Overcoming the blood–brain barrier for glioma-targeted therapy based on an interleukin-6 receptor-mediated micelle system†
Abstract
Treatments of cancer in the central nervous system (CNS), such as glioma, require nano-drugs to efficiently cross the blood–brain barrier (BBB) and highly accumulate within tumor regions. In this work, a new interleukin-6 receptor-mediated micelle system, where a short peptide I6P8 was conjugated to biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG–PLGA), was prepared for cascade-targeting drug delivery to glioma. In vitro results showed that the I6P8-conjugated doxorubicin (DOX)-loaded micelle (I6P8-D-M) could significantly transport across the BBB and subsequently target the glioma cells, which was superior to results of scrambled peptide-modified counterparts. While in vivo results confirmed that this multifunctional I6P8-D-M could introduce the highest glioma apoptosis and longest survival of glioma-bearing mice as compared to other groups. These findings suggest that the I6P8-D-M micelle system is a promising cascade-targeting therapeutic agent, which can overcome the BBB for glioma-targeted therapy.