D-T7 Peptide Modified PEGylated Bilirubin Nanoparticles Loaded with Cediranib and Paclitaxel for Antiangiogenesis and Chemotherapy of Glioma.

The blood brain tumor barrier (BTB) and blood-brain barrier (BBB) have always been the major barriers in the treatment of glioma. In this report, we proposed D-T7 peptide modified nanoparticles actively targeted glioma by overcoming the BBB and BTB to improve the anti-glioma efficacy. Glioma targeting experiment showed that the penetration effect of D-T7 peptide modified nanoparticles was 7.89-fold higher than that of unmodified nanoparticles. Furthermore, cediranib (CD) and paclitaxel (PTX) were used for the combination of the antiangiogenesis and chemotherapy of glioma. PEGylated bilirubin nanoparticles (BRNPs) were selected as a suitable drug delivery system (CD&PTX@TBRBPs) owing to the antioxidant, anti-inflammatory and reactive oxygen species (ROS)-responsive ability. MTT and apoptosis assays showed that CD&PTX@TBRBPs had the highest cytotoxicity and the median survival time of CD&PTX@TBRNPs group was 3.31-fold and 1.23-fold longer than that of saline and CD&PTX@BRNPs groups, respectively. All the results showed that we constructed a novel and accessible peptide-modified dual drug carrier with enhanced anti-glioma effect.