Enhanced delivery of etoposide across the blood-brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles.

Melanotransferrin antibody (MA) and tamoxifen (TX) were conjugated on etoposide (ETP)-entrapped solid lipid nanoparticles (ETP-SLNs) to target the blood-brain barrier (BBB) and glioblastom multiforme (GBM). MA- and TX-conjugated ETP-SLNs (MA-TX-ETP-SLNs) were used to infiltrate the BBB comprising a monolayer of human astrocyte-regulated human brain-microvascular endothelial cells (HBMECs) and to restrain the proliferation of malignant U87MG cells. TX-grafted ETP-SLNs (TX-ETP-SLNs) significantly enhanced the BBB permeability coefficient for ETP and raised the fluorescent intensity of calcein-AM when compared with ETP-SLNs. In addition, surface MA could increase the BBB permeability coefficient for ETP about twofold. The viability of HBMECs was higher than 86%, suggesting a high biocompatibility of MA-TX-ETP-SLNs. Moreover, the efficiency in antiproliferation against U87MG cells was in the order of MA-TX-ETP-SLNs  >  TX-ETP-SLNs  >  ETP-SLNs  >  SLNs. The capability of MA-TX-ETP-SLNs to target HBMECs and U87MG cells during internalization was verified by immunochemical staining of expressed melanotransferrin. MA-TX-ETP-SLNs can be a potent pharmacotherapy to deliver ETP across the BBB to GBM.