title: Self-assembled 20-nm (64)Cu-micelles enhance accumulation in rat glioblastoma.
abstract: There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers. While the circulation half-life of the 3HM was similar to 110-nm PEGylated liposomes (t1/2=15.5 and 16.5h, respectively), the 20-nm micelles greatly enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous injection. After accounting for tumor blood volume, the extravasated nanoparticles were quantified from the PET images, yielding ~0.77%ID/cm(3) for the micelles and 0.45%ID/cm(3) for the liposomes. For GBM lesions with a volume greater than 100mm(3), 3HM accumulation was enhanced both within the detectable tumor and in the surrounding brain parenchyma. Further, the nanoparticle accumulation was shown to extend to the margins of the GBM xenograft. In summary, 3HM provides an attractive nanovehicle for carrying treatment to GBM.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.
authors.forename: Jai Woong
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Department of Materials Science & Engineering, University of California, Berkeley, Berkeley, CA, United States.
authors.forename: JooChuan
authors.initials: J
authors.lastname: Ang
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mahakian
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tam
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.
authors.forename: Brett
authors.initials: B
authors.lastname: Fite
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Ingham
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Janine
authors.initials: J
authors.lastname: Beyer
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States.
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
authors.affiliation: Department of Materials Science & Engineering, University of California, Berkeley, Berkeley, CA, United States.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States. Electronic address: kwferrara@ucdavis.edu.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001810:Blood Volume; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008823:Micelles; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D049268:Positron-Emission Tomography; D051381:Rats; D014018:Tissue Distribution
chemical_list: D003301:Copper Radioisotopes; D008081:Liposomes; D008823:Micelles
keywords: BBB; Blood brain barrier; Drug delivery; Glioblastoma; Liposome; Micelles; Nanoparticle; PET; PET/MR; Positron emission tomography