title: Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma.
abstract: Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: (i) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial cells and tumor cells, (ii) conjugation of this homing peptide with a proapoptotic peptide that acts on mitochondria, and (iii) multivalent presentation on iron oxide nanoparticles, which enhances the proapoptotic activity. The iron oxide component of the nanoparticles enabled imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the nanoparticles eradicated most tumors in one GBM mouse model and significantly delayed tumor development in another. Coinjecting the nanoparticles with a tumor-penetrating peptide further enhanced the therapeutic effect. Both models used have proven completely resistant to other therapies, suggesting clinical potential of our nanosystem.
authors.affiliation: Center for Nanomedicine, Sanford-Burnham Medical Research Institute, University of California, Santa Barbara, CA 93106-9610, USA.
authors.forename: Lilach
authors.initials: L
authors.lastname: Agemy
authors.forename: Dinorah
authors.initials: D
authors.lastname: Friedmann-Morvinski
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.forename: Lise
authors.initials: L
authors.lastname: Roth
authors.forename: Kazuki N
authors.initials: KN
authors.lastname: Sugahara
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Girard
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mattrey
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D058185:Magnetite Nanoparticles; D009842:Oligopeptides