title: Enhanced delivery of etoposide across the blood-brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles.
abstract: 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.
authors.affiliation: a Department of Chemical Engineering , National Chung Cheng University , Chia-Yi , Taiwan , Republic of China.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: a Department of Chemical Engineering , National Chung Cheng University , Chia-Yi , Taiwan , Republic of China.
authors.forename: I-Hsin
authors.initials: IH
authors.lastname: Wang
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005047:Etoposide / Q000008:administration & dosage* / Q000494:pharmacology; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D013629:Tamoxifen / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C000599356:MELTF protein, human; D008562:Membrane Glycoproteins; D013629:Tamoxifen; D005047:Etoposide
keywords: Blood–brain barrier; etoposide; glioblastoma multiforme; melanotransferrin; tamoxifen solid lipid nanoparticle