Combined Strategies for Nanodrugs Noninvasively Overcoming the Blood-Brain Barrier and Actively Targeting Glioma Lesions.

Drugs for tumor treatment face various challenges, including poor solubility, poor stability, short blood half-life, nontargeting ability, and strong toxic side effects. Fortunately, nanodrug delivery systems provide excellent solution to these problems. However, nanodrugs for glioma treatment also face some key challenges including overcoming the blood-brain barrier (BBB) and, specifically, accumulation in glioma lesions. In this review, we systematically summarize the advantages and disadvantages of combined strategies for nanodrugs noninvasively overcoming BBB and actively targeting glioma lesions to achieve effective glioma therapy. Common noninvasive strategies for nanodrugs overcoming the BBB include bypassing the BBB via the nose-to-brain route, opening the tight junction of the BBB by focused ultrasound with microbubbles, and transendothelial cell transport by intact cell loading, ligand decoration, or cell membrane camouflage of nanodrugs. Actively targeting glioma lesions after overcoming the BBB is another key factor helping nanodrugs accurately treat in situ gliomas. This aim can also be achieved by loading nanodrugs into intact cells and modifying ligand or cell membrane fragments on the surface of nanodrugs. Targeting decorated nanodrugs can guarantee precise glioma killing and avoid side effects on normal brain tissues that contribute to the specific recognition of glioma lesions. Furthermore, the challenges and prospects of nanodrugs in clinical glioma treatment are discussed.