. The 5‐year overall survival (OS) is as low as 9.8% for patients with glioblastoma multiforme (GBM), a malignancy classified as grade IV by the world health organization (WHO) (2). The recurrence seems to be inevitable for malignant gliomas. Most patients with recurred GBM will die within 6 months even with salvage treatments.

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The exact mechanisms underlying the intractability of malignant gliomas have not been fully understood, but the inherent resistance and the sheltering environment of brain have been proposed to protect the disease from conventional treatments. First of all, the infiltrative growth pattern of glioma cells makes the complete surgical resection almost impossible. Second, the existence of blood–brain barrier (BBB), which is tightly formed by capillary endothelial cells together with astrocytes, restricts the entry of most systemically adminis‐ tered chemotherapeutic agents into the tumor parenchyma (3). Third, the inherent and acquired insensitivity to radiation and chemotherapy through the disturbance of signaling pathway in glioma cells results in the resistance to current therapies (4). Because gliomas seldom metastasize outside the CNS and usually recur within 1–2 cm from the original tumor site, it is reasonable to expect the efficacy of directly delivering potent chemotherapeutic drugs into the tumor mass and its adjacent area. By this means, not only a higher drug concentra‐ tion around the tumor but also a minimal systemic toxicity can be achieved.
