Time-sequenced drug delivery approaches towards effective chemotherapeutic treatment of glioma

Abstract

Glioma is the most common malignant brain tumor which has an overall terrible prognosis. Nevertheless, despite the tremendous research input that has been applied to treat gliomas, the efficacy of existing therapeutic modalities on real-life patients is still far from satisfactory, mostly due to several difficult obstacles unique to the CNS and gliomas themselves. Notably, the treatment efficiency of many anti-glioma chemotherapies based on small-molecule anticancer drugs is severely impaired by the blood–brain-barrier, blood–brain–tumor-barrier and resistance mechanisms related to intracranial gliomas, which prevent the therapeutic agents from gaining access to the desired site of action while aggravating associated side effects. Rationally based on the synergistic combination of multiple glioma-specific dosing approaches in chronological order, the time-sequenced targeting strategy is an emerging therapeutic paradigm to address these critical issues, which is capable of efficiently destroying the malignant glioma cells while sparing healthy brain cells and tissues. In this review, we will start with a brief introduction of the major difficulties associated with malignant gliomas and corresponding drug delivery strategies under clinical or laboratory studies, and then comprehensively summarize the recent advances in time-sequenced targeted anti-glioma nanoplatforms, in which their potential benefits and unsolved issues will both be covered.